Eculizumab - Alexion AstraZencea Rare Disease
Alternative Names: 5G1-1; 5G1.1; Anti-C5 monoclonal antibody 5G1-1; h5G1.1; Monoclonal antibody 5G1-1; SolirisLatest Information Update: 28 Mar 2024
At a glance
- Originator Alexion Pharmaceuticals
- Developer Alexion AstraZeneca Rare Disease; Alexion Pharmaceuticals; Brigham and Womens Hospital; Handok Inc
- Class Anti-inflammatories; Antiallergics; Antianaemics; Antiasthmatics; Antihypertensives; Antipsoriatics; Antirheumatics; Eye disorder therapies; Monoclonal antibodies; Neuroprotectants; Skin disorder therapies; Urologics
- Mechanism of Action Complement C5 inhibitors
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Orphan Drug Status
Yes - Paroxysmal nocturnal haemoglobinuria; Delayed graft function; Neuromyelitis optica; Transplant rejection; Haemolytic uraemic syndrome; Myasthenia gravis; Dermatomyositis; Membranous glomerulonephritis
Orphan designation is assigned by a regulatory body to encourage companies to develop drugs for rare diseases.
- New Molecular Entity Yes
Highest Development Phases
- Marketed Haemolytic uraemic syndrome; Myasthenia gravis; Neuromyelitis optica; Paroxysmal nocturnal haemoglobinuria
- Phase III Delayed graft function; Guillain-Barre syndrome
- Phase II Preeclampsia; Renal transplant rejection
- No development reported Antiphospholipid syndrome; COVID-19 pneumonia; Heart transplant rejection; SARS-CoV-2 acute respiratory disease
- Discontinued Adult respiratory distress syndrome; Age-related macular degeneration; Allergic asthma; Autoimmune haemolytic anaemia; Bullous pemphigoid; Dermatomyositis; Glomerulonephritis; Idiopathic thrombocytopenic purpura; Lupus nephritis; Membranous glomerulonephritis; Motor neuron disease; Psoriasis; Rheumatoid arthritis; Systemic lupus erythematosus
Most Recent Events
- 28 Mar 2024 No recent reports of development identified for clinical-Phase-Unknown development in COVID-19 pneumonia in France (IV)
- 28 Mar 2024 No recent reports of development identified for clinical-Phase-Unknown development in COVID-19 pneumonia in USA (IV)
- 28 Mar 2024 No recent reports of development identified for clinical-Phase-Unknown development in SARS-COV-2 acute respiratory disease in France (IV)
Development Overview
Introduction
Eculizumab is a first-in-class, long-acting, humanised anti-C5 antibody developed by Alexion AstraZeneca Rare Disease (a subsidiary of AstraZeneca) for the treatment of COVID-19 pneumonia and SARS-COV-2 acute respiratory distress syndrome , delayed graft function, Guillain-Barre syndrome, haemolytic uraemic syndrome, myasthenia gravis, neuromyelitis optica, paroxysmal nocturnal haemoglobinuria, renal transplant rejection, and preeclampsia. Eculizumab binds to C5 complement to block the progression of the complement cascade. By binding to C5, eculizumab prevents the generation of the potent anaphylatoxin C5a and the cytolytic C5b-9 complex, or membrane attack complex. Eculizumab has been launched for the treatment of paroxysmal nocturnal haemoglobinuria haemolytic uraemic syndrome (aHUS), myasthenia gravis and neuromyelitis optica and paroxysmal nocturnal haemoglobinuria in Argentina, Australia, Austria, Belgium, Canada, Czech Republic, Denmark, European Union, Finland, France, Germany, Ireland, Israel, Italy, Japan, Luxembourg, Mexico, Netherlands, New Zealand, Norway, Poland, Portugal, Russia, South Korea, Spain, Sweden, Switzerland, Taiwan the USA and the United Kingdom. Eculizumab is approved in China for the treatment of neuromyelitis optica. Eculizumab is approved in the EU, Norway, Liechtenstein and Iceland for the treatment of neuromyelitis optica and myasthenia gravis. The candidate is launched in Japan for myasthenia gravis. The candidate is approved in China for myasthenia gravis, paroxysmal nocturnal haemoglobinuria and haemolytic uraemic syndrome . Clinical development is underway for delayed graft function, Guillain Barre syndrome, myasthenia gravis, neuromyelitis optica, haemolytic uraemic syndrome and renal transplant rejection in several countries. Clinical development for preeclampsia is underway in the US. An expanded access programme for COVID-19 infections including COVID-19 pneumonia and SARS-COV-2 acute respiratory distress syndrome is underway in France and the US.
Several clinical trials had been initiated by independent investigators for the indications of age-related macular degeneration, dense deposit disease (type II membranoproliferative glomerulonephritis (rendered as glomerulonephritis in the development table), and multifocal motor neuropathy (rendered as motor neuron disease in the development table). These programmes were no longer included in Alexion's development pipeline as of February 06, 2015, and therefore appear to have been discontinued.
The short-acting version of humanised anti-C5 antibody is called pexelizumab [see AdisInsight drug profile800010238].
As at November 2017, no recent reports of development had been identified for preclinical development in heart-transplant-rejection in the US.
In July 2021, Alexion Pharmaceuticals was acquired by AstraZeneca and changed its name to Alexion AstraZeneca Rare Disease [1] .
As at March 2024, no recent reports of development had been identified for clinical-Phase-Unknown development in COVID-19 pneumonia in USA (IV), France (IV), clinical-Phase-Unknown development in SARS-COV-2 acute respiratory disease in USA (IV), France (IV).
Company Agreements
In 2016, Handok extended its marketing partnership with Alexion Pharmaceuticals (now Alexion AstraZeneca Rare Disease), by extending the contract for eculizumab, and also the sales of asfotase alfa and sebelipase alfa. Earlier, in 2009, the two companies had entered into a partnership for the marketing of eculizumab in Korea, which is a treatment for paroxysmal nocturnal haemoglobinuria and haemolytic uraemic syndrome. [2] [1]
Alexion's Form 10-K (filed 17 February 2011) reported that Alexion entered into a licence agreement with the Medical Research Council (MRC) whereby MRC granted Alexion worldwide non-exclusive rights to certain patents related to the humanisation and production of monoclonal antibodies. Alexion will pay MRC royalties with respect to sales of eculizumab. The royalty is payable until the expiry of the last patents covered by the licence agreement, which is expected to be in 2015.
In July 2015, Alexion Pharmaceuticals had expanded the existing long-term commercial manufacturing and large-scale product supply agreement for eculizumab with Lonza Biologics, which was first signed in January 2003. Specific terms of the agreement were not disclosed [3] [4] .
Alexion signed an agreement with GTC Biotherapeutics in 2000 for the production of eculizumab in transgenic goats. However, this agreement no longer appears to be active.
Key Development Milestones
Age-related macular degeneration
A phase II trial of intravenously infused eculizumab for the treatment of non-exudative age-related macular degeneration was conducted by the University of Miami; Alexion Pharmaceuticals appeared to be a collaborator (COMPLETE; NCT00935883). However, in its Form 10-K (filed 06 February 2015), Alexion did not list this programme among its active clinical programmes, indicating that development for age-related macular degeneration has been discontinued.
Alexion Pharmaceuticals was developing an intravitreal formulation of eculizumab for the treatment of age-related macular degeneration. According to Alexion's pipeline, it appears the new formulation of eculizumab has completed phase I clinical development.
Allergic asthma
The asthma indication was not mentioned for eculizumab in Alexion's list of clinical programmes in the company's Form 10-K (filed 23 February 2010). Development for this indication appears to have been discontinued.
Intravenous and nebulised formulations of eculizumab were being investigated for the treatment of asthma. A randomised, double-blind, placebo-controlled, crossover phase II trial of intravenously infused eculizumab was completed in late 2008 for the prevention of mild allergic asthma (C07-002; NCT00485576). A total of 21 patients were enrolled at two sites in Canada [5] .
A surrogate anti-C5 monoclonal antibody of eculizumab was effectively delivered to the lungs and showed favourable results in preclinical models of acute severe allergic asthma. The data also indicated that such anti-C5 antibodies could be successfully aerosolised for therapeutic use [6] [7] .
COVID-19 pneumonia and SARS-COV-2 acute respiratory disease
In September 2021, Alexion Pharmaceuticals completed an Expanded Access Protocol under which patients with COVID-2019 infections had access to eculizumab (ECU-COV-402; NCT04802083). The EAP was initiated in March 2021 for the patients with a clinical presentation consistent with COVID-19 associated organ injury who received upto seven infusions of the drug over approximately four weeks [8] .
As of March 2021, Alexion Pharmaceuticals completed an emergency Expanded Access Programs (EAP) in the France and in the US (ECU-COV-401; NCT04355494). The programme was initiated in April 2020 in participants with severe COVID-2019 infection related penumonia, acute lung injury or acute respiratory distress syndome to be treated with eculizumab [9] [10] .
In March 2020, Alexion reported that they provided eculizumab to patients with COVID-2019 infections and severe pneumonia as an experimental emergency treatment. The company contacted Biomedical Advanced Research and Development Authority (BARDA) office, the Department of Defense (DoD) to discuss potential use of eculizumab in patients with COVID-2019 infections [11] .
Glomerulonephritis
In June 2015, the UK's NICE published a summary on the off-label use of eculizumab for the treatment of dense deposit disease (type II membranoproliferative glomerulonephritis [different to membranous glomerulonephritis]). The summary specifically suggests the use of eculizumab to prevent the recurrence of dense deposit disease [12] .
Independent investigators were conducting phase II development of eculizumab for the treatment of dense deposit disease in collaboration with Alexion. However, in the company's Form 10-K filed 06 February 2015, this programme was no longer listed.
Gullain Barre Syndrome
In June 2020, Japan's Ministry of Health, Labour and Welfare granted SAKIGAKE designation for eculizumab in Gullain Barre Syndrome [13] .
In August 2022, Alexion Pharmaceuticals completed a phase III trial which was designed to evaluate the efficacy and safety of eculizumab with concomitant intravenous immunoglobulin G (Ig) therapy as per standard of care in patients with severe Guillain-Barre syndrome (GBS) (ECU-GBS301; NCT04752566). The placebo-controlled, double-blind, randomised trial was initiated in February 2021 and enrolled 57 patients in Japan. As of May 2021, patient dosing in the trial is underway [14] [15] .
In November 2016 Chiba University, in collaboration with Alexion Pharmaceuticals, completed a phase II trial that assessed the safety and efficacy of eculizumab in patients with Gullain Barre Syndrome (100069; NCT02493725; UMIN000018171). The randomised, double-blind, placebo-controlled trial was initiated in July 015 and enrolled 34 patients in Japan [16] .
Haemolytic uraemic syndrome (HUS)
Before August 2023, Alexion Pharmaceuticals received approval in China for the treatment of haemolytic uraemic syndrome [17] .
In May 2014, regular approval for eculizumab was granted by the US FDA under a sBLA for the treatment of adult and paediatric patients with a treatment of atypical haemolytic uraemic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy. The full approval was granted based on the two-year outcome data from two additional long-term prospective clinical trials. The revised label specifies longer term clinical benefit associated with sustained treatment with eculizumab and the use of eculizumab prior to the use of supportive care with either plasma exchange or plasma. Eculizumab was initially approved by the US FDA for aHUS in children and adults, in September 2011, under an accelerated approval process. This was the first FDA-approved product for the treatment of aHUS. The new indication was approved with an extension of the existing Risk Evaluation and Mitigation Strategy [18] [19] [20] .
Alexion received a positive opinion from the CHMP for an updated EU label to include data on the benefits of long-term treatment and the risks associated with treatment discontinuation in patients with atypical haemolytic uraemic syndrome, in February 2015. The data in support of this label change included results of the M11-001 trial [21] . Eculizumab was granted a centralised EU marketing authorisation by the EMA for the treatment of aHUS in children and adults, in November 2011 [22] [23] [24] . Alexion had submitted the marketing applications for eculizumab in the treatment of aHUS to the FDA and the EMA in April 2011 [25] . The US and EU submissions included results from two 26-week phase II trials in adults and adolescents with aHUS. Both trials met their primary endpoints and positive final data was published in the New England Journal of Medicine [26] [27] .
In the UK (where the drug is available for the treatment of aHUS), there was controversy over whether eculizumab should be used, after the Ministers of Health decided not to follow a positive recommendation issued by the Advisory Group for National Specialised Services (AGNSS). AGNSS was set up by the UK Government to evaluate therapies for patients with very rare disorders. The decision not to follow the recommendation of AGNSS was made in January 2013, approximately a year and a half after the European Commission issued approval for this indication. The UK Ministers of Health referred consideration of the drug for this indication to the National Institute for Health and Clinical Excellence (NICE) [28] . The National Health Service (NHS) in the UK made eculizumab available on an interim basis, pending the results of appraisal by the NICE. In March 2014, the NICE issued draft guidance (produced by its Highly Specialised Technologies programme) concerning use of eculizumab for the treatment of aHUS. The agency accepted that eculizumab is an effective treatment for aHUS, but asked Alexion to explain the high cost of the drug. NICE estimated that routine use of eculizumab would cost the NHS approximately £58 million in the first year; the cost over 5 years is estimated at more than £80 million. The independent advisory committee of NICE requested clarification from Alexion concerning the manufacturing and research and development costs of a medicine for a very rare condition, and also asked NHS England to clarify treatment costs for a highly specialised technology. The information obtained in response to this request was discussed in April 2014 at a meeting of the Evaluation Committee [29] [30] . In September 2014, NICE reaffirmed its earlier positive assessment on eculizumab for the treatment of aHUS and issued a recommendation that it be nationally commissioned for patients with aHUS, but subject to certain conditions. These conditions included the establishment of a centre to coordinate the use of eculizumab, and monitoring systems to record patients diagnosed with the disease [31] . A final draft guidance from NICE was issued in November 2014, under which eculizumab was recommended for commissioning for all patients in England with aHUS [32] [33] . NICE issued final guidance in January 2015, recommending eculizumab for the treatment of aHUS. This is the first guidance to be issue under NICE's Highly Specialised Technologies programme for very rare conditions [34] .
Handok launched eculizumab for atypical haemolytic uraemic syndrome in Korea, in 2012 [2] .
In September 2013, the Ministry of Health, Labour and Welfare in Japan approved the use of eculizumab for the treatment of all patients with aHUS [35] .
Alexion announced in March 2013 that Health Canada has approved eculizumab for use in adolescents and adults with aHUS to inhibit complement-mediated thrombotic microangiopathy. The agency has also approved eculizumab for use in paediatric patients with aHUS, under the Notice of Compliance with Conditions (NOC/c) policy (based on retrospective data). In fulfilment of the required conditions, Alexion will conduct an additional prospective study in paediatric patients with aHUS and will provide further data from all continuing and future trials of the drug in patients with aHUS [36] .
In April 2012, Alexion initiated a phase IV trial to asses the post-marketing safety and disease progression of eculizumab in patients with atypical haemolytic uraemic syndrome (M11-001; NCT01522183). The observational trial was conducted in 2 000 patients in the US [37] .
In July 2023, Alexion initiated the Soliris phase IIIb trial to evaluate the efficacy, safety, pharmacokinetics, pharmacodynamics, and immunogenicity of eculizumab in complement inhibitor treatment-naïve paediatric and adult patients with atypical hemolytic uremic syndrome (aHUS) (NCT05876351; D7413C00001). The prospective, single-arm, multicenter study intends to enrol approximately 25 patients in China [38] .
In September 2013, Alexion completed a phase II trial that characterised the overall safety and tolerability of eculizumab in patients with atypical haemolytic uraemic syndrome (C11-005J; NCT01757431). The open-label trial was initiated in May 2012, and enrolled two patients in Japan [39] .
In August 2009, Alexion commenced enrolment in four open-label pivotal phase II trials of eculizumab in patients with aHUS from sites in North America and Europe (C08-003 A/B NCT00838513, NCT00844428; C08-002A/B NCT00844545, NCT00844844). NCT00844844 and NCTNCT00844545 trials were completed in July 2013 and enrolled plasma therapy-resistant patients with atypical haemolytic uraemic syndrome. NCT00844428 and NCT000838513 trials were completed in December 2013 and enrolled plasma therapy-sensitive patients with aHUS [40] [41] [42] [43] . Enrolment of patients in all four trials was completed in April 2010; in total, 37 adult and adolescent patients with aHUS were enrolled in these trials [44] [45] . In June 2014, Alexion Pharmaceuticals released data from three subgroup analysis from prospective clinical trials and survival model data from a registrational trial [46] .
In February 2014, an additional phase II trial in adults with aHUS was completed in the US, Belgium, France, Germany, Italy, Spain and the UK (C10-004; NCT01194973). The open-label trial was initiated in July 2010 and enrolled 41 patients. In December 2014, Alexion presented post-hoc analysis data from the C10-004 and C10-003 phase II trials at the 56th Annual Meeting of the American Society of Haematology (ASH-2014). The pooled data of these two trials demonstrated that, eculizumab treatment significantly improved the haematologic and renal parameters in adults and paediatric patients, regardless of genetic mutation, with no unexpected safety concerns [47] . Alexion has reported 26-week and one year data from this trial. Data from subgroup analysis and combined analysis with C10-003 trial have also been reported [48] [49] [50] .
A phase II trial investigated the efficacy and tolerability of eculizumab in 22 paediatric aHUS patients. Patients were recruited from centres in the US, Canada, and the EU (C10-003; NCT01193348). Results were reported in November 2013. Alexion has reported efficacy and safety data from a subgroup analysis [48] [49] [45] [51] .
In June 2011, Alexion initiated a phase II open-label trial of eculizumab in Germany for the treatment of patients with Shiga-toxin producing E. coli haemolytic uraemic syndrome (STEC-HUS), resulting from a recent enterohaemorrhagic E. coli (EHEC) outbreak. Alexion had been supplying eculizumab throughout the crisis, which started in May 2011. The purpose of the trial is to provide the therapy in a controlled manner and to collect data systematically, which could be useful to treat STEC-HUS in the future. All patients receiving eculizumab in the STEC-HUS outbreak were to be included in the trial, which was authorised by the German regulatory authorities [52] . Dosing in the trial was completed in the first quarter of 2012. Positive 8-week (primary endpoint) and 28-week efficacy data have been reported [53] [54] [55] [56] . Alexion reported in July 2013 that it had obtain and analysed longer-term control clinical outcome data from the epidemiology study in approximately 400 patients with STEC-HUS who received only the best supportive care during the German epidemic [57] . In October 2013, Alexion Pharmaceuticals stated that it continue to analyse longer-term control clinical outcome data from this study [58] . Eculizumab is not indicated for the treatment of patients with STEC-HUS.
In August 2009, the European Commission granted Alexion Pharmaceuticals' eculizumab orphan drug status in the treatment of aHUS [59] . Eculizumab also obtained orphan drug status in the EU for the treatment of infection-associated HUS, such as STEC-HUS. The FDA has granted eculizumab orphan drug status for the treatment of aHUS and STEC-HUS.
Haemolytic anaemias and antiphospholipid syndrome
Alexion has tested eculizumab in a patient with autoimmune haemolytic anaemia (also known as cold agglutinin disease or CAD); a disease characterised by autoimmune attacks on red blood cells, leading to severe complement activation and haemolysis, anaemia and poor quality of life. Eculizumab treatment was associated with reduced haemolysis, absence of the need for blood transfusions, and improved symptoms of fatigue and anaemia. As of June 2013, Alexion has continued to mention CAD among its development programmes for eculizumab, which was underway as an investigator-initiated clinical trial. However, in the company's Form 10-K filed 06 February 2015, this programme was no longer listed.
Alexion was also developing a clinical programme to investigate the use of eculizumab for the treatment of catastrophic antiphospholipid syndrome (CAPS), a disorder in which uncontrollable blood clotting often leads to multiple organ failure; however, no recent development has been reported [60] [61] .
Heart transplant rejection
Alexion reported on its pipeline that eculizumab was in preclinical development for the prevention of heart transplant rejection. However, it is unclear whether development is ongoing as this indication was not present on Alexion's Form 10-K (filed 17 February 2011).
Membranous glomerulonephritis
Alexion completed a phase II efficacy study with eculizumab in 115 non-lupus patients with membranous glomerulonephritis in the US. In February 2002, Alexion commenced dosing in a follow-on open-label extension of the phase II study. However, Alexion discontinued development in this indication in order to focus its resources on development for paroxysmal nocturnal haemoglobinuria.
The FDA granted eculizumab fast-track designation in membranous glomerulonephritis in early 2000 and the drug has orphan drug status in the US for idiopathic membranous glomerular nephropathy.
Motor neuron disease
Independent investigators were conducting a phase II trial of eculizumab for the treatment of multifocal motor neuropathy, in collaboration with Alexion. However, in the company's Form 10-K filed 06 February 2015, this programme was no longer listed.
Myasthenia gravis
In August 2023, AstraZeneca announced the launch of eculizumab (Soliris®) in Japan. In the same month Japanese Ministry of Health, Labour and Welfare (MHLW) approved drug for the treatment of children and adolescents with gMG in Japan.The approval by the Japanese Ministry of Health, Labour and Welfare (MHLW) was based on results from the Phase III trial of Soliris in paediatric patients with refractory gMG [17] .In December 2017, Alexion announced that the Ministry of Health, Labour and Welfare (MHLW) in Japan approved eculizumab (Soliris®) for the treatment of patients with gMG, who are AChR antibody-positive and whose symptoms are difficult to control with high-dose intravenous immunoglobulin therapy or plasmapheresis [62] . In June 2017, MHLW accepted for review Alexion's sNDA, filed in March 2017, to extend the indication for eculizumab as a treatment of AChR antibody-positive gMG patients. The application was based on the results from the phase III REGAIN study [see below] [63] [64] .
In October 2017, the US FDA approved eculizumab (Soliris®) as a treatment for adult patients with generalised myasthenia gravis (gMG), who are anti-acetylcholine receptor (AchR) antibody-positive [65] . In March 2017, the US FDA accepted Alexion's sBLA to extend the indication for eculizumab as a treatment of anti-acetylcholine receptor (AChR) antibody-positive refractory generalised myasthenia gravis patients and assigned a PDUFA date. The application was submitted to the US FDA in January 2017. The submission is supported by the comprehensive data from the phase III REGAIN study [see below] [66] [67] [68] .
In August 2017, the European Commission approved the use of eculizumab for the treatment of refractory generalised myasthenia gravis (gMG) in patients who are anti-acetylcholine receptor (AChR) antibody-positive [69] . In June 2017, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion for the approval. The submission was completed in January 2017 and was based on comprehensive data from the phase III REGAIN study [63] [67] [68]
In June 2023, eculizumab has been approved in China for the treatment of adult patients with refractory generalised myasthenia gravis (gMG). The approval by the National Medical Products Administration (NMPA) in China was based on comprehensive results from the phase III REGAIN trial [70] . As of July 2022, AstraZeneca submitted regulatory submission to China's National Medical Products Administration for the approval of eculizumab in the treatment of generalised myasthenia gravis (gMG) [71] .
In July 2023, AstraZeneca received approval for eculizumab in the EU for children and adolescents with refractory generalised myasthenia gravis (gMG) [72] . In June 2023, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the marketing authorization under expanded use of eculizumab for the treatment of refractory generalised myasthenia gravis (gMG) in children and adolescents aged six to 17 years who are anti-acetylcholine receptor (AChR) antibody-positive (Ab+). The positive opinion was based on results from the phase III trial in paediatric patients with refractory gMG [see below]. Earlier in June 2023, Alexion and AstraZeneca submitted a Marketing Authorization Application (MAA) to the EU for expanded use of eculizumab treatment of refractory generalised myasthenia gravis (gMG) in children and adolescents aged six to 17 years who are anti-acetylcholine receptor (AChR) antibody-positive (Ab+) [73] .
In November 2023, Alexion Pharmaceuticals completed a pivotal phase III trial which was designed to investigate the efficacy, safety, pharmacokinetics, and pharmacodynamics of eculizumab, in paediatric patients with refractory generalised myasthenia gravis (P200-2018; ECU-MG-303; EudraCT2016-001384-37; NCT03759366). The trial was initiated in December 2018, and intended to enroll 11 patients in the US, Germany, Netherlands and Japan. Change from baseline in the Quantitative Myasthenia Gravis (QMG) score over time irrespective of rescue treatment will be assessed as the primary endpoint [74] . In April 2023, results from the study were presented at the 75th Annual Meeting of the American Academy of Neurology (AAN-2023) [75] . In June 2023, updated adverse events data from the trial were released by AstraZeneca [73] .
According to top-line results released by Alexion in June 2016, the phase III REGAIN trial failed to meet its primary efficacy endpoint, however, there were clinically meaningful improvements in MG-ADL and QMG measures in patients treated with eculizumab compared with placebo [76] . New secondary efficacy endpoint results were released by Alexion Pharmaceuticals in July 2016 [77] . Alexion, in December 2013, initiated the randomised, double-blind, placebo-controlled, pivotal phase III trial, to assess the efficacy and safety of eculizumab in patients with refractory generalised myasthenia gravis (REGAIN; ECU-MG301; NCT01997229; EudraCT2013-003589-15) (Alexion Pharmaceuticals, 10-Q filed in July 2015). The global trial enrolled 125 patients in the US, Canada, Japan, Sweden, Italy, Denmark, Spain, UK, Belgium, Germany, the Netherlands, Greece, South Korea, Turkey, Hungary, France, Czech Republic, Brazil, Australia and Finland. The company further reported that it had exceeded the target enrolment in the REGAIN phase III trial. The trial was completed in June 2016 [78] [79] [57] [80] [81] . In March 2019, Alexion completed an open-label extension phase III trial that evaluated the long-term safety and efficacy of eculizumab in patients with refractory generalised myasthenia gravis (ECU-MG302; EudraCT2013-002191-41; NEUR3784; NCT02301624). The open-label trial was initiated in October 2014, and enrolled 117 participants in Italy, the UK, Belgium, Germany, Sweden, Hungary, Spain, the Netherlands, Denmark, Czech Republic, and Finland. Earlier, in September 2017, interim efficacy results from the extension trial were released by the company [82] [83] . Additional interim results were presented by the company at the 71st Annual Meeting of the American Academy of Neurology (AAN-2019) [84] .
A randomised, double-blind, cross-over phase II trial was initiated by Alexion in October 2008 to determine whether eculizumab is safe and effective in the treatment of patients with myasthenia gravis when combined with various immunosuppressants, such as prednisone, methotrexate, mycophenolate mofetil, ciclosporin and cyclophosphamide (NCT00727194). Patients with moderate to severe muscle weakness despite previous treatment will receive weekly intravenous eculizumab at 600mg for four doses, followed by a 900mg dose every two weeks for seven doses in the first treatment period (16 weeks), followed by corresponding placebo treatment (16 weeks), or patients will receive the reverse sequence (i.e. placebo in the first treatment period, followed by eculizumab in the second); washout period between treatments is 5 weeks. Primary efficacy will be evaluated by adverse event profiles and Quantitative Myasthenia Gravis (QMG) score. Enrolment of 14 patients in the US, Canada, and UK has been completed and results have been released [55] [85] .
In August 2014, the European Commission granted orphan drug status to eculizumab for the treatment of myasthenia gravis in the EU [86] . Eculizumab was granted orphan drug designation by the US FDA in June 2014 for the treatment of myasthenia gravis [87] . Eculizumab was also granted orphan drug designation in Japan for the treatment of myasthenia gravis [88] .
Collaborative preclinical studies conducted with researchers at Case Western Reserve University demonstrated that a surrogate anti-C5 antibody prevented experimentally acquired myasthenia gravis and inhibited progression of disease in two thirds of the rodents evaluated.
Neuromyelitis optica (NMO)
In October 2023, Soliris approved in China for the treatment of adults with neuromyelitis optica spectrum disorder (NMOSD) [89]
In June 2019, the U.S. Food and Drug Administration approved the sBLA for eculizumab for the treatment of patients with neuromyelitis optica spectrum disorder who are Anti-Aquaporin-4 (AQP4) antibody positive [90] . In February 2019, US FDA accepted the supplemental Biologics License Application (sBLA) and ganted priority review [91] . The sBLA was submitted based on the results from the phase III PREVENT study [see below] [92] .
In November 2019, the Ministry of Health, Labour and Welfare in Japan approved the extension of the current marketing authorization of eculizumab to include the prevention of relapse in patients with anti-aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD), including neuromyelitis optica. The approval was based on results from the phase III PREVENT study [see below]. Prior to April 2019, an application seeking approval was submitted by Alexion Pharmaceuticals in Japan [93] [94] .
In August 2019, the European Commission approved the extension of the current marketing authorization of eculizumab for the treatment of neuromyelitis optica spectrum disorder in adults [95] . Earlier, in July 2019, the Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion to extend the current marketing authorization of eculizumab to include the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive with a relapsing course of the disease. The European Commission will review the CHMP opinion and the final decision is planned within two months [96] . In February 2019, Alexion Pharmaceuticals submiited regulatory application in the European Union for the approval of eculizumab for the treatment of neuromyelitis optica spectrum disorder, in the US. The submission was based on the results from the phase III PREVENT study [see below] [92] .
In June 2013, eculizumab received orphan drug designation from the US FDA for the treatment of neuromyelitis optica [97] . The Committee for Orphan Medicinal Products of the European Medicines Agency issued a positive opinion for eculizumab in the treatment of neuromyelitis optica in July 2013. The recommendation for orphan designation was to be considered by the European Commission for final approval [98] . Orphan designation for eculizumab in NMO was subsequently granted by the European Commission in August 2013 [79] . Eculizumab was granted orphan drug designation for this indication in Japan in November 2014 [99] .
In April 2021, Alexion Pharmaceuticals presented pooled long-term safety and efficacy data from the phase III PREVENT trial and its open label extension trial (OLE) [See below] at 73rd Annual Meeting of the American Academy of Neurology (AAN-2021) [100] . Pooled long-term efficacy and safety data from the phase III PREVENT and ECU-NMO-302 trials [see below] were presented at the 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-2019), in September 2019. Updated safety data from the pooled analysis were presented at the 72nd Annual Meeting of the American Academy of Neurology (AAN-2020), in April 2020 [101] [102] .
In September 2018, Alexion reported that the pivotal phase III PREVENT trial met its primary endpoint of time to first adjudicated on-trial relapse, demonstrating that treatment with eculizumab reduced the risk of NMO relapse. Based on the positive results of the trial the company intends to file regulatory applications in the US, EU, and Japan [103] . In June 2019 Alexion terminated phase III PREVENT trial which evaluated the efficacy and safety of eculizumab as compared with placebo in participants with neuromyelitis optica spectrum disorder (NMOSD) who were anti-aquaporin-4 (AQP4) antibody-positive (NCT01892345; ECU-NMO-301). The randomised trial was initiated in April 2014 and enrolled 143 patients in the US, Australia, Canada, Croatia, Colombia, Czech Republic, Denmark, France, Germany, Hong Kong, Italy, Japan, Malaysia, South Korea, Russia, Singapore, Spain, Taiwan, Turkey, the UK, Argentina, Austria and Thailand. In March 2020, data from the trial were presented at the 72nd Annual Meeting of the American Academy of Neurology (AAN-2020). Positive results from the trial were released by Alexion Pharmaceuticals in May 2019. In October 2021, data from the trial were presented at the 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-2021) [104] [105] [106] [107] [108] [109] [110] .
In July 2021, Alexion Pharmaceuticals completed an open-label extension (OLE) phase III trial that investigated the long-term safety and efficacy of eculizumab in patients with relapsing neuromyelitis optica spectrum disorder (ECU-NMO-302; NCT02003144; EudraCT2013-001151-12). The open-label trial was initiated in January 2015, and enrolled 119 patients in the US, Austria, France, Australia, Argentina, Canada, Colombia, Croatia, Czech Republic, Denmark, Germany, Hong Kong, Italy, Japan, Malaysia, South Korea, Russia, Spain, Taiwan, Thailand, Turkey, and the UK [111] .
In December 2019, Alexion Pharmaceuticals initiated a phase II/III trial to evaluate the safety and efficacy of eculizumab in pediatric participants (aged 2 to < 18 years) with relapsing neuromyelitis optica spectrum disorder (NCT04155424; ECU-NMO-303; EudraCT2019-001829-26). The open label trial intends to enrol approximately 15 patients in Japan, in the US, Canada, Italy, Spain, Germany and may be extends to South Korea [112] .
Results from an investigator-sponsored open-label phase I/II trial of eculizumab in patients with NMO were presented at the American Neurological Association Annual Meeting (ANA-2012) in October 2012 [113] . This trial was conducted by the Mayo Clinic and involved 14 patients (NCT00904826). In two of Alexion's Form 10-K filings (2010 and 2011) eculizumab was listed as being in phase II development for NMO [56] .
Paroxysmal nocturnal haemoglobinuria (PNH)
Before August 2023, AstraZeneca received approval in China for the treatment of paroxysmal nocturnal haemoglobinuria [17] .
Eculizumab was launched as Soliris® in the US after marketing approval was granted by the FDA in March 2007. The product is indicated for the treatment of all patients with PNH, but carries a boxed warning that eculizumab increases the incidence of meningococcal infections. The BLA submission and approval was based on data from the pivotal phase III TRIUMPH trial [114] [115] [116] [117] [118] .
The CHMP issued a positive opinion to update the indication for eculizumab to include treatment of paroxysmal nocturnal haemoglobinuria in patients with high disease activity regardless of history of transfusion, in February 2015. The filing was based on results of the M07-001 trial [21] . In June 2007, eculizumab received approval from the European Commission for the treatment of patients with PNH in the EU. The MAA was reviewed under the centralised procedure and was evaluated under an accelerated assessment procedure. Eculizumab was initially made available to patients in Europe on a named-patient basis while reimbursement, price approval and funding processes were being established. Alexion subsequently began commercial sales in select European markets during the fourth quarter of 2007. Furthermore, the British government notified Alexion in September 2008 that eculizumab was to qualify for reimbursement on national level, beginning in the second quarter of 2009 [119] [120] [115] . The EMA granted a positive opinion recommending unlimited validity for eculizumab in March 2012 [22] . In May 2013, the EMA's European public assessment report (EPAR) for Soliris® was amended to include treatment for both adults and children with PNH [121] .
The Japanese Ministry of Health, Labour and Welfare approved eculizumab for the treatment of PNH in April 2010. Approval was based on an NDA submitted by Alexion during April 2009, and which was supported by data from the phase III AEGIS trial. In June 2010, the company announced that the product will be launched in the third quarter of 2010, in the same month the product was granted reimbursement status through Japan's National Health Insurance system [122] [123] [124] [125] . An application for marketing authorisation for this indication has also been submitted in Switzerland; Alexion reported in its Form 10-K (filed 23 February 2010) that approval was granted in Switzerland in 2010. Approval was also granted in South Korea early in 2010.
Eculizumab was approved under priority review by Health Canada's Biologics and Genetic Therapies Directorate (BGTD) in January 2009 for the treatment of all patients with PNH. The marketing application contained data from the TRIUMPH, SHEPHERD and E05-001 trials [126] . Alexion launched eculizumab for the treatment of PNH in Canada in July 2009. Alexion Pharma Canada has also launched the OneSource™ Program, when a specific OneSource™ Case Manager gets assigned to a patient who enrols in the programme. The patient will receive an immediate and over time support, ranging from disease education to coordinated care with the Physician's office [127] .
In February 2009, eculizumab was also approved under priority review by the Therapeutic Goods Administration (TGA) in Australia for the treatment of all patients with PNH. A division of Alexion based in Sydney was working with Australian healthcare authorities to obtain reimbursement for the product and had expected to have a decision on pricing structure by the end of 2009 [128] .
Handok launched eculizumab for the treatment of paroxysmal nocturnal haemoglobinuria in Korea, in 2012 [2] .
Alexion Pharmaceuticals initiated an expanded access programme EMBRACE, for eculizumab, for the treatment of paroxysmal nocturnal haemoglobinuria in the US (C06-002; NCT00438789).
In July 2023, Alexion Pharmaceuticals in collaboration with AstraZeneca initiated a phase III trial to evaluate the efficacy, safety, pharmacokinetics, pharmacodynamics, and immunogenicity of eculizumab in complement inhibitor treatment naïve adult participants with paroxysmal nocturnal hemoglobinuria (PNH) in China (NCT05886244; D7414C00001). The single-arm, open-label, multicenter trial intends to enrol approximately 25 patients in China [129] .
In October 2008, Alexion Pharmaceuticals completed a phase III Soliris trial which evaluated the long-term safety of eculizumab in patients with transfusion dependent haemolytic paroxysmal nocturnal haemoglobinuria (E05-001; NCT00122317). This open-label extension trial (TRIUMPH, SHEPHERD or X03-001; see below) enrolled 187 patients in the US, Australia, Belgium, Canada, France, Germany, Ireland, Italy, the Netherlands, Spain, Sweden and the UK, and was initiated in May 2005 [130] .
Results from the phase III TRIUMPH trial (NCT00112983; EudraCT2004-000646-20) demonstrated that all primary and secondary endpoints were achieved with statistical significance [131] . This randomised, double-blind, placebo-controlled trial evaluated haemoglobin stabilisation and transfusion reduction efficacy and safety of eculizumab IV infusion in approximately 75 patients with PNH [132] .
Patient follow-up consultations in the phase III SHEPHERD trial were completed in October 2006 (NCT00122304; EudraCT2004-002795-42; C04-002). The open-label study, which was initiated in February 2005, conducted to collect additional safety data from eculizumab among haemolytic PNH patients who have undergone transfusion. A total of 85 patients received treatment for 12 months in the US, Australia, Belgium, Canada, France, Germany, Ireland, Italy, Netherlands, Spain, Sweden, Switzerland and the UK. Data presented by Alexion demonstrated that eculizumab therapy reduced haemolysis, and improved fatigue, quality of life and anaemia in a population of patients with minimal transfusion requirements and/or evidence of thrombocytopenia. Additionally, 1-year data showed that the trial met both its primary endpoints [133] [134] [135] [136] .
Patient enrolment in a single registration trial, known as AEGIS, was completed by Alexion in October 2008. The trial evaluated the safety, efficacy and pharmacology of eculizumab as a treatment for patients with PNH in Japan. The study was initiated in January 2008 after study approval was granted by the Pharmaceutical and Medical Device Administration (PMDA). A total of 29 patients will be dosed with eculizumab for 12 weeks after enrolment. The inclusion criteria for the AEGIS study was similar to those used in the previously conducted phase III, SHEPHERD study. Results have been reported and are consistent with earlier studies [137] [138] [139] .
In November 2011, Alexion Pharmaceuticals completed a phase I/II trial that investigated the appropriate dose regimens, pharmacokinetics, pharmacodynamics, safety and efficacy of eculizumab IV infusion in paediatric and adolescent patients (aged 2 to 17 years) with paroxysmal nocturnal haemoglobinuria (M07-005;EudraCT2009-010402-11; NCT00867932). The open-label, single-group, non-randomised trial was initiated in May 2009, and recruited seven patients in the US [140] .
Results presented at the European Haematology Association Congress 2009 demonstrated eculizumab to significantly reduce haemolysis in never-transfused patients with PNH and in patients with PNH and thrombocytopenia, showed sustained platelet recovery following treatment with eculizumab [141] .
A pilot, open-label phase Ib trial evaluating eculizumab in 11 patients with PNH has been completed in the UK. All patients in the trial chose to participate in two consecutive one year extension studies. One-year and 2-year cumulative results have been presented. The positive findings further supported further clinical development of eculizumab for PNH [142] [143] .
Eculizumab has been granted orphan drug status in the US, EU, Australia, Canada and Japan for the treatment of PNH [128] [137] [144] . According to Alexion's Form 10-K (filed 17 February 2011), eculizumab has also been granted orphan drug status in South Korea for the treatment of PNH.
Preeclampsia
In November 2023, Alexion Pharmaceuticals terminated the phase II CRUSH trial due to PI moved institutions. The trial had to determine if treatment with eculizumab prolongs pregnancy compared to historical controls in women with preeclampsia between 23-30 weeks gestation (STUDY00000039; NCT04725812). The single arm, open-label study initiated in September 2021 and enrolled 2 participants in the US [145] .
Renal transplant rejection
Eculizumab is in phase II development for the treatment of antibody mediated rejection (AMR) following renal transplantation, and prevention of AMR presensitised renal transplant (living and deceased donor) rejection (Alexion's 2014 annual report filed in February 2015).
In company-sponsored trials, Alexion was evaluating the effectiveness of eculizumab in preventing antibody mediated rejection (AMR), also known as acute humoral rejection (AHR), in patients undergoing kidney transplant. The clinical protocols for two trials were approved by the US FDA and EMA [146] . The company initiated a phase II living-donor study in November 2011 (NCT01399593). The study enrolled 102 patients in the US, Australia, the UK, France, Germany, Italy, the Netherlands, Norway, Sweden and Spain. The primary composite endpoint of Week 9 post-transplantation treatment failure rate did not reach statistical significance, according to results reported in January 2015; however, the trial was terminated in July 2016 [147] [148] . In May 2017, Alexion Pharmaceuticals completed a phase II deceased-donor study that assessed the safety and efficacy of eculizumab in the prevention of AMR in sensitised patients receiving deceased-donor kidney transplant (NCT01567085; EudraCT2010-019631-35; C10-002; 362145; ACTRN12612000333819). Interim results from this trial, reported in September 2013, suggested that the primary endpoint of 9-week treatment failure rate had been met. The trial was initiated in May 2012 and enrolled 80 patients in Australia, France, Italy, Spain, Sweden and the UK. In May 2015, positive results were reported from the study [149] [150] [151] [152] [153] [57] [154] [155] .
In June 2015, a investigator sponsored phase I/II trial investigating the safety and efficacy of eculizumab when added to conventional treatment was terminated due to poor enrolment (ABOi; NCT01095887). The phase I/II trial was initiated in March 2010, to evaluate the prevention of antibody-mediated rejection in ABO blood group incompatible living donor kidney transplantation in 6 patients enrolled at study centre in the US [156] . Another investigator-sponsored phase I/II trial by the Mayo Clinic investigating the addition of eculizumab to conventional anti-rejection treatment in kidney transplant patients was terminated in October 2017(NCT01106027; 09-005627DD). The trial was initiated in March 2010 and intended to enrol approximately 40 patients receiving positive cross-match deceased donor kidney transplant in the US [157] . Alexion is a collaborator in both these trials.
In August 2017, the Mayo Clinic completed a phase II trial that evaluated the safety and efficacy of a dosing regimen of eculizumab, when added to conventional therapy, in preventing antibody-mediated rejection (AMR) in positive cross-match living-donor kidney transplantation (NCT00670774; 07-007208). Eculizumab was given 1h pre-transplantation, then once-weekly for 4 weeks, and then again at weeks 5, 7 and 9. It was hypothesised that the blockade of terminal complement activation at the time of transplant, in combination with conventional treatment, will reduce the incidence of rejection. Alexion appeared to be a collaborator in this trial. The open-label trial enrolled 31 patients with anti-HLA antibodies specific to their living donor in the US [158] [122] .
The Brigham and Women's Hospital, in collaboration with Alexion, initiated a phase II trial in November 2013 to investigate the efficacy and tolerability of eculizumab versus plasmapheresis + immune globulin in approximately 21 patients with acute, grade II or grade III, antibody-mediated, renal transplant rejection (NCT01895127). However, the trial was terminated in April 2016 due to lack of efficacy [159] .
In April 2014, the European Commission granted orphan drug designation to eculizumab for the prevention of graft rejection following solid organ transplantation [160] .
At the American Transplant Congress in May 2009, Alexion presented early clinical and laboratory data on the potential role of terminal complement inhibition with eculizumab in the treatment of a subset of kidney transplant patients who are at high risk for antibody-mediated rejection [161] .
In a rodent model of transplantation, eculizumab induced inhibition of terminal complement and successfully prevented antibody mediated rejection. Furthermore, addition of anti-C5 antibody to standard anti-cellular therapy resulted in a significant increase in graft survival, compared with graft survival in animals treated with anti-cellular therapy alone. Eculizumab was also noted to prevent antibody mediated rejection even in the presence of high levels of circulating anti-donor antibodies.
Delayed-graft function (DGF)
In December 2016, Alexion released top-line results from the phase II/III PROTECT study showing that the trial did not meet its primary endpoint of incidence of delayed graft function, with a two-dose regimen of eculizumab, in patients with renal transplants (NCT02145182, EudraCT2013-004650-25, ECU-DGF201). Alexion completed the randomised, parallel-group, double-blind, placebo-controlled trial in November 2016. The trial was initiated in August 2014, and enrolled 286 patients in the US, Germany, Czech Republic, Canada, France, Italy, Australia and Spain [162] [163] [164] [152] [165] [57] [166] .
In May 2019, Alexion Pharmaceuticals in collaboration with Icahn School of Medicine at Mount Sinai terminated a double-blind, placebo-controlled, phase II pilot study that was designed to determine the safety and efficacy of eculizumab in the prevention of DGF following deceased-donor renal transplantation (NCT01403389). After interim analysis, the pilot study was terminated and modified to a larger multicenter study (NCT01919346) to better assess efficacy. The trial intended to enrol approximately 20 participants in the US (Alexion Form 2013 10-K) [167] .
An additional investigator-sponsored phase II trial of eculizumab for the prevention of DGF in renal transplantation was initiated in August 2013, in the US however, the study was discontinued in December 2017, based on results from Alexion PROTECT DGF study (NCT01919346). The trial was sponsored by Dr. P. Heeger of Icahn School of Medicine at Mount Sinai, with Alexion Pharmaceuticals as collaborator. The randomised, double-blind, placebo-controlled trial enrolled 21 patients. The primary outcome measure is need of at least one dialysis treatment in the first week following transplantation [168] .
In January 2014, eculizumab was granted orphan drug designation by the US FDA for the prevention of delayed graft function in renal transplant patients [165] . In February 2014, the European Commission granted eculizumab orphan drug designation for the prevention of DGF following solid organ transplantation [169] .
Rheumatoid arthritis
Preliminary results of a phase IIb trial in rheumatoid arthritis showed that monthly treatment with eculizumab caused a significant, moderate improvement in the ACR20 score over a 6-month period [170] . This trial, which was the first of two scheduled phase IIb trials of eculizumab in rheumatoid arthritis, enrolled 368 patients in the US and Canada. A 12-month open-label extension study of the phase IIb trial was in progress. However, Alexion discontinued development in this indication to focus its resources on development for paroxysmal nocturnal haemoglobinuria.
Phase I and II trials in rheumatoid arthritis had previously been completed.
The rationale behind evaluating eculizumab in this indication was that activated terminal complement proteins appear to have a central role in the pathogenesis of immune-mediated joint inflammation, indicating that anti-C5 monoclonal antibodies may have therapeutic potential for the treatment of rheumatoid arthritis [171] .
Skin disorders
Eculizumab completed a phase Ib pilot trial in patients with severe psoriasis. Based on preliminary analysis of data from this study, Alexion stated that it may consider further trials of the antibody in patients with psoriasis or psoriatic arthritis. Eculizumab was also in phase Ib trials for bullous pemphigoid. However, Alexion discontinued development in this indication to focus its resources on development for paroxysmal nocturnal haemoglobinuria.
A phase I, pilot trial was completed in patients with dermatomyositis, an inflammatory skin and muscle disorder, for which eculizumab has orphan drug status in the US.
Systemic lupus erythematosus
Eculizumab was undergoing phase II trials in the US in patients with systemic lupus erythematosus. However, Alexion discontinued development in this indication to focus its resources on development for paroxysmal nocturnal haemoglobinuria.
Other investigator sponsored trials
NHS Greater Glasgow and Clyde in collaboration with the University of Glasgow initiated a phase II trial to assess the inhibition of complement activation in Guillain-Barre Syndrome (GN12NE462; NCT02029378; EudraCT2013-000228-33). Primary endpoints were incidence of adverse and serious adverse events and improvement of one or more grade in functional outcome at four weeks. The randomised, double-blind trial was designed to enrol 30 patients in the UK. However, the trial was prematurely ended [172] .
Other indications
Eculizumab was being investigated in preclinical studies for the treatment of adult respiratory distress syndrome and immune (idiopathic) thrombocytopenic purpura. However, Alexion discontinued development in these indications to focus its resources on development for paroxysmal nocturnal haemoglobinuria.
Labelling information
In April 2015, the EMA approved the labelling changes made to the EU labels of eculizumab to include information related to the use of drug in patients with paroxysmal nocturnal haemoglobinuria (PNH) regardless of history of transfusion. Additionally, the label was also amended to to include new atypical haemolytic uraemic syndrome (aHUS) long-term efficacy data and the risks associated with the discontinuation of treatment [173] .
In May 2014, revised label information for the use of eculizumab in the treatment of aHUS in adults and paediatrics was approved. The label changes specify the benefits of chronic and sustained treatment with eculizumab and includes data from two years of treatment, and data on the use of eculizumab prior to supportive care with plasma exchange or plasma [18] .
The US product label for eculizumab includes a boxed warning stating that eculizumab increases the risk of meningococcal infections. During clinical studies, two out of 196 vaccinated patients with PNH treated with eculizumab experienced a serious meningococcal infection. Its is advised that patients should receive a meningococcal vaccine at least 2 weeks prior to receiving the first dose of eculizumab and then re-vaccinate according to current medical guidelines for vaccine use [123] . A similar boxed warning appears on the EU label [24] .
Patent Information
In November 2017, Alexion Pharmaceuticals announced that the Japanese Patent Office issued patent No. 6 224 059, related to the composition of matter of eculizumab (Soliris®) and pharmaceutical formulations of eculizumab, which will expire in 2027 [174] .
The US Patent and Trademark Office, in August 2017, issued US Patent Nos. 9 732 149, 9 718 880 and 9 725 504, related to composition of matter, pharmaceutical formulations, and methods of treating paroxysmal nocturnal haemoglobinuria (PNH) with eculizumab, respectively. The composition of matter patent covers the full-length amino acid sequence of eculizumab as well as other molecules with the same sequence, while the formulation patent provides for eculizumab containing pharmaceutical compositions, regardless of the intended use. The method of use patent also supplements other patents that cover treatment of atypical haemolytic uraemic syndrome and other complement-mediated diseases with eculizumab. All three patents are due to expire in 2027. Corresponding patent applications are being pursued in other regions, including Europe and Japan, in addition to applications for pending additional indications such as refractory generalized myasthenia gravis [175] .
Eculizumab is covered by US Patent No. 6 355 245, which extends to C5-specific monoclonal antibodies for the treatment of inflammatory diseases. Alexion reported in its Form 10-K (filed 17 February 2012) that an issued US patent covering eculizumab will expire in 2021. A corresponding European patent expires in 2015, with certain countries extending exclusivity until 2020 where a Supplementary Certificates of Protection has been granted. Patents covering eculizumab in Japan and other countries expire between 2015 and 2020.
The Japanese Patent Office issued patent No. 3 734 266 for eculizumab in Japan, in February 2006. The patent includes the use of eculizumab to inhibit complement activation in humans, the key mechanism of action used for the treatment of paroxysmal nocturnal haemoglobinuria. Corresponding patents have been issued or are pending in Europe, Canada, Australia and other key markets [176] .
Patent disputes
In April 2018, Alexion Pharmaceuticals clarified about the recent media reports stating that the brazilian superior court of justice has granted a compulsory license of eculizumab. The company confirmed that no compulsory license of eculizumab was requested or granted in Brazil. Alexion further stated that the recent decision by the court refers to a different legal matter with the brazilian patent office related to a eculizumab mailbox patent that expired in 2015. The company will respond to the court in this patent case after evaluation the court's decision. Alexion continues to have patent applications pending in Brazil that would provide additional protection to the drug [177] .
Alexion reported in its Form 10-K (filed 17 February 2011) that in January 2011, Novartis filed a civil action in the US District Court for the District of Delaware alleging that the manufacture of eculizumab wilfully infringes their US patent no. 5 688 688. Novartis seeks, among other things, monetary damages.
In March 2007, PDL BioPharma filed a civil action against Alexion in the US, claiming wilful infringement by Alexion of PDL's Queen et al patents (no. 5 693 761, 5 693 762, and 6 180 370 B1) related to eculizumab. In January 2008, the two companies entered into a definitive licence and settlement agreement to resolve the dispute. Under the agreements, PDL has granted Alexion a licence under certain claims in the Queen patents, permitting Alexion to commercialise eculizumab for all indications under the Queen patents. In exchange, Alexion will pay PDL $US25 million. PDL has separately granted Alexion the right to take a royalty-bearing licence to commercialise additional Alexion humanized antibodies that may be covered by the Queen patents in the future [178] .
In March 2007, Oklahoma Medical Research Foundation (OMRF) filed a civil action against Alexion in the US, alleging, among other things, wilful infringement by Alexion of certain OMRF patents related to complement-inhibition technology. During the first quarter of 2008, Alexion agreed to acquire all rights to the relevant patents for a total payment of $US10 million.
In January 2008, SB2 Inc filed a civil action against Alexion in the US, claiming wilful infringement by Alexion of SB2 patents due to sales of eculizumab. SB2 seeks unspecified monetary damages, equitable relief and attorney's fees. Alexion believed it has good and valid defences to SB2's claims and intended to vigorously defend the case.
Drug Properties & Chemical Synopsis
- Route of administration Inhalation, Intravitreous, IV, Parenteral
- Formulation Aerosol, Infusion, unspecified
- Class Anti-inflammatories, Antiallergics, Antianaemics, Antiasthmatics, Antihypertensives, Antipsoriatics, Antirheumatics, Eye disorder therapies, Monoclonal antibodies, Neuroprotectants, Skin disorder therapies, Urologics
- Target Complement C5
- Mechanism of Action Complement C5 inhibitors
-
WHO ATC code
B03 (Antianemic Preparations)
B06 (Other Hematological Agents)
D05 (Antipsoriatics)
G02C-X (Other gynecologicals)
G04 (Urologicals)
J05 (Antivirals for Systemic Use)
L04A-A25 (Eculizumab)
M01 (Antiinflammatory and Antirheumatic Products)
M09A (Other Drugs for Disorders of the Musculo-Skeletal System)
N07X (Other Nervous System Drugs)
R03 (Drugs for Obstructive Airway Diseases)
R07A (Other Respiratory System Products)
S01X (Other Ophthalmologicals)
-
EPhMRA code
B3 (Anti-Anaemic Preparations)
B6 (All Other Haematological Agents)
D5 (Nonsteroidal Products for Inflammatory Skin Disorders)
G2X9 (Other gynaecologicals)
G4 (Urologicals)
J5 (Antivirals for Systemic Use)
L4X (Other Immunosuppressants)
M1 (Anti-Inflammatory and Anti-Rheumatic Products)
M1A (Anti-Rheumatics, Non-Steroidal)
M5X (All Other Musculoskeletal Products)
N7X (All other CNS drugs)
R3 (Anti-Asthma and COPD Products)
R7 (Other Respiratory System Products)
S1X (Other Ophthalmologicals)
- Chemical name Immunoglobulin, anti-(human complement C5 a-chain) (human-mouse monoclonal 5G1.1 heavy chain), disulfide with human-mouse monoclonal 5G.1.1 light chain, dimer
- CAS Registry Number 219685-50-4
Biomarkers Sourced From Trials
| Indication | Biomarker Function | Biomarker Name | Number of Trials |
|---|---|---|---|
|
Atypical Haemolytic Uraemic Syndrome |
Eligibility Criteria |
ZFP36 ring finger protein Thymidine 5'-triphosphate SH3 domain binding protein 4 CD46 molecule, complement regulatory protein CAPG ADAMTS13 |
|
|
Atypical Haemolytic Uraemic Syndrome |
Outcome Measure |
Lactate dehydrogenase (LDH) |
|
|
autoimmune haemolytic anaemia |
Outcome Measure |
Lactate dehydrogenase (LDH) Hemopexin Haptoglobin |
|
|
delayed graft function |
Eligibility Criteria |
S100 calcium binding protein A6 5-Phosphoribosylamine |
|
|
graft-versus-host disease |
Brief Summary |
C5 |
|
|
graft-versus-host disease |
Detailed Description |
Tumor necrosis factor alpha (TNF-alpha) mannan-binding lectin serine peptidase 2 mannan-binding lectin serine peptidase 1 (C4/C2 activating component of Ra-reactive factor) Interferon Gamma (IFNg) Hematopoietic progenitor cell antigen CD34 Fc fragment of IgG receptor Ib C5 ADAMTS13 |
|
|
Guillain-Barre syndrome |
Outcome Measure |
cystatin F |
|
|
haemolysis |
Detailed Description |
Haptoglobin |
|
|
haemolysis |
Outcome Measure |
Haptoglobin |
|
|
Haemolytic uraemic syndrome |
Eligibility Criteria |
midnolin |
|
|
Haemolytic uraemic syndrome |
Outcome Measure |
CD46 molecule, complement regulatory protein |
|
|
heart transplant rejection |
Eligibility Criteria |
S100 calcium binding protein A6 Cytokeratin 20 B-lymphocyte antigen CD20 5-Phosphoribosylamine |
|
|
immune haemolysis |
Arm Group Label |
SERPINA2 CD55 molecule (Cromer blood group) |
|
|
immune haemolysis |
Brief Title |
CD55 molecule (Cromer blood group) |
|
|
immune haemolysis |
Arm Group Description |
SERPINA2 CD55 molecule (Cromer blood group) |
|
|
immune haemolysis |
Detailed Description |
SERPINA2 CFB CD55 molecule (Cromer blood group) C5 C3 |
|
|
immune haemolysis |
Official Title |
CD55 molecule (Cromer blood group) |
|
|
immune haemolysis |
Brief Summary |
SERPINA2 CD55 molecule (Cromer blood group) |
|
|
Inborn genetic disorders |
Arm Group Label |
SERPINA2 CD55 molecule (Cromer blood group) |
|
|
Inborn genetic disorders |
Brief Title |
CD55 molecule (Cromer blood group) |
|
|
Inborn genetic disorders |
Arm Group Description |
SERPINA2 CD55 molecule (Cromer blood group) |
|
|
Inborn genetic disorders |
Detailed Description |
SERPINA2 CFB CD55 molecule (Cromer blood group) C5 C3 |
|
|
Inborn genetic disorders |
Official Title |
CD55 molecule (Cromer blood group) |
|
|
Inborn genetic disorders |
Brief Summary |
SERPINA2 CD55 molecule (Cromer blood group) |
|
|
liver injury |
Outcome Measure |
LOC102724197 gamma-glutamyltransferase light chain 1 |
|
|
membranoproliferative glomerulonephritis |
Eligibility Criteria |
Creatinine |
|
|
multiple organ failure |
Eligibility Criteria |
ZFP36 ring finger protein Thymidine 5'-triphosphate SH3 domain binding protein 4 |
|
|
myasthenia gravis |
Brief Title |
C5 |
|
|
myasthenia gravis |
Eligibility Criteria |
Acetylcholine receptor |
|
|
myasthenia gravis |
Official Title |
C5 |
|
|
myasthenia gravis |
Outcome Measure |
S100 calcium binding protein A9 S100 calcium binding protein A8 |
|
|
neuromyelitis optica |
Brief Summary |
NMO Autoantibodies Aquaporin 4 Auto-antibodies Aquaporin 4 |
|
|
neuromyelitis optica |
Brief Title |
NMO Autoantibodies Aquaporin 4 Auto-antibodies Aquaporin 4 |
|
|
neuromyelitis optica |
Eligibility Criteria |
NMO Autoantibodies Aquaporin 4 Auto-antibodies Aquaporin 4 |
|
|
paroxysmal nocturnal haemoglobinuria |
Detailed Description |
C5 |
|
|
paroxysmal nocturnal haemoglobinuria |
Eligibility Criteria |
Lactate dehydrogenase (LDH) Glycosylphosphatidylinositols C-reactive protein (CRP) |
|
|
paroxysmal nocturnal haemoglobinuria |
Outcome Measure |
Haptoglobin Bilirubin |
|
|
preeclampsia |
Eligibility Criteria |
Fibrinogen |
|
|
preeclampsia |
Outcome Measure |
VEGFR1 PLGF CD59 molecule, complement regulatory protein C5 |
|
|
pregnancy complications |
Detailed Description |
Adenomatous polyposis coli protein (APC) |
|
|
renal transplant rejection |
Brief Summary |
G protein-coupled receptor 182 |
|
|
renal transplant rejection |
Detailed Description |
G protein-coupled receptor 182 |
|
|
renal transplant rejection |
Outcome Measure |
tissue factor pathway inhibitor (lipoprotein-associated coagulation inhibitor) G protein-coupled receptor 182 Creatinine |
|
|
thrombotic microangiopathy |
Arm Group Label |
SERPINA2 CD55 molecule (Cromer blood group) |
|
|
thrombotic microangiopathy |
Brief Title |
CD55 molecule (Cromer blood group) |
|
|
thrombotic microangiopathy |
Arm Group Description |
SERPINA2 CD55 molecule (Cromer blood group) |
|
|
thrombotic microangiopathy |
Detailed Description |
Tumor necrosis factor alpha (TNF-alpha) SERPINA2 mannan-binding lectin serine peptidase 2 mannan-binding lectin serine peptidase 1 (C4/C2 activating component of Ra-reactive factor) Interferon Gamma (IFNg) Hematopoietic progenitor cell antigen CD34 Fc fragment of IgG receptor Ib CFB CD55 molecule (Cromer blood group) C5 C3 ADAMTS13 |
|
|
thrombotic microangiopathy |
Eligibility Criteria |
ZFP36 ring finger protein Thymidine 5'-triphosphate SH3 domain binding protein 4 |
|
|
thrombotic microangiopathy |
Official Title |
CD55 molecule (Cromer blood group) |
|
|
thrombotic microangiopathy |
Brief Summary |
SERPINA2 CD55 molecule (Cromer blood group) C5 |
|
|
transplant rejection |
Eligibility Criteria |
C-peptide |
|
|
transplant rejection |
Outcome Measure |
Cystatin C C-peptide |
Biomarker
| Drug Name | Biomarker Name | Biomarker Function |
|---|---|---|
| Eculizumab - Alexion AstraZencea Rare Disease | 5-Phosphoribosylamine | Eligibility Criteria |
| Acetylcholine receptor | Eligibility Criteria | |
| ADAMTS13 | Detailed Description, Eligibility Criteria | |
| Adenomatous polyposis coli protein (APC) | Detailed Description | |
| Aquaporin 4 | Brief Summary, Brief Title, Eligibility Criteria | |
| Aquaporin 4 Auto-antibodies | Brief Summary, Brief Title, Eligibility Criteria | |
| B-lymphocyte antigen CD20 | Arm Group Description, Eligibility Criteria | |
| Bilirubin | Outcome Measure | |
| C-peptide | Eligibility Criteria, Outcome Measure | |
| C-reactive protein (CRP) | Eligibility Criteria | |
| C3 | Detailed Description, Outcome Measure | |
| C5 | Arm Group Description, Arm Group Label, Brief Summary, Brief Title, Detailed Description, Eligibility Criteria, Official Title, Outcome Measure | |
| CAPG | Eligibility Criteria | |
| CD46 molecule, complement regulatory protein | Eligibility Criteria, Outcome Measure | |
| CD55 molecule (Cromer blood group) | Arm Group Description, Arm Group Label, Brief Summary, Brief Title, Detailed Description, Official Title | |
| CD59 molecule, complement regulatory protein | Outcome Measure | |
| CFB | Detailed Description | |
| CFH | Eligibility Criteria | |
| Creatinine | Brief Summary, Eligibility Criteria, Outcome Measure | |
| Cystatin C | Outcome Measure | |
| cystatin F | Outcome Measure | |
| Cytokeratin 20 | Arm Group Description, Eligibility Criteria | |
| Cytokeratin 5 | Brief Summary, Eligibility Criteria | |
| Erythropoietin (EPO) | Eligibility Criteria | |
| Fc fragment of IgG receptor Ib | Detailed Description | |
| Fibrinogen | Eligibility Criteria | |
| G protein-coupled receptor 182 | Brief Summary, Detailed Description, Outcome Measure | |
| gamma-glutamyltransferase light chain 1 | Outcome Measure | |
| Glycosylphosphatidylinositols | Eligibility Criteria | |
| GPI | Eligibility Criteria | |
| Haptoglobin | Detailed Description, Outcome Measure | |
| Hematopoietic progenitor cell antigen CD34 | Detailed Description | |
| Hemopexin | Outcome Measure | |
| Interferon Gamma (IFNg) | Detailed Description | |
| Lactate dehydrogenase (LDH) | Eligibility Criteria, Outcome Measure | |
| LOC102724197 | Outcome Measure | |
| mannan-binding lectin serine peptidase 1 (C4/C2 activating component of Ra-reactive factor) | Detailed Description | |
| mannan-binding lectin serine peptidase 2 | Detailed Description | |
| midnolin | Eligibility Criteria | |
| NMO Autoantibodies | Brief Summary, Brief Title, Eligibility Criteria | |
| optineurin | Eligibility Criteria | |
| PLGF | Outcome Measure | |
| S100 calcium binding protein A6 | Eligibility Criteria | |
| S100 calcium binding protein A8 | Outcome Measure | |
| S100 calcium binding protein A9 | Outcome Measure | |
| SERPINA2 | Arm Group Description, Arm Group Label, Brief Summary, Detailed Description | |
| SH3 domain binding protein 4 | Eligibility Criteria | |
| Thymidine 5'-triphosphate | Eligibility Criteria | |
| tissue factor pathway inhibitor (lipoprotein-associated coagulation inhibitor) | Outcome Measure | |
| Tumor necrosis factor alpha (TNF-alpha) | Detailed Description | |
| VEGFR1 | Outcome Measure | |
| ZFP36 ring finger protein | Eligibility Criteria |
Development Status
Summary Table
| Indication | Qualifier | Patient Segment | Phase | Countries | Route / Formulation | Developers | Event Date |
|---|---|---|---|---|---|---|---|
| Adult respiratory distress syndrome | - | - | Discontinued (Preclinical) | USA | Parenteral / unspecified | Alexion Pharmaceuticals | 21 Nov 2006 |
| Age-related macular degeneration | - | - | Discontinued (II) | USA | Intravitreous / unspecified | Alexion Pharmaceuticals | 06 Feb 2015 |
| Age-related macular degeneration | - | - | Discontinued (II) | USA | IV / Infusion | Alexion Pharmaceuticals | 06 Feb 2015 |
| Allergic asthma | - | - | Discontinued (II) | Canada | IV / Infusion | Alexion Pharmaceuticals | 23 Feb 2010 |
| Allergic asthma | - | - | Discontinued (Preclinical) | USA | Inhalation / Aerosol | Alexion Pharmaceuticals | 23 Feb 2010 |
| Antiphospholipid syndrome | Catastrophic antiphospholipid syndrome (CAPS) | - | No development reported (II) | USA | Parenteral / unspecified | Alexion Pharmaceuticals | 25 Jun 2013 |
| Autoimmune haemolytic anaemia | Cold agglutinin disease | - | Discontinued (II) | USA | Parenteral / unspecified | Alexion Pharmaceuticals | 06 Feb 2015 |
| Bullous pemphigoid | - | - | Discontinued (I) | USA | Parenteral / unspecified | Alexion Pharmaceuticals | 26 Sep 2005 |
| COVID-19 pneumonia | emergency expanded access programme | - | No development reported (Clinical) | France, USA | IV / unspecified | Alexion AstraZeneca Rare Disease | 28 Mar 2024 |
| Delayed graft function | - | Prevention | Phase III | Australia, Canada, Czech Republic, Germany, Italy, Spain, USA | IV / Infusion | Alexion AstraZeneca Rare Disease | 06 Feb 2015 |
| Delayed graft function | - | Prevention | Phase II/III | France | IV / Infusion | Alexion AstraZeneca Rare Disease | 01 Jul 2014 |
| Dermatomyositis | - | - | Discontinued (I) | USA | Parenteral / unspecified | Alexion Pharmaceuticals | 26 Sep 2005 |
| Glomerulonephritis | Type II membranoproliferative glomerulonephritis (dense deposit disease) | - | Discontinued (II) | USA | Parenteral / unspecified | Alexion Pharmaceuticals | 06 Feb 2015 |
| Guillain-Barre syndrome | - | Adjunctive treatment | Phase III | Japan | IV / Infusion | Alexion AstraZeneca Rare Disease | 01 Feb 2021 |
| Haemolytic uraemic syndrome | Atypical haemolytic uraemic syndrome (aHUS) | In adolescents, In adults, In children | Marketed | Japan | IV / Infusion | Alexion AstraZeneca Rare Disease | 29 Apr 2014 |
| Haemolytic uraemic syndrome | Atypical haemolytic uraemic syndrome (aHUS) Atypical haemolytic uraemic syndrome (aHUS); centralised procedure | In adolescents, In adults, In children, In infants | Marketed | Canada, Czech Republic, European Union, Israel, Netherlands, Spain, USA, United Kingdom | IV / Infusion | Alexion AstraZeneca Rare Disease | 14 Aug 2014 |
| Haemolytic uraemic syndrome | Atypical Hemolytic Uremic Syndrome (aHUS) | In adolescents, In adults, In children, In infants | Marketed | South Korea | IV / Infusion | Handok Inc | 01 Jan 2012 |
| Haemolytic uraemic syndrome | patients with atypical hemolytic uremic syndrome (aHUS) who are complement inhibitor treatment-naïve | In adolescents, In adults, In children, In the elderly | Registered | China | IV / Infusion | Alexion AstraZeneca Rare Disease | 24 Aug 2023 |
| Heart transplant rejection | - | Prevention | No development reported (Preclinical) | USA | Parenteral / unspecified | Alexion AstraZeneca Rare Disease | 04 Nov 2017 |
| Idiopathic thrombocytopenic purpura | - | - | Discontinued (Preclinical) | USA | Parenteral / unspecified | Alexion Pharmaceuticals | 21 Nov 2006 |
| Lupus nephritis | - | - | Discontinued (II) | USA | Parenteral / unspecified | Alexion Pharmaceuticals | 26 Sep 2005 |
| Membranous glomerulonephritis | - | - | Discontinued (II) | USA | Parenteral / unspecified | Alexion Pharmaceuticals | 26 Sep 2005 |
| Motor neuron disease | Multifocal motor neuropathy | - | Discontinued (II) | USA | IV / unspecified | Alexion Pharmaceuticals | 06 Feb 2015 |
| Myasthenia gravis | - | In adolescents, In children, Treatment-experienced | Marketed | Japan | IV / Infusion | Alexion AstraZeneca Rare Disease | 24 Aug 2023 |
| Myasthenia gravis | Refractory generalised myasthenia gravis in adults who are anti-acetylcholine receptor antibody-positive | In adults, Treatment-experienced | Marketed | Germany | IV / Infusion | Alexion AstraZeneca Rare Disease | 31 Dec 2017 |
| Myasthenia gravis | patients with gMG who AChR antibody-positive and whose symptoms are difficult to control with high-dose intravenous immunoglobulin (IVIG) therapy or plasmapheresis | Treatment-experienced | Marketed | Japan, USA | IV / Infusion | Alexion AstraZeneca Rare Disease | 31 Dec 2017 |
| Myasthenia gravis | Refractory generalised myasthenia gravis in adults who are anti-acetylcholine receptor antibody-positive | In adults, Treatment-experienced | Registered | European Union, Iceland, Liechtenstein, Norway | IV / Infusion | Alexion AstraZeneca Rare Disease | 21 Aug 2017 |
| Myasthenia gravis | in children and adolescents aged six to 17 | In adolescents, In children, Treatment-experienced | Registered | European Union, Iceland, Liechtenstein, Norway | IV / Infusion | Alexion AstraZeneca Rare Disease | 27 Jul 2023 |
| Myasthenia gravis | - | - | Registered | China | IV / Infusion | Alexion AstraZeneca Rare Disease | 13 Jun 2023 |
| Myasthenia gravis | - | In adolescents, In children, Treatment-experienced | Phase III | USA | IV / Infusion | Alexion AstraZeneca Rare Disease | 21 Dec 2018 |
| Myasthenia gravis | - | - | Phase III | Australia, Brazil, Canada, South Korea, Turkey | IV / Infusion | Alexion AstraZeneca Rare Disease | 01 Dec 2013 |
| Neuromyelitis optica | - | - | Marketed | Czech Republic, Netherlands, Spain, USA, United Kingdom | IV / Infusion | Alexion AstraZeneca Rare Disease | 29 Aug 2019 |
| Neuromyelitis optica | - | In adults, In the elderly | Marketed | Japan | IV / Infusion | Alexion AstraZeneca Rare Disease | 23 Nov 2019 |
| Neuromyelitis optica | - | - | Registered | European Union, Iceland, Liechtenstein, Norway | IV / Infusion | Alexion AstraZeneca Rare Disease | 29 Aug 2019 |
| Neuromyelitis optica | - | In adults | Registered | China | IV / Infusion | Alexion AstraZeneca Rare Disease | 18 Oct 2023 |
| Neuromyelitis optica | - | - | Phase III | Argentina, Australia, Austria, Canada, Colombia, Croatia, France, Hong Kong, Malaysia, Russia, Singapore, South Korea, Taiwan, Thailand, Turkey | IV / Infusion | Alexion AstraZeneca Rare Disease | 31 Jan 2015 |
| Neuromyelitis optica | 2 Years to 17 Years | In adolescents, In children | Phase II/III | Canada, Germany, Italy, Japan, Spain, USA | IV / Infusion | Alexion AstraZeneca Rare Disease | 14 Jan 2020 |
| Paroxysmal nocturnal haemoglobinuria | - | - | Marketed | Argentina, Australia, Canada, Finland, Israel, Japan, Luxembourg, Mexico, Russia, Switzerland, Taiwan, USA, United Kingdom | IV / Infusion | Alexion AstraZeneca Rare Disease | 11 Nov 2014 |
| Paroxysmal nocturnal haemoglobinuria | - | - | Marketed | South Korea | IV / Infusion | Handok Inc | 01 Jan 2012 |
| Paroxysmal nocturnal haemoglobinuria | - | In adolescents, In adults, In children | Marketed | Austria, Belgium, Czech Republic, Denmark, France, Germany, Ireland, Italy, Netherlands, New Zealand, Norway, Poland, Portugal, Spain, Sweden | IV / Infusion | Alexion AstraZeneca Rare Disease | 11 Nov 2014 |
| Paroxysmal nocturnal haemoglobinuria | - | Treatment-naive | Registered | China | IV / Infusion | Alexion AstraZeneca Rare Disease | 24 Aug 2023 |
| Paroxysmal nocturnal haemoglobinuria | - | In adolescents, In children | Phase I/II | USA | IV / Infusion | Alexion AstraZeneca Rare Disease | 01 May 2009 |
| Preeclampsia | women with preeclampsia between 23-30 weeks gestation | In adolescents, In adults, In the elderly | Phase II | USA | IV / unspecified | Alexion AstraZeneca Rare Disease | 13 Sep 2021 |
| Psoriasis | - | - | Discontinued (I) | USA | Parenteral / unspecified | Alexion Pharmaceuticals | 26 Sep 2005 |
| Renal transplant rejection | - | Prevention | Phase II | Australia, France, Germany, Italy, Netherlands, Norway, Spain, Sweden, USA, United Kingdom | IV / Infusion | Alexion AstraZeneca Rare Disease | 25 Jul 2013 |
| Renal transplant rejection | - | - | Phase II | USA | IV / Infusion | Alexion AstraZeneca Rare Disease, Brigham and Womens Hospital | 30 Nov 2013 |
| Rheumatoid arthritis | - | - | Discontinued (II/III) | Canada, USA | IV / Infusion | Alexion Pharmaceuticals | 26 Sep 2005 |
| SARS-CoV-2 acute respiratory disease | emergency expanded access programme | - | No development reported (Clinical) | France, USA | IV / unspecified | Alexion AstraZeneca Rare Disease | 28 Mar 2024 |
| Systemic lupus erythematosus | - | - | Discontinued (II) | USA | Parenteral / unspecified | Alexion Pharmaceuticals | 26 Sep 2005 |
Orphan Status
| Indication | Patient Segment | Country | Organisation | Event Date |
|---|---|---|---|---|
| Delayed graft function | Prevention | European Union | Alexion AstraZeneca Rare Disease | 24 Feb 2014 |
| Delayed graft function | Prevention | USA | Alexion AstraZeneca Rare Disease | 21 Jan 2014 |
| Dermatomyositis | - | USA | Alexion AstraZeneca Rare Disease | 06 Oct 2000 |
| Haemolytic uraemic syndrome | - | USA | Alexion AstraZeneca Rare Disease | 31 Dec 2009 |
| Haemolytic uraemic syndrome | - | European Union | Alexion AstraZeneca Rare Disease | 07 Aug 2009 |
| Membranous glomerulonephritis | - | USA | Alexion AstraZeneca Rare Disease | 05 Mar 2001 |
| Myasthenia gravis | - | European Union | Alexion AstraZeneca Rare Disease | 01 Aug 2014 |
| Myasthenia gravis | - | Japan | Alexion AstraZeneca Rare Disease | 10 Dec 2014 |
| Myasthenia gravis | - | USA | Alexion AstraZeneca Rare Disease | 17 Jun 2014 |
| Neuromyelitis optica | - | USA | Alexion AstraZeneca Rare Disease | 27 Jun 2013 |
| Neuromyelitis optica | - | Japan | Alexion AstraZeneca Rare Disease | 25 Nov 2014 |
| Neuromyelitis optica | - | European Union | Alexion AstraZeneca Rare Disease | 31 Aug 2013 |
| Paroxysmal nocturnal haemoglobinuria | - | USA | Alexion AstraZeneca Rare Disease | 08 Dec 2003 |
| Paroxysmal nocturnal haemoglobinuria | - | South Korea | Alexion AstraZeneca Rare Disease | 25 Feb 2011 |
| Paroxysmal nocturnal haemoglobinuria | - | Canada | Alexion AstraZeneca Rare Disease | 26 Feb 2009 |
| Paroxysmal nocturnal haemoglobinuria | - | European Union | Alexion AstraZeneca Rare Disease | 08 Dec 2003 |
| Paroxysmal nocturnal haemoglobinuria | - | Australia | Alexion AstraZeneca Rare Disease | 10 Apr 2007 |
| Paroxysmal nocturnal haemoglobinuria | - | Japan | Alexion AstraZeneca Rare Disease | 13 Jan 2009 |
| Transplant rejection | Prevention | European Union | Alexion AstraZeneca Rare Disease | 23 Apr 2014 |
Commercial Information
Involved Organisations
| Organisation | Involvement | Countries |
|---|---|---|
| Alexion Pharmaceuticals | Originator | USA |
| Alexion AstraZeneca Rare Disease | Owner | USA |
| Handok Inc | Market Licensee | South Korea |
| Icahn School of Medicine at Mount Sinai | Collaborator | USA |
| Chiba University | Collaborator | Japan |
| Mayo Clinic | Collaborator | USA |
| Brigham and Womens Hospital | Collaborator | USA |
Brand Names
| Brand Name | Organisations | Indications | Countries |
|---|---|---|---|
| Soliris | Alexion AstraZeneca Rare Disease | Haemolytic uraemic syndrome, Paroxysmal nocturnal haemoglobinuria, Myasthenia gravis, Neuromyelitis optica | European Union, Japan, USA |
Credit Suisse Market Status
| Indication | Region | Company | Phase | Expected Launch Year | Probability of Success% | Patent Expiry Year | Expected Generic Entry | Last Update |
|---|---|---|---|---|---|---|---|---|
| Myasthenia gravis | ex US | AstraZeneca | Marketed | 2017 | 100 | 2027 | 01 Jun 2027 | 05 Nov 2023 |
| Myasthenia gravis | US | AstraZeneca | Marketed | 2017 | 100 | 2025 | 01 Mar 2025 | 05 Nov 2023 |
| Neuromyelitis Optica | ex US | AstraZeneca | Marketed | 2019 | 100 | 2025 | 01 Mar 2025 | 05 Nov 2023 |
| Neuromyelitis Optica | US | AstraZeneca | Marketed | 2019 | 100 | 2025 | 01 Mar 2025 | 05 Nov 2023 |
| PNH/aHUS | ex US | AstraZeneca | Marketed | 2009 | 100 | 2023 | 01 Sep 2023 | 05 Nov 2023 |
| PNH/aHUS | US | AstraZeneca | Marketed | 2007 | 100 | 2025 | 01 Mar 2025 | 05 Nov 2023 |
Credit Suisse Financial Forecast
| Indication | Region | 2021 | 2022 | 2023 | 2024 | 2025 | 2026 | 2027 | 2028 | 2029 | 2030 | Last Update |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Myasthenia gravis | ex US | 295 | 250 | 200 | 200 | 100 | 50 | 50 | 50 | 50 | 49 | 05 Nov 2023 |
| Myasthenia gravis | US | 467 | 980 | 800 | 350 | 225 | 100 | 100 | 100 | 99 | 98 | 05 Nov 2023 |
| Neuromyelitis Optica | ex US | 45 | 32 | 82 | 150 | 100 | 50 | 50 | 50 | 40 | 40 | 05 Nov 2023 |
| Neuromyelitis Optica | US | 251 | 600 | 420 | 290 | 100 | 100 | 100 | 100 | 99 | 98 | 05 Nov 2023 |
| PNH/aHUS | ex US | 1410 | 1300 | 1000 | 800 | 500 | 200 | 200 | 200 | 198 | 196 | 05 Nov 2023 |
| PNH/aHUS | US | 351 | 650 | 500 | 400 | 300 | 100 | 100 | 100 | 99 | 98 | 05 Nov 2023 |
| Total | 2819 | 3812 | 3002 | 2190 | 1325 | 600 | 600 | 600 | 585 | 579 |
Scientific Summary
-
Adverse Events
Occasional:
Anaemia; Back pain; Cough; Diarrhoea; Fever; Headache; Hypertension; Joint disorders; Muscle pain; Nasopharyngitis; Nausea; Oedema; Pain; Respiratory tract infections
Rare: Meningococcal infections
Adverse Events
Atypical haemolytic uraemic syndrome (aHUS)
Final data from two pivotal phase II studies have both demonstrated that eculizumab was well tolerated in patients with atypical haemolytic uraemic syndrome (aHUS). The most common serious adverse events (AEs) were accelerated hypertension, hypertension and influenza [44] . The most frequently reported AEs were headache, anaemia and diarrhoea (generally mild to moderate in severity). In the first study involving 17 adolescents and adults with aHUS who were resistant or intolerant to plasma exchange/infusion, 15 patients received eculizumab for 26 weeks and 2 patients did not complete the study but were included in the analysis. An extension trial continues. The second pivotal study enrolled patients with aHUS who were receiving chronic plasma exchange/infusion. The most frequently reported AEs were headache, diarrhoea, hypertension and nausea (generally mild to moderate in severity). In this 26-week study, 20 patients continued to receive plasma exchange/infusion during an 8-week observation period, and then discontinued plasma exchange/infusion and commenced eculizumab treatment. Patients in the second study received later intervention with eculizumab, compared with patients in the first study (median duration of aHUS from diagnosis to screening of 48 months vs 10 months, respectively) [26] . These final data were consistent with interim data reported in 2010 [45] . At two years, there was no increase in serious adverse events following ongoing treatment with eculizumab in patients enrolled in these phase II studies (C08-002A/B, C08-003A/B) [18] .
In a post-hoc analysis of 26 weeks, eculizumab, in the C10-004 phase II trial, was well tolerated with no unexpected safety signals in adult patients with or without identified genetic mutation. In the sub group of patients with an identified mutation, the most common adverse events were diarrhoea (47.6%), headache (38.1%), and peripheral oedema (33.3%), whereas headache (35.0%), pyrexia (25.0%), diarrhoea, hypotension, renal impairment urinary tract infection (20.0%) each were the most commonly reported adverse events in the sub group of patients without an identified mutation [47] . In the phase II trial, incidences of alopecia (7%), headache (37%), diarrhoea (32%), arthralgia (5%), asthenia (5%), peripheral oedema (22%) and pain in extremity were most frequently reported (C10-004). Two case of meningococcal infections were reported, one of these patients discontinued the treatment and later recovered, while the other continued treatment with no interruption and recovered without sequelae. In a subgroup analysis in patients with dialysis history, no unexpected adverse events were reported. Incidence of diarrhoea (29.2%), headache (33.3%) and hypotension (20.8%) were frequently reported by patients with baseline dialysis, while asthenia (29.4%), diarrhoea (35.3%) and headache (41.2) were commonly reported by those with no baseline dialysis. In another subgroup analysis, patients with renal transplant frequently reported haematoma (33.3%), anaemia (44.4%), diarrhoea (55.6%), renal impairment (33.3%) and urinary tract infection (33.3%). Incidence of cough (25%), diarrhoea (25%), headache (40.6%) and peripheral oedema (28.1%) were common in patients without renal transplant. A total of 41 adult patients with aHUS were enrolled in this open-label trial [48] [49] .
In a post-hoc analysis of 26 weeks, eculizumab, in the C10-003 phase II trials, was well tolerated with no unexpected safety signals in paediatric patients with or without identified genetic mutation. Meningococcal infections was not reported in the paediatric patients. In patients with an identified genetic mutation, in the C10-003 study, the most common adverse events were abdominal pain, pyrexia and upper respiratory tract infection (36.4%) each, whereas most common adverse events observed in patients without an identified mutation were pyrexia (63.3%), vomiting (63.6%), and cough (45.5%) [47] . Eculizumab was well tolerated in paediatric patients with aHUS in a prospective phase II trial (C10-003). Twenty-two patients aged >1 month and <18 years were enrolled, 19 of whom completed the planned 26-week treatment period. The most frequently reported adverse events were fever and cough, and one patient had an anti-human antibody response but was able to continue eculizumab therapy without apparent adverse effects [49] . No meningococcal infections or deaths were reported during the 26 week study. In a subgroup analysis in patients with dialysis history, no unexpected adverse events were reported. Incidence of diarrhoea (36.4%), pyrexia (45.5%), cough (36.4%), abdominal pain (36.4%) and nasopharyngitis (36.4%) were frequently reported by patients with no baseline dialysis, while cough (36.4%), respiratory tract infection (36.4%) and pyrexia (54.5%) were commonly reported by those with baseline dialysis [48] [18] .
Data from a retrospective clinical study of 15 paediatric patients (aged < 12 years) with aHUS, who received ≥ 1 dose of eculizumab outside of prospective clinical trials between 2007 and 2009, showed the most frequently reported AEs were fever, upper respiratory tract infection, diarrhoea and cough [26] .
Treatment with eculizumab was safe, well tolerated and was found to reduce the mortality risk by 89% at three years. The drug also showed an annual mortality rate of 1.4% in patients with aHUS. One death was reported, which was deemed unrelated to eculizumab. Predictive mortality rate, estimated using markov models, was 8.1% at one year, 16.2% at two years and 24.3% at three years. The survival analysis data was predicted in aHUS patients during a registrational trial [46] .
Eculizumab treatment was well-tolerated in 28 paediatric and adolescent patients with aHUS, according to a post-hoc analysis of safety data from three prospective clinical trials. No unexpected treatment-related adverse events (TRAEs) were noted and no deaths or meningococcal infections were reported. Most treatment-emergent adverse events (TEAEs) were mild to moderate in severity. Of the patients experiencing TEAEs, half (n=13) had events determined to be at least possibly related to The most common TRAEs reported after one year of treatment were skin/subcutaneous tissue disorders including alopecia, dermatitis, eczema, erythema and rash and infections/infestations. The infections included ear infection, fungal infection, nasopharyngitis and oral fungal infection. Four patients reported serious TRAEs by one year of treatment, including infections and agitation. By the end of the study (mean 67 weeks), 6 infection-related serious TRAEs occurred in four patients, including viral upper respiratory tract infection (n=2), influenza peritonitis, respiratory syncytial virus infection and pyelonephritis (n=1 each). None of the TRAEs led to treatment discontinuation, and all patients recovered [181] .
Delayed-graft function:
In the phase II/III PROTECT study, rates of serious adverse events, after the first 60 days of treatment, was observed as 54.1% and 44.4%, in the placebo group and eculizumab group, respectively. Four deaths were reported in the placebo group while only one death was reported in the eculizumab group, in the same time frame. Total 288 patients were treated in the study [162] [166] .
Dermatomyositis
In a phase I pilot trial, 13 patients with dermatomyositis were randomised to receive eculizumab or placebo. Eculizumab was administered intravenously at a dose of 8 mg/kg once a week for 5 weeks and then once every two weeks for up to two months. Adverse events were similar in drug-treated and placebo-treated groups. The most common adverse events were rash and headache [209] .
Membranous glomerulonephritis
In the double-blind, C99-004 trial, 117 patients with membranous nephritis were randomised to receive either placebo, eculizumab 8 mg/kg every four weeks, or eculizumab 8 mg/kg every two weeks for four months. Eculizumab appeared to be well tolerated, with the most common adverse events being upper respiratory tract infection, diarrhoea, and headache [203] .
In the E99-004 trial, 72 placebo and eculizumab patients with membranous nephritis from trial C99-004 were entered into a pre-planned, open-label extension study designed to provide eculizumab 8 mg/kg every two weeks for 12 months. The trial is still ongoing and current results show that eculizumab appears to be well tolerated with the most common adverse events being upper respiratory infections, nasal congestion/rhinitis, and headache [203] .
Myasthenia Gravis
Phase III
The most common adverse events in patients receiving eculizumab and placebo, respectively, from the phase III REGAIN study were: headache (16.1%, 19.0%), upper respiratory tract infection (16.1%, 19.0%), nasopharyngitis (14.5%, 15.9%), myasthenia gravis (9.7%, 17.5%), and nausea (12.9%, 14.3%). Serious adverse events were reported in 14.5% of eculizumab patients and 28.6% of placebo patients. Four patients receiving eculizumab (6.5%) discontinued treatment due to an adverse event. There were no discontinuations due to adverse events in the placebo arm [76] [81] .
Updated results from a phase III trial in paediatric and adolescent patients with refractory generalised myasthenia gravis (gMG) showed that the most common adverse events were headache and nasopharyngitis. Earlier results demonstrated that eculizumab was well-tolerated in adolescents with refractory generalised myasthenia gravis (gMG). Treatment-emergent adverse events were all mild/moderate and predominantly unrelated to eculizumab. Three patients experienced six serious adverse events (MG worsening, MG crisis, peritonsillar abscess, pyrexia). No meningococcal infections were reported [17] [73] [75] [74] .
Neuromyelitis optica
In the pivotal phase III PREVENT trial, in patients with anti-aquaporin-4 (AQP4) auto antibody-positive neuromyelitis optica, eculizumab was generally well tolerated with a safety profile consistent with that seen in previous clinical studies and real-world use in its three approved indications. Meningococcal infection cases were not observed in the trial. The most common adverse events observed were upper respiratory tract infection (29% of patients in the SOLIRIS group vs. 13% in the placebo group), headache (23 vs. 23%), nasopharyngitis (21 vs. 19%), nausea (17 vs. 26%), diarrhea (16 vs. 15%), back pain (15 vs. 13%) and dizziness (15 vs. 13%). The serious adverse events that were reported for more than one patient in either group were pneumonia (three patients in the eculizumab group vs. one patient in the placebo group) and cellulitis, sepsis and urinary tract infection (two patients for each event in the SOLIRIS group vs. no patient in the placebo group). One patient receiving SOLIRIS and concomitant supportive IST died from infectious pleural effusion. The patient had an extensive history of pulmonary disease and was an active smoker [214] [106] [103] [107] .
Pooled analysis
Updated long term data from phase III PREVENT and OLE trials showed that, eculizumab found to be safe and well tolerated. The treatment-related adverse event rate with eculizumab monotherapy was similar to that with placebo (181.0 versus 186.0 events/100 PY). The infection rate was similar between these groups (174.1 versus 186.0 events/100 PY), and the treatment-related serious adverse event rate was lower with eculizumab monotherapy than with placebo alone (5.7 versus 23.3 events/100 PY). No meningococcal infections or deaths occurred among these patients. In the phase III PREVENT and open-label extension (OLE) trial in 137 evaluable patients with neuromyelitis optica, eculizumab was well tolerated and the AEs reported were consistent with its established safety profile in other indications. The rates of AEs and serious AEs (SAEs) per 100 patient years were 763.1 and 37.6, respectively. Headache (27.0%), upper respiratory tract infection (25.5%), nasopharyngitis (22.6%), urinary tract infection (16.8%), nausea (16.1%), back pain (15.3%) and diarrhoea (15.3%) were adjudged as the most common AEs. Common SAEs, excluding NMOSD relapses, comprised pneumonia (2.9%), urinary tract infection (2.9%) and optic neuritis (2.2%). One death occurred during PREVENT trial owing to pulmonary empyema, while one patient developed Neisseria gonorrhoeae in the OLE. Meningococcal infection was not observed in any patient [100] [101] [107] [102] [111] .
In an open-label phase I/II trial eculizumab appeared to be well tolerated by patients with severe, relapsing neuromyelitis optica who received treatment for 12 months. The three most common adverse events were headache, nausea, and dizziness. One patient died of a myocardial infarction approximately 4 months after completing treatment with eculizumab; however, this event was deemed unrelated to eculizumab. During the first three months following the protocol-specified termination of eculizumab treatment, two patients, while continuing to receive immunosuppressive treatment, experienced three severe relapses. The study enrolled 14 women (median age: 41 years; range: 18-67 years) who received eculizumab 600mg once-weekly for the first 4 weeks, followed by eculizumab 900mg dose at week-5, and a 900mg maintenance dose q2w thereafter [113] .
Paroxysmal nocturnal haemoglobinuria (PNH)
In the US, the product carries a boxed warning that eculizumab increases the risk of meningococcal infections. Two out of 196 paroxysmal nocturnal haemoglobinuria (PNH) patients vaccinated with a meningococcal vaccine and treated with eculizumab experienced a serious meningococcal infection [198] .
Post-hoc analysis
a post-hoc analysis of data from controlled trials of eculizumab in patients with PNH who were receiving concomitant immunosuppressive therapy (IST) showed the similarity of the overall and infection-related adverse event rates and serious adverse event rates, to the overall clinical trial population. These adverse event rates did not increase over time. The analysis included a population of 195 patients, 17 of which were receiving IST. Patients were subdivided into groups comprising those who commenced eculizumab during ongoing IST and those who commenced IST during ongoing eculizumab treatment [189] .
Long-term data
in patients with PNH treated with eculizumab for up to 5.5 years, the incidence of patients reporting an AE in the last 26 weeks of treatment was significantly reduced compared with the incidence in the first 26 weeks (p < 0.001). The probability of a patient experiencing an AE decreased significantly with time (p<0.001). A low rate of meningococcal infection was observed with long-term treatment (0.422 per 100 patient-years). Two patients experienced meningococcal infections from strains not covered by their vaccinations. Both infections were successfully treated and both resolved without sequelae. Four patient deaths were reported over the course of the study and were not considered to be related to treatment [183] .
Phase III
eculizumab had an adverse event profile comparable to placebo in a trial of 87 patients with paroxysmal nocturnal haemoglobinuria (the TRIUMPH trial). The most frequent adverse events with eculizumab were headache, nasopharyngitis, and back pain [131] .
Eculizumab was well tolerated with an adverse event profile similar to that observed in the TRIUMPH trial in one-year results from the phase III open-label SHEPHERD trial. No serious adverse events were deemed probably or definitely related to eculizumab therapy. The most common adverse events reported with eculizumab treatment were headache, nasopharyngitis, nausea and upper respiratory tract infections. The events were generally consistent with those seen with six months of eculizumab and placebo treatment in the TRIUMPH trial. Interim results were previously reported [133] [135] .
Analysis of the phase III TRIUMPH and SHEPHERD trials, evaluating data from 39 patients who were diagnosed with PNH and who has a history of aplastic anaemia (AA) or myelodysplastic syndromes (MDS), showed that eculizumab was safe and well tolerated following 26 weeks of treatment [199] .
Phase II
eculizumab appeared to be safe and well tolerated during the initial 26-weeks extension of the AEGIS phase II study. Nine serious adverse events (AEs) occurred in four patients; one patient had four serious AEs that were considered probably or possibly related to eculizumab. Nasopharyngitis (52%), headache (19%), blood alkaline phosphatase increases (19%) and anaemia (11%) were the most frequent AEs. Most AEs were mild in severity. There were no thrombotic events or meningococcal infections reported during eculizumab treatment. The extension study enrolled 27 patients who received eculizumab 600mg every seven days (±2 days) for four weeks; 900mg one week later; then 900mg every 14 days (±2 days) [191] .
Eculizumab was safe and well tolerated in the open-label, phase II AEGIS trial which evaluated the drug in 29 patients with PNH in Japan. The most common adverse events were headache (52%), nasopharyngitis (41%) and nausea (21%). Adverse events were mostly mild to moderate in severity and were considered to be unrelated to eculizumab treatment. No serious drug-related adverse events were reported [193] .
Phase I
eculizumab was safe and well tolerated without any cases of antibodies against the drug detected among 11 patients with PNH in a phase Ib trial. The most common adverse events were headache, upper respiratory infection, sore throat, muscle/joint aches and influenza-like symptoms. Severe adverse events included viral chest infection, dizziness and shivering. Adverse events were similar in type and frequency to those reported with eculizumab or placebo in other controlled trials [142] [201] [202] . Two-year cumulative results from this study showed that eculizumab continued to be well tolerated. Four serious adverse events were reported but no patients discontinued treatment due to adverse events [143] .
Psoriasis
Treatment with eculizumab for two months was safe and generally well tolerated in a phase I pilot trial in 40 patients with psoriasis. Adverse events included headache and non-specific pain. 40% of placebo recipients and 10% of the treatment group withdrew from the study before completion [204] .
Renal transplant rejection
In an open-label, phase II trial in patients with antibody mediated rejection (AMR) following renal transplantation, at 1 year, the most common treatment-emergent serious adverse events were transplant rejection (28.8%), acute renal failure (12.5%) and complications of the transplanted kidney (15.0%). Overall, two deaths occurred, one due to multi-organ failure and one due to proximal small bowel perforation, which were not related to eculizumab [181] [149] .
No serious treatment-related adverse events, apart from transplant-related complications, were reported in a phase II trial of eculizumab in 47 recipients of deceased donor kidneys [153] .
Rheumatoid arthritis
Phase II
in a double-blind, randomised, placebo-controlled phase IIb trial in approximately 350 patients with chronic rheumatoid arthritis undergoing treatment with methotrexate or leflunomide, eculizumab was administered either once per month or biweekly for six months. The rates of both serious and common adverse events were similar for placebo and eculizumab. The most common adverse events were upper respiratory tract infections, headache and nausea. Serious adverse events included myocardial infarction, accidental injury and cerebral infarction [170] .
Phase I
in a multicentre, double-blind, placebo-controlled, ascending-dose, phase I/II trial, 40 patients with rheumatoid arthritis received a single dose of the antibody eculizumab. Within the dose range tested (0.1-8.0 mg/kg), eculizumab was safe and well-tolerated. It had no detectable immunogenicity [206] .
Pharmacodynamics
Summary
Atypical haemolytic uraemic syndrome (aHUS)
Phase II:
in a phase II trial, eculizumab significantly reduced inflammatory markers (sTNFR1) by up to 94%; after week 6, the reduction was sustained and significant across all later time points (p < 0.0001) (C10-004). Thrombomodulin, marker of endothelial damage, was also reduced to normal levels (p < 0.0001), which was significant across all later time points after week 17 (p < 0.0001). Eculizumab also significantly reduced coagulation markers (D-dimer) by up to 99%. The reduction remained marginally above the volunteer level at week 52 and was sustained for all time points (p < 0.0001). A reduction in markers of endothelial activation (sVCAM-1) and proximal complement (Ba) upstream of C5 was also observed in this trial. A total of 41 adult patients with aHUS were enrolled in this open-label trial [48] .
Eculizumab appears to inhibit the production of activated terminal complement proteins which destroy paroxysmal nocturnal haemoglobinuria (PNH) red blood cells that lack complement protection [202] .
In C5-deficient mice reconstituted with human C5, eculizumab potently inhibited the complement system when administered IV or SC at equivalent doses [207] .
In C5-deficient mice reconstituted with human C5, eculizumab potently inhibited the complement system when administered IV or SC at equivalent doses [207] .
Allergic asthma
a surrogate anti-C5 monoclonal antibody of eculizumab markedly reduced airway hyper-responsiveness compared with placebo in asthmatic mice with established airway inflammation induced by aerosolised methacholine challenge. The reduction was similar to that achieved with corticosteroids. In a mouse model of ongoing asthma attacks, anti-C5 monoclonal antibody improved symptoms when administered either by intravenous injection or as an inhaled aerosol. The antibody was superior to corticosteroids for reducing lung resistance and increasing lung compliance. In bronchial fluid, numbers of white blood cells and the release of inflammatory mediators were significantly reduced by the anti-C5 monoclonal antibody [7] .
In an ex vivo model of pig-to-human xenotransplantation, the addition of eculizumab (50-200 µg/mL) to human blood prior to perfusion dose-dependently prolonged graft survival time compared with no treatment. No signs of hyperacute rejection were observed in the 2 hearts that were perfused with blood containing the highest dose of antibody. Eculizumab reduced total complement activity, and the two higher doses (100 and 200 mg/mL) reduced fluid phase C5b-9 levels compared with no treatment, indicating that the prevention of C5b-9 production correlates with increased heart survival [208] .
Therapeutic Trials
Neuromyelitis optica
Phase III
Updated results from the pivotal phase III PREVENT trial, in patients with anti-aquaporin-4 (AQP4) auto antibody-positive neuromyelitis optica (NMO) demonstrated that in 27 patients (placebo: n=20; eculizumab: n=7) who experienced an independently adjudicated relapse, one relapse led to significantly worse modified Ranking Scale (mRS), Expanded Disability Status Scale (EDSS), 36-item Short-Form Health Survey mental and physical component summary (SF-36 MCS and PCS), and European Quality of Life 5-Dimension questionnaire 3-Level (EQ-5D-3L) visual analogue scale (VAS) and index scores during the study. Relapsing patients exhibited clinically meaningful worsening of disability and HRQoL outcomes within the first 90 days post-relapse, which then did not worsen by 120 days post-relapse. In 4 of 7 outcomes, relapsing patients were more likely to exhibit clinically meaningful worsening than non-relapsing patients. Extrapolation of one relapse to multiple relapses predicted that each relapse led to an incremental worsening of disability, with the EQ-5D utility index score decreasing from 0.7 to 0.3 (-43%) and EDSS score increasing from 4.2 to 5.7 (+35%) after 5 relapses. met its primary endpoint of time to first adjudicated on-trial relapse, demonstrating that treatment with eculizumab reduced the risk of NMO relapse by 94.2% compared with placebo (p < 0.0001). Furthermore, at 96 weeks and 144 weeks, 96.4% of patients treated with eculizumab were free of relapse while only 51.9% and 45.5% of patients administered with placebo were relapse-free. Additionally, amongst 76.2% patients receiving concomitant supportive immunosuppressive therapy, 97.3%, 95.4% and 95.4% were relapse-free at 48 weeks, 96 weeks and 144 weeks, respectively, while 100% of patients not receiving concomitant supportive immunosuppressive therapy, were relapse-free at 48 weeks compared with 61% in the placebo group and the effect was sustained through 96 weeks and 144 weeks. Treatment with eculizumab resulted in improvement in disabilities or no change whereas placebo treated patients showed worsening in disabilities. Mean scores at pre-relapse (n = 24) and post-relapse (n = 22) as per EQ-5D index (possible range, 0–1) were observed to be 0.656 and 0.595 respectively [pre–post difference, –0.067, p= 0.012]. EQ-5D visual analog score (possible range, 0–100) were observed to be 60.458 and 56.500 respectively [pre–post difference, –4.227. Patients who received eculizumab showed mean (SD) change from baseline in EDSS of -0.18 (0.814) compared with 0.12 (0.945) in placebo group (p = 0.0597). Mean (SD) change in modified rankin scale (mRS) from baseline in eculizumab group was -0.2 (0.72) compared with 0.1 (0.75) in placebo group (p = 0.0154). Mean (SD) change in Hauser Ambulation Index (HAI) from baseline in eculizumab group was -0.4 (1.08) compared with 0.5 (1.61) in placebo group (p = 0.0002). By end-of-study, 51% of the eculizumab-treated patients and 42.6% of the placebo-treated patients had no change in EDSS score. By end-of-study, 29.2% of the eculizumab-treated patients and 29.8% of the placebo-treated patients had a 0.5-point improvement in EDSS score, while 19.8% of the eculizumab-treated patients and 27.7% of the placebo-treated patients had a 0.5-point worsening in EDSS score. Significant differences were observed between pre- and post-relapse scores in the SF-36 domains. Results showed that patients worsen after neuromyelitis NMOSD relapses. For all patient data sets analyzed, no significant worsening was observed in the absence of a relapse across all outcomes. These findings were consistent for all assessment timepoints over the 120-week study period for all patients enrolled in trial and for the subset of non-relapsing patients. Similar findings were observed across the 48-week period for the patient population (n = 82) who completed at least 1 year of the study, suggesting these analyses were not influenced by the number of patients completing the study [104] [105] [108] [109] [106] [103] [107] [110] [107]
Phase II
results from an open-label phase I/II trial of eculizumab in 14 patients with severe, relapsing neuromyelitis optica showed that eculizumab significantly reduced the median annualised attack rate, the primary endpoint. The median annualised attack rate before treatment with eculizumab was 3 attacks per patient and this was reduced to 0 attacks per patient during 12 months of chronic eculizumab treatment (p<0.0001). Eighty-six percent (12/14) of patients were free of attacks after 12 months of treatment and 2/14 patients had single "possible" relapses. The study enrolled 14 women (median age: 41 years; range: 18-67 years) who received eculizumab 600mg once-weekly for the first 4 weeks, followed by eculizumab 900mg dose at week-5, and a 900mg maintenance dose q2w thereafter [113] .
Pooled analysis
Pooled data from phase III PREVENT and OLE trial in neuromyelitis optica showed that, eculizumab monotherapy for 85.3 patient-years (PY) found that, adjudicated relapses occurred in 1/33 patients (annualized relapse rate, 0.012; 95% confidence interval [CI]: 0.002–0.082) as compared to placebo treatment (7/13). At 192 weeks, 96.2% of patients receiving eculizumab monotherapy were relapse-free (95% CI: 0.757–0.994) versus 93.8% of patients receiving eculizumab with concomitant IST (95% CI: 0.867–0.972). No patients receiving eculizumab monotherapy required hospitalization for a relapse and none started an IST. Pooled long-term efficacy data from the phase III PREVENT and ECU-NMO-302 trials showed that of 137 evaluable patients, eight eculizumab-treated patients experienced an adjudicated on-trial relapse. Approximately 93.9% (95% CI: 87.5, 97.1) patients remained relapse-free at 192 weeks [100] [101] [107] [102] [111] .
Atypical haemolytic uraemic syndrome (aHUS)
Phase II
two-year outcome data, from two open-label, prospective phase II trials, demonstrated that chronic and sustained treatment with eculizumab inhibited complement-mediated thrombotic microangiopathy (TMA) and significant, continuous time-depended improvements in renal function in patients with aHUS were observed (C08-002A/B, trial 1; C08-003A/B, trial 2). In trial 1, haematological normalisation was increased from 76% of patients at week 26 to 88% at two years, and the mean increase in eGFR from baseline achieved at week 26 was maintained over two years. In trial 2, the proportion of patients that achieved TMA-event free status increased from 80% at week 26 to 95% at two years. Both studies enrolled approximately 15 plasma-resistant and 15 plasma-sensitive patients with aHUS; trial 1 was conducted in adults and trial 2 was conducted in adolescents (age 12 - 18 years) [18] .
Final data from two pivotal phase II studies have demonstrated that eculizumab had significant benefits in patients with atypical haemolytic uraemic syndrome (aHUS), such as improved kidney function, reduced need for interventions (e.g. dialysis) and improved quality of life. In both studies, earlier initiation of eculizumab treatment was associated with significantly greater improvements in kidney function (p < 0.01 for both trials) [44] [26] . In the first study involving 17 adolescents and adults with aHUS who were resistant or intolerant to plasma exchange/infusion, 15 patients received eculizumab for 26 weeks and two patients did not complete the study but were included in the analysis. For the primary endpoint, platelet count increased from baseline through week 26 by a point estimate 73 × 109/L (p = 0.0001). Platelet count was normalised in 13/15 (87%) patients who had abnormal platelets at baseline; 100% of patients who were analysed per protocol achieved normal platelet count. For the secondary endpoints, 15 patients achieved thrombotic microangiopathy (TMA)-event free status (defined as ≥ 12 consecutive weeks of stable or increasing platelet counts, absence of plasma exchange/infusion, and no new dialysis). The median rate of TMA intervention (defined as plasma exchange/infusion or dialysis) decreased from 0.88 events/patient/day to zero (p < 0.0001). Four of five dialysis patients became dialysis-free, and ten patients had sustained improved in chronic kidney disease by ≥ 1 stage. Eight of 17 patients (47%) achieved increased renal function by ≥ 15 mL/min/1.73m2. Furthermore, 80% of patients experienced a significant improvement in health-related quality of life (HRQoL); the mean change in HRQoL from baseline to week 26 of eculizumab therapy was 0.29 (p < 0.002) [44] [26] . In an extension of the phase II study, the primary endpoint of increased platelet counts from baseline was maintained in all 13 patients who entered the extension phase. All 13 patients also sustained their TMA-event free status [185] . The second pivotal study enrolled 20 patients with aHUS who were receiving chronic plasma exchange/infusion. In this 26-week study, 20 patients continued to receive plasma exchange/infusion during an 8-week observation period, and then discontinued plasma exchange/infusion and commenced eculizumab treatment. Patients in the second study received later intervention with eculizumab, compared with patients in the first study (median duration of aHUS from diagnosis to screening of 48 months vs 10 months, respectively). TMA-event free status (primary endpoint) was achieved by 80% of patients in the second study. Key secondary endpoints were also achieved with a high clinical and statistical significance. Platelet count normalisation was achieved by 18/20 (90%) patients, and all patients who had normal baseline platelet counts (17 or 20 patients) maintained that level after discontinuation of plasma exchange/infusion and commencement of eculizumab therapy. A significant reduction in rate of TMA intervention was seen (from 0.23 events/patient/day to zero), and 7 of 20 (35%) patients achieved sustained improvement in chronic kidney disease by ≥ 1 stage. Finally, a significant improvement in QoL was seen in 73% of patients (mean change from baseline to week 26 was 0.11) [44] [26] . These final data were consistent with interim data reported in 2010 [45] . In an extension of the second phase II study detailed above, chronic treatment of patients with a long duration of aHUS, with eculizumab, continued to significantly inhibit complement-mediated TMA and progression of kidney dysfunction. With ongoing eculizumab treatment, there was significant and continuous, time-dependent improvement in eGFR through week 26 and throughout the extension study. The clinically meaningful health benefit in health-related QoL achieved by 73% of patients in the first 26 weeks was maintained with longer term treatment with eculizumab [185] . Data from a long-term extension (n = 32) of the two phase II trials showed that treatment with eculizumab for 2 years was associated with sustained inhibition of complement-mediated TMA in patients with aHUS. This was demonstrated by a maintained increase in platelet count and a sustained improvement in renal function and TMA event-free status [184] .
An additional phase II trial (C10-004) that included 41 adult patients with aHUS generated similar results to previous phase II trials. In this trial, 33 patients (80%) achieved a complete TMA response at one year, meeting the primary endpoint; at 26 week complete TMA response was observed in 73% (30) of patients. Complete platelet normalisation was achieved in 98% of patients. With respect to renal function, eGFR increased significantly from the baseline value of 15 mL/min/1.73m2 (p < 0.0001), with 25 patients (61%) who were on dialysis at baseline able to stop dialysis by one year. At week 26, improvement in eGFR was observed in 22 patients (54%) [48] [49] .
In a 26 weeks post hoc analysis from the C10-004 phase II trial of eculizumab, 100% (21/21) patients and 95% (19/20) with and without an identified genetic mutation, achieved platelet count normalisation, respectively. Of the patients on dialysis at baseline, 78.6% (11/14) patients with an identified mutation, and 90% (9/10) without an identified mutation, discontinued dialysis by 26 weeks. In patients with an identified mutation, the mean change in platelet count was 101 x 109/L, whereas the mean change in patients without an identified mutation was 179 x 109/L. The mean eGFR improvement from baseline in patients with and without identified mutation was +31 mL/min/1.73 m2 and +27 mL/min/1.73 m2 , respectively [47] . In a post-hoc subgroup analysis of C10-004 trial, eculizumab was effective in adult patients with aHUS, independent of dialysis history. A total of 71% (17/24) of patients with baseline dialysis and 77% (13/17) of patients with no baseline dialysis achieved complete TMA response. In patients with baseline dialysis, mean eGFR increased from baseline by +35.0 mL/min/1.73m2 and for those with no baseline dialysis, it improved from baseline by +20.0 mL/min/1.73m2. Another posthoc analysis in adult patients with or without renal transplant indicated that a complete TMA response was observed in 56% (5/9) of transplant patients and in 78% (25/32) of non-transplant patients. A mean eGFR improvement of +31.5 mL/min/1.73m2 from baseline was observed in non-transplant patients and in transplant patients this improvement was of +19.0 mL/min/1.73m2 [48] .
A retrospective evaluation, at three years, of decline in renal function and progression to end stage renal disease (ESRD), revealed that eculizumab improves renal outcomes and eliminates the need of dialysis, in patients with aHUS. Patients treated with eculizumab and supportive care (n = 33) demonstrated a 97% decrease in the risk of progression to ESRD, compared with the progression rate in patients on supportive care only (n = 32). None of the patients in chronic kidney disease (CKD) stage 2 or 3, who were treated with eculizumab, progressed to ESRD; the risk of progression also reduced by 92% in case of CKD 4 stage, compared with those on supportive care only [48] .
In an analysis of biomarker data from a prospective, open-label trial in adult patients with aHUS, treatment with eculizumab resulted in significantly reduced measures of terminal complement activation with reductions in inflammation and endothelial and organ damage. Thrombotic risk was also reduced. Initial treatment with eculizumab was given to 6/41 patients prior to supportive care with either plasma exchange or plasma infusion [18] [182] .
In a 26 weeks post hoc analysis from the C10-003 phase II trial of eculizumab, 100% (11/11) patients and 91% (10/11) with and without an identified genetic mutation, achieved platelet count normalisation, respectively. Of the patients on dialysis at baseline, 100% (5/5) patients with an identified mutation, and 66.7% (4/6) without an identified mutation, discontinued dialysis by 26 weeks. In paediatric patients with an identified mutation, the mean change in platelet count was 172 x 109/L, whereas the mean change in patients without an identified mutation was 154 x 109/L. The mean eGFR improvement from baseline in patients with and without identified mutation was +71 mL/min/1.73 m2 and +57 mL/min/1.73 m2 , respectively [47] . Fourteen of 22 evaluable paediatric patients (64%) had a complete TMA response [primary endpoint] with eculizumab therapy in a prospective phase II trial (C10-003). Patients with aHUS aged >1 month and <18 years received eculizumab over a 26-week treatment period, with nineteen patients completing the planned treatment period. Of the 22 evaluable patients, haematological normalisation was achieved in 95% of patients at a median time of 7 days, and the mean platelet count improvement from baseline was 164 × 109/L (p<0.0001). Significant improvement in renal function was observed. Ten patients who were receiving plasma exchange or infusion (PE/PI) therapy at baseline were able to discontinue PE/PI therapy by the end of the 26-week treatment period. Furthermore, significant improvements in renal function (p < 0.01) and quality of life (p = 0.0001) were achieved [49] . Of the patients on dialysis at baseline, 82% (9/11) discontinued by week 26. A subgroup analysis of patients with or without baseline dialysis revealed that a complete TMA response was observed in 55% (6/11) of the patients with baseline dialysis with a mean eGFR improvement of +57.7 mL/min/1.73m2 from baseline. In 11 patients with no baseline dialysis, complete TMA response was observed in 73% (8) patients and mean eGFR improvement from baseline was +70.3 mL/min/1.73m2. The open-label, phase II study enrolled 22 paediatric patients (age over 1 month) with aHUS. Initial intervention with eculizumab was given to 55% (12/22) of patients prior to supportive care with either plasma exchange or plasma infusion [48] [18] .
Data from a retrospective clinical study of 15 paediatric patients (aged < 12 years) with aHUS, who received ≥ 1 dose of eculizumab outside of prospective clinical trials between 2007 and 2009, were also consistent with data from adult and adolescent trials. Eculizumab significantly reduced TMA incidence, as platelet counts were normalised in 14 patients (93%) and 11 patients (73%) achieved TMA-event free status. Improved renal function was also seen in 53% of patients with eculizumab treatment. Four of six patients with dialysis in the 30 days prior to eculizumab did not require dialysis during eculizumab. Eculizumab efficacy was similar across all paediatric age groups (under 2 years [n = 5], 2 to 4 years [n = 3], 5 to 11 years [n = 7]). The results in this paediatric population were consistent with those from controlled trials in adult and adolescent patients with aHUS in demonstrating that eculizumab controlled TMA, improved kidney function and reduced the need for plasma exchange/infusion [26] .
Subgroup analysis:
Treatment with eculizumab, reversed renal damage and improved haematological markers of complement-mediated thrombotic microangiopathy in a subgroup analysis in patients with aHUS with or without dialysis and a history of kidney transplant. Of the patients on dialysis, 18 of 21 non-transplant patients, two of three transplant patients and 20 of 24 dialysis patients discontinued dialysis. The mean change in platelet count was 132.6 × 109/L (p < 0.0001) in non-transplant patients, 146.2 × 109/L (p = 0.0810) in transplant patients, 163.2 × 109/L (p < 0.0001) in patients on dialysis and 87.4 × 109/L (p = 0.0120) in patients not on dialysis. The mean change from baseline in glomerular filtration rate (eGFR) was 31.5 mL/min/1.73m2 in non-transplant patients (p < 0.0001), 19 mL/min/1.73m2 in transplant patients (p = 0.1940), 35 mL/min/1.73m2 in patients on dialysis (p < 0.0001) and 20 mL/min/1.73m2 in patients not on dialysis (p = 0.0179) [46] .
Subgroup analysis in paediatric patients treated with eculizumab, with or without dialysis, reversed renal damage and improved haematological markers of complement-mediated thrombotic microangiopathy. Approximately 82% of patients on dialysis discontinued dialysis after 26 weeks. The mean improvement in platelet count was 149.8 × 109/L (p = 0.0150) in the dialysis group and 180.2 × 109/L (p = 0.0003) in patients not on dialysis. Mean change in eGFR for the dialysis group was 57.7 mL/min/1.73m2 (p = 0.0568) and for the non-dialysis group was 70.3 mL/min/1.73m2 (p = 0.0056). The subgroup analysis was carried out in paediatric patients enrolled in a open-label, single-arm prospective study [46] .
Membranous glomerulonephritis
In the double-blind, C99-004 trial, 117 patients with membranous nephritis were randomised to receive either placebo, eculizumab 8 mg/kg every four weeks, or eculizumab 8 mg/kg every two weeks for four months. The primary efficacy endpoint, 24-hour urinary protein, was not significantly different between study groups. However, subset analyses showed that patients who appeared to benefit most clinically also had more complete complement inhibition; an important finding as to the pathology of the disease and to the effectiveness of eculizumab treatment [203] .
In the E99-004 trial, 72 placebo and eculizumab patients with membranous nephritis from trial C99-004 were entered into a pre-planned, open-label extension study designed to provide eculizumab 8 mg/kg every two weeks for 12 months. Eculizumab administration was associated with significant improvements in proteinuria, urinary protein/creatinine ratio, and serum albumin. After 12 months of therapy, urinary protein decreased 42% (p < 0.001), urinary protein/creatinine ratio decreased 45% (p < 0.001), serum cholesterol decreased 10% (p = 0.005), serum triglycerides decreased 16% (p = 0.008), and serum albumin increased 14% (p < 0.001) in the 39 patients for whom one year of follow-up data was available. Remission rate was examined prospectively using the widely employed clinical definition of remission in patients with nephrotic membranous nephritis that requires both a 50% reduction in proteinuria and a 24 hour proteinuria less than 3.5g. For the 55 evaluable E99-004 patients who were treated with eculizumab for six months or longer, eculizumab treatment was associated with a 27% 12-month remission rate by Kaplan-Meier analysis [203] .
Shiga-toxin-producing E. coli haemolytic uraemic syndrome (STEC-HUS)
Eculizumab was associated with rapid and sustained clinical outcomes in patients who developed Shiga-toxin-producing E. coli haemolytic uraemic syndrome (STEC-HUS) during an outbreak in Germany in 2011. The study met its primary efficacy outcome at week 8 with 94% of the 198 patients achieving a complete (80% of patients) or partial (14%) response in vital organ involvement and systemic thrombotic microangiopathy. The overall 94% response rate was sustained to week 28, furthermore the complete response rat improved from 80% to 89% during the period 8-28 weeks [54] .
Combined analysis
in findings from 1047 patients enrolled in an international PNH registry over a period of 22.5 months, patients who received eculizumab had a cumulative incidence of TE of 0.41% at one year and 1.35% at two years, compared with 1.70% and 2.61% in patients who did not receive eculizumab, respectively. The cumulative incidence of mortality in eculizumab-treated patients was 2.31% and 4.21% at one and two years, respectively, while in untreated patients it was 4.40% and 7.01%, respectively [183] .
Combined data from two phase III studies, TRIUMPH and SHEPHERD, showed that eculizumab improved fatigue in 164 patients with paroxysmal nocturnal haemoglobinuria (PNH) independent of improvements in anaemia. Findings indicated that the fatigue experienced by patients with PNH was directly related to red blood cell destruction or haemolysis, as measured by levels of lactate dehydrogenase (LDH). While intravascular haemolysis reduction (decreased LDH) and anaemia improvement (increased haemoglobin) were both significantly associated with fatigue improvement, haemolysis reduction was predictive of an improvement in fatigue that was independent of an improvement in anaemia. Improvement in fatigue was significantly greater in eculizumab-treated patients with PNH versus erythropoietin-treated anaemic patients with cancer. The magnitude of clinical impact was analysed using standard descriptors for the effect size (ES) measurement of fatigue in both groups: (i) when the haemoglobin level increased, PNH patients on eculizumab had a large improvement in fatigue (ES: +1.0) versus anaemic cancer patients on erythropoietin who had only a small improvement (ES: +0.48); (ii) when haemoglobin levels did not improve, PNH patients on eculizumab had a moderate improvement in fatigue (ES:+0.72), while erythropoietin-treated anaemic patients with cancer had fatigue scores that did not change meaningfully (ES:+0.15); and (iii) importantly, even when haemoglobin levels decreased, eculizumab-treated patients with PNH still experienced a moderate improvement in fatigue (ES: +0.61), while erythropoietin-treated anaemic patients with cancer had a slight worsening of fatigue (ES:-0.33) [195] [196] .
Analysis of data from 195 patients enrolled in phase II and III trials, including the TRIUMPH and SHEPHERD trials, showed that eculizumab for up to 54 months reduced haemolysis in all patients and reduced thromoboembolism by 92% (3 versus 39 events during the same period prior to treatment) [198] .
An analysis of data collected in clinical trials from 49 patients with both PNH and thrombocytopenia demonstrated administration of eculizumab to increased platelet count by inhibiting terminal complement-mediated platelet activation and consumption. Among thrombocytopenic patients with PNH treated with eculizumab, median platelet counts increased significantly from 68 x 109/L at baseline to 80 and 85 x 109/L (p < 0.001) at 26 and 52 weeks, respectively. Treatment with eculizumab was associated with a reversal of thrombocytopenia in a significant proportion of patients studied, with 33% of previously thrombocytopenic patients improving to a non-thrombocytopenic condition at week 26, and 36% at 52 weeks. Although patients showed significant improvements in platelet counts, there was no change in absolute neutrophil count from baseline to week 26 or week 52, suggesting that the improvements in platelet counts with eculizumab were likely not due to improvement in underlying marrow blood cell production, but rather to reduced platelet consumption associated with terminal complement inhibition. Treatment with eculizumab also markedly inhibited terminal complement activity in all thrombocytopenic patients, as measured by a significant reduction in LDH at 26 and 52 weeks (p < 0.0001 for each time point vs baseline. Administration of eculizumab significantly increased platelet counts irrespective of a history of bone marrow failure (p < 0.05 vs baseline at 52 weeks) or history of thromboembolic events (p < 0.03 vs baseline in both history and no history of thrombosis) [190] .
Breakthrough haemolysis in patients with PNH was successfully managed through eculizumab dose modification. Three of the 195 patients treated in phase II and III trials of eculizumab did not experience consistent blocking of complement-mediated haemolysis with the standard dosing regimen (600 mg/week for 4 weeks; 900mg one week later, 900mg every 14±2 days). Two dosing regimens were successfully employed to maintain complement inhibition in these three patients; both included a maintenance phase with 1200mg every 14 days. One regimen also included an induction period of 900mg weekly for five doses [192] .
An analysis of the phase III TRIUMPH and SHEPHERD trials, evaluating data from 39 patients who were diagnosed with PNH and had a history of aplastic anaemia (AA) or myelodysplastic syndromes (MDS), showed that haemolysis was reduced by 84% following 26 weeks of treatment, compared with a reduction of 85% among patients without a history of AA or MDS [199] .
The primary endpoint of a reduction in intravascular haemolysis was met in the phase III, SHEPHERD trial in patients with PNH. In this open-label trial, 97 patients received eculizumab for 52 weeks. A significant reduction in intravascular haemolysis, as measured by the median LDH area under the curve, was observed after treatment with eculizumab; LDH levels were significantly reduced by 87% after 52 weeks of treatment. A significant decrease in transfusion requirements from a median of 8.0 units of packed red cells in the 12-month pre-treatment period to 0.0 units was seen after eculizumab treatment. A total of 51% of patients were transfusion independent during the 52-week treatment period. A significant 44% increase in endogenous red blood cell mass and a significant increase in haemoglobin levels from 9.2-10.2 g/dL after 12 months of eculizumab therapy were also observed. Fatigue, as measured by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale, significantly improved within one week of eculizumab treatment and was maintained throught the 52 weeks. Significant improvements were also achieved for global health status and fatigue score, as measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) [194] [213] [133] [135] .
Eculizumab achieved all pre-specified primary and secondary endpoints in the phase III, TRIUMPH trial with statistical significance. The median transfusion rate for placebo was 10 units/patient compared with 0 units/patient for eculizumab. There were no patients in the placebo group who achieved haemoglobin stabilisation, compared with 49% of patients in the eculizumab group. Patients treated with eculizumab experienced a 50%reduction in the incidence of pulmonary arterial hypertension (PAH) over the course of the 26-week treatment period, from 52.5% to 26.3%, while PAH did not change with placebo (39.4% to 43.8%) (p < 0.001). Additionally, eculizumab-treated PNH patients experienced significantly improved shortness of breath compared to placebo, as measured by the EORTC QLQ-C30 quality of life survey (p < 0.001) [194] [131] .
Long-term data
long-term treatment with eculizumab for up to 10 years significantly reduced intravascular haemolysis by 83.4%, as assessed by levels of LDH (p<0.001) in patients with PNH from the UK. The survival of PNH patients was slightly inferior to a normal healthy population group and the causes of death were related to bone marrow failure and not due to haemolysis or TE associated with the underlying PNH. In 22 patients who had thrombotic episodes in the 12 months prior to beginning treatment, no further episodes were reported while receiving eculizumab. To date, only 3 TE events were reported in 3 patients. Among patients still receiving transfusions in the most recent 12 months on treatment, a 69% reduction in the number of units transfused was observed [183] . Results from 3, 5.5 and 8 years were previously reported [186] [187] .
Phase II
data from the 26-week extension of the AEGIS phase II study showed that all patients with PNH with chronic kidney disease (CKD) either stabilised or improved, after a total of 38 weeks of treatment with eculizumab. The drug was also associated with a sustained reduction in haemolysis (as evidenced by 87% decrease in LDH from baseline), leading to further improvement in fatigue, maintained improvement in anaemia and reduction in transfusion requirements. The extension study enrolled 27 patients who received eculizumab 600mg every seven days (±2 days) for four weeks; 900mg one week later; then 900mg every 14 days (±2 days). At week 38, 33% (9/27) of patients demonstrated improvement in CKD, 67% showed no change from baseline and no patient worsened (p < 0.05). In addition, 53% (9/17) of patients with CKD (8 with stage 1-2 CKD; 1 with stage 3-5 CKD at baseline) showed improvement from baseline [191] .
The primary efficacy endpoint of change in haemolysis was achieved in the phase II AEGIS trial which demonstrated an 86% reduction in haemolysis (p < 0.001). The study was open labeled and conducted in 29 patients in Japan. Key secondary endpoints including fatigue (p < 0.001) and transfusions/anaemia (p < 0.001) were also achieved. Haemolysis was rapidly and significantly reduced with treatment. Lactate dehydrogenase decreased 86% from a median of 1 814U/L at baseline to 244U/L following 12 weeks of treatment. The control of haemolysis resulted in an improvement in anaemia as indicated by a reduction in packed red blood cell (PRBC) transfusion requirements. Transfusions were reduced 71% during the 12-week pre-treatment period following 12 weeks of eculizumab treatment (p < 0.001 for the pre-specified median change). Transfusion independence was achieved in 67% of patients who were transfusion dependent prior to treatment (p < 0.001). Haemoglobin levels increased from a median of 7.6 g/dL at baseline to a median of 9.0 g/dL following 12 weeks of eculizumab treatment (p < 0.001). An exploratory analysis was also performed to evaluate the effect of eculizumab on Chronic Kidney Disease (CKD), measured as an improvement or worsening in CKD stage during treatment according to the KDOQI CKD published guidelines. Chronic eculizumab treatment was associated with a 12-fold likelihood of an improvement in CKD level (p < 0.001;CKD) improved in 41% (12/29) of patients, CKD was unchanged in 55% (16/29), CKD worsened in 3.4 percent (1/29) [193] [210] .
Further results from the phase II AEGIS study showed that eculizumab improved dyspnoea and other significant morbidities of disease, independent of anaemia; there was significant improvement in dyspnoea within 1 week of treatment with eculizumab and the improvement was sustained throughout the study [188] .
Subset and post-hoc analyses
a post-hoc analysis of data from controlled trials of eculizumab in patients with PNH who were receiving concomitant immunosuppressive therapy showed that treatment with eculizumab was associated with a significant reduction in haemolysis. Mean LDH of 1368 U/L at three months prior to eculizumab treatment was reduced to 389 U/L at three months following initiation of treatment and was maintained to 379 U/L for at least one year (p = 0.002 for both three and 12 months). The treatment also reduced transfusion requirements from a mean of 17 transfusion units/year to a mean of 6 transfusions/year at 12 months prior to and following initiation of eculizumab treatment, respectively (p = 0.02). Mean haemoglobin levels were 9.2 Hgb g/dL and 9.1 Hgb g/dL at 12 months prior to and following initiation of eculizumab treatment, respectively. Eculizumab was also associated with significant improvements in fatigue scores; mean FACIT-Fatigue Scores were 26.8 and 36.3 at 12 months prior to and following initiation of eculizumab treatment, respectively (p = 0.02). The analysis included a population of 195 patients, 17 of which were receiving IST. Patients were subdivided into groups comprising those who commenced eculizumab during ongoing IST and those who commenced IST during ongoing eculizumab treatment [189] .
In patients with PNH that had never-transfused or minimally transfused, administration of eculizumab was demonstrated to significantly reduce haemolysis following for a median of 16 months, as measured by a median reduction in LDH from 1 500 U/L before treatment to 356 U/L after treatment (p = 0.008). Overall, haemoglobin levels increased significantly from 9.0 g/dL before treatment to 10.7 g/dL after treatment (p = 0.0003), with a median increase of 2.0 g/dL. Analysis of a subset of 21 patients previously enrolled in eculizumab clinical trials who had received zero or one transfusion in the year prior to eculizumab treatment demonstrated a significant reduction in haemolysis following six months of eculizumab therapy, with a median reduction in LDH from 2 030 U/L before treatment to 336 U/L after treatment (p < 0.001). Haemoglobin levels increased significantly from 9.0 g/dL before treatment to 10.7 g/dL after treatment (p = 0.0003), with a median increase of 1.7 g/dL. Fatigue was also significantly improved (p < 0.001) [141] .
Preliminary results from an ongoing study demonstrated that among seven patients with PNH and thrombocytopenia with platelet counts below 100 x 109/L prior to eculizumab treatment, a sustained platelet recovery above 100 000 occurred in four of these patients during treatment with the drug for periods ranging from two to 20 months. Levels of D-Dimer and TAT were elevated in all of the patients with thrombocytopenia prior to treatment, and decreased following eculizumab therapy [141] .
According to a clinical trial, eculizumab therapy reduced haemolysis, fatigue, thromboses and transfusion requirements in patients with PNH, including those who might have been expected to have less severe disease when baseline characteristics were considered. In patients with the lowest quartile of haemolysis (< 1490 U/L), LDH was significantly reduced from 1077 ± 42 U/L at baseline to 323 ± 22 U/L during the first six months, and to 347 ± 47 U/L during the next six months of therapy. Haemolysis was also significantly reduced during both six-months periods of therapy in patients with mild anaemia (haemoglobin of ≥ 10.5 g/L) and minimal transfusion support prior to treatment (0 or 1 transfusion episode in the previous year). Additionally, in patients with the lowest quartile of baseline haemolysis, the incidence of thromboses decreased from 10.8 to 4.5 events per 100 patient years. The rate decreased from 5.2 to 0.8 events per 100 patient years in patients with mild anaemia, and from 4.9 to 0.0 events per 100 patient years in patients with minimal pretreatment transfusion support. Eculizumab treatment was also associated with significant improvements in fatigue, as measured by the FACIT-Fatigue instrument, regardless of the baseline level of haemolysis, anaemia, or pretreatment transfusion requirements. Furthermore, in patients with history of bone marrow failure, units transfused were reduced from a mean of 9.2 ± 1.2 units per patient prior to treatment, to 4.4 ± 1.4 units per patient during the second six-month treatment period [197] .
Phase I
cumulative one year results from an open-label, phase Ib trial showed that eculizumab produced a rapid clinical response within a week of administration that lasted over the course of at least one year. Eculizumab significantly reduced the need for blood transfusions, intravascular haemolysis and haemoglobinuria among 11 patients with PNH. This was accompanied by an associated improvement in the quality of life, which have been maintained for at least one year of continuous treatment. All patients received four once-weekly intravenous (IV) infusions of eculizumab 600mg, followed by a 900mg dose one week later and then by 900mg every other week through week 12. Levels of lactate dehydrogenase were significantly decreased from a mean of 3111 IU/L at baseline to 594 IU/L during treatment. The percentage of PNH type III erythrocytes increased significantly from a mean of 36.7% at baseline to 59.2% at the end of 12 weeks of treatment. In addition, the mean and median transfusion rates were reduced from baseline values of 2.1 and 1.8 units per month, respectively, to 0.6 and 0.0 units per month, respectively, during eculizumab therapy. In nine patients for whom urine scores were assessed, the mean paroxysm rate (defined as the mean number of days in paroxysm per patient per month) was significantly reduced from 2.9 days to 0.12 day. During treatment, there were significant improvements in measurements of the quality of life [142] [216] [201] [202] . Two-year cumulative results from this study showed that eculizumab was associated with statistically significant reductions in haemolysis and in the need for blood transfusions. Two-year results showed the percentage of PNH type III erythrocytes to have increased significantly to 58.9%. The mean and median transfusion rates were reduced to 0.4 and 0.3 units/patient/month, respectively through the 23-26 month treatment period [143] .
In a phase I trial, a single dose of eculizumab up to 8 mg/kg was well tolerated by 24 patients with lupus. A single 8 mg/kg dose of eculizumab was associated with a significant reduction in the incidence of proteinuria, an objective measurement of kidney dysfunction. A single dose of eculizumab potently blocked complement activity in patients for up to two weeks [215] .
Myasthenia Gravis
Phase III
Topline results from the phase III REGAIN study showed that the primary efficacy endpoint of change from baseline in Myasthenia Gravis-Activities of Daily Living Profile (MG-ADL) total score, at week 26, did not reach statistical significance (p = 0.0698) as measured by a worst-rank analysis. Also, 18 of 22 pre-defined endpoints and pre-specified analyses, based on primary and secondary endpoints achieved p-values <0.05. The first prospectively defined secondary efficacy endpoint of change from baseline in Quantitative Myasthenia Gravis (QMG) total score with eculizumab treatment compared with placebo at week 26, achieved a p-value of 0.0129 as measured by a worst-rank analysis. The proportion of patients with at least a 3-point reduction in MG-ADL total score and no rescue therapy, and with at least a 5-point reduction in QMG total score and no rescue therapy from baseline to week 26 with eculizumab treatment compared with placebo achieved p-values of 0.0229 and 0.0018, respectively. Mean change, including sensitivity analysis, from baseline in MG-ADL and QMG scores with eculizumab and placebo at week 26 were -4.2 versus -2.3 (p = 0.0058), and -4.6 versus -1.6 (p = 0.0006), respectively. New secondary efficacy endpoint results showed change from baseline in Myasthenia Gravis Composite (MGC) score (p-value 0.1026) and change from baseline in the 15-item Myasthenia Gravis Quality Of Life (MG-QOL15) (p-value 0.0281) at week 26 both measured by a worst-rank analysis. Whereas pre-specified sensitivity analysis of the MGC and MG-QOL15 endpoints using repeated measures from baseline to week 26 were achieved with p-values of 0.0134 and 0.0010, respectively.The phase III REGAIN study enrolled a total of 125 patients globally [77] [76] [81] .
In eculizumab-treated adults with generalised myasthenia gravis (MG), a numerically larger proportion stopped or decreased the dose of a concomitant immunosuppressive therapy (IST) than started or increased the dose. MG symptom improvement and MG symptom worsening were the most common reasons for stopping/decreasing and starting/increasing IST, respectively. Median eculizumab treatment duration from OLE baseline was 22.7 months (range, 1 day to 37.3 months; 227 patient-years’ exposure). At OLE baseline, 98.3% (115/117) of participants were receiving at least one IST. Thereafter, 67.5% (79/117) stopped or decreased the dose of an IST on 439 occasions in total, most commonly because of MG symptom improvement (46.2% [54/117] of participants on 256/439 occasions), and 53.8% (63/117) started or increased the dose of an IST on 189 occasions, most commonly because of MG symptom worsening (32.5% [38/117] of participants on 89/189 occasions). Previous interim results from the extension phase of the phase III REGAIN study demonstrated significant treatment benefits within 1 to 4 weeks, that were sustained through 52 weeks across the four assessment scales of MG-Activities of Daily Living (MG-ADL), Quantitative MG (QMG), MG Composite (MGC), MG Quality of Life 15 (MG-QoL 15). Results from week 26 of the eculizumab group (n=47-49) showed MG-ADL, QMG, MGC and MG-QoL 15 scores of -5.2 [95% CI: -6.3, -4.2], -5.2 [95% CI: -6.7, -3.6], -10 [95% CI: -12.3, -7.8] and -15.2 [95% CI: -19, -11.3], while the corresponding values for placebo group (n=55-56) were -4.9 [95% CI: -5.8, -4.0], -4.8 [95% CI: -6.4, -3.3], -10 [95% CI: -12.0, -8.0] and -12.9 [95% CI: -16.6, -9.1], respectively. At week 52, the same scores in the eculizumab group (n=20) showed values of -4.4 [95% CI: -6.0, -2.7], -4.5 [95% CI: -6.7, -2.3], -8.8 [95% CI: -11.9, -5.6] and -14.9 [95% CI: --21.7, -8.1], while the corresponding values for the eculizumab/placebo group (n=20) were -5.3 [95% CI: -6.8, -3.7], -6.4 [95% CI: -8.8, -4.0], -10 [95% CI: -13.3, -6.7] and -16.2 [95% CI: -21.3, -11.1] [84] [82] [83] .
In a phase III trial of eculizumab in the treatment of children and adolescents with refractory generalised myasthenia gravis (gMG), least-square mean changes from baseline at week 26 were -5.8 (standard error [SE] 1.2; p=0.0004) for Quantitative Myasthenia Gravis (QMG) total score and -2.3 (SE 0.6; p=0.0017) for MG-ADL total score. Similar changes were observed irrespective of chronic intravenous immunoglobulin treatment. Overall, the primary and all secondary efficacy endpoint analyses met statistical significance at week 1. Improvements were sustained through week 26. Complete terminal complement inhibition was sustained throughout 26 weeks in all patients [17] [75] [74] .
Eculizumab appeared to improve patients' Quantitative Myasthenia Gravis disease severity scores (QMG), relative to placebo, in a phase II cross-over trial in 14 patients (NCT00727194). In the first 16-week treatment period, 6/7 (86%) eculizumab recipients and 4/7 (57%) placebo recipients achieved a three-point reduction in QMG score (primary endpoint). Significant improvement (>4 points) in overall change in QMG score from baseline was -7.92 vs -3.67 for eculizumab and placebo recipients, respectively (secondary endpoint). Eculizumab was administered qw at 600mg IV for 4 weeks, followed by 900mg IV q2w for 14 weeks [85] .
In a multicentre, double-blind, placebo-controlled, ascending-dose trial, 40 patients with rheumatoid arthritis received a single dose of the antibody eculizumab (0.1-8.0 mg/kg). Eculizumab dose-dependently blocked complement activity for ≤ 2 weeks. The highest dose (8.0 mg/kg) significantly reduced C-reactive protein levels (the most objective component of the American College of Rheumatology's disease parameters) whereas in placebo recipients, C-reactive protein increased 24%. Eculizumab also reduced some of the more subjective measures of disease activity, such as tender joint count, swollen joint count, patient's global assessment of disease and patient's global assessment of pain [206] .
In a multicentre study, 209 patients with mild-to-moderate rheumatoid arthritis were randomised to receive IV eculizumab 8 mg/kg weekly for 4 weeks then monthly (induction/monthly group), 8 mg/kg once weekly for 4 weeks then once every 2 weeks (induction/biweekly group) or 8 mg/kg once every 2 weeks (biweekly group), or placebo. After 3 months of treatment, a higher proportion of patients in the induction/monthly, compared with the placebo, group met American College of Rheumatology 20% improvement criteria (ACR 20) (43% vs 20%). Compared with the placebo group, patients in the induction/monthly and induction/biweekly groups had greater reductions from baseline in C-reactive protein levels [205] .
In a double-blind, randomised, placebo-controlled phase IIb trial in 368 patients with chronic rheumatoid arthritis undergoing treatment with methotrexate or leflunomide, eculizumab was administered either once per month or biweekly for six months. Monthly administration caused a significant, moderate improvement in ACR20 (34%), compared with placebo (22%), at six months. In addition, erythrocyte sedimentation rate (ESR) was significantly reduced. Twice-weekly administration of eculizumab did not significantly change ACR20, compared with placebo [170] [200] .
Dermatomyositis
In a phase I pilot trial, 13 patients with dermatomyositis were randomised to receive eculizumab or placebo. Eculizumab was administered intravenously at a dose of 8 mg/kg once a week for five weeks and then once every two weeks for up to two months. An improvement of > 50% in the skin rash score was evident in the majority of drug-treated patients who completed the trial [209] .
Psoriasis
Treatment for two months with eculizumab did not significantly improve Psoriasis Area and Severity Index (PASI) scores in a study in 40 patients with severe psoriasis. However, trends towards improvement were observed in certain measures of disease activity. Haemolytic activity and deposition of activated terminal complement in psoriatic plaques were reduced in a dose-dependent manner [204] .
Delayed-graft function:
In the phase II/III PROTECT study, the incidence of delayed graft function, death, graft loss, or loss to follow-up at 7 days post-transplant was observed as 35.9 % and 41.7 % (p=0.398), in the eculizumab treated group and placebo treated group, respectively. Total 288 patients were treated in the study [162] [166] .
Renal transplant rejection
Graft and patient survival after eculizumab treatment was 88.7% and 97.4%, respectively, after one year in an open-label phase II trial in sensitised deceased-donor kidney transplant recipients with antibody-mediated rejection (AMR). Post-transplant failure occurred in 22.5% patients (18/80) at one year, including a 12.5 percent incidence of AMR, based on locally read biopsies. Based on this data, the investigators believe that eculizumab may be effective in reducing the incidence of acute AMR in these patients, with outcomes similar to those expected for non-sensitised patients [181] .
In an open-label, phase II trial in patients with antibody mediated rejection (AMR) following renal transplantation, eculizumab was associated with a composite efficacy endpoint of post-transplant treatment failure in 18.8% of patients (15/80) at 1 year, with a 10% incidence of AMR. At 1 year graft and patient survival were 87.1% and 97.4%, respectively. The composite efficacy endpoint of week 9 post-transplant failure occurred in 12.5% (10/80) of patients, with a 7.5% rate of AMR (6/80) based on locally read biopsies, compared with the historical 30% rate of AMR expected with best available care in this highly sensitized population. At 1 year, post-transplant failure occurred in 18.8% of patients, including a 10.0% incidence of AMR. At baseline and 1 year, mean creatinine levels were 7.44 mg/dL and 1.80 mg/dL, respectively. The study enrolled 80 patients who received deceased-donor kidney transplants [149] .
The week 9 post-transplantation treatment failure rate was 9.8% and 15.7% in the eculizumab and control arms (P = 0.554), respectively, according to results from a phase II study in living donor kidney transplant recipients requiring desensitisation therapy. The primary endpoint of treatment failure rate was the composite of biopsy-proven antibody mediated rejection (AMR), graft loss, patient death or loss to week 9 follow up [147] .
In recipients of deceased-donor kidneys who received eculizumab for immunosuppression, the 9-week post-transplantation treatment failure rate was 10.6%, including an antibody-mediated rejection(AMR) rate of 6.4%, which was markedly lower than the expected AMR rate of 30%. These were the interim findings from a phase II trial that included 47 sensitised recipients of kidneys from deceased donors. The primary endpoint was the treatment failure rate at 9 weeks, defined as biopsy-proven AMR, Graft loss, patient death and/or loss to follow up, assessed by central laboratory data. The interim data reported were determined using local laboratory data [153] .
Future Events
| Expected Date | Event Type | Description | Updated |
|---|---|---|---|
| 31 Dec 2023 | Regulatory Status | AstraZeneca anticipates a regulatory decision for Myasthenia gravis (IV) in China in the second half of 2023 [71] | 23 Aug 2022 |
| 24 Aug 2023 | Trial Update | Alexion in collaboration with AstraZeneca plans the phase IIIb Soliris trial for Haemolytic uraemic syndrome (In adolescents, In adults, In children, In infants, In the elderly) in China (IV) (NCT05876351) (700364460) | 16 Aug 2023 |
| 03 Jul 2023 | Trial Update | Alexion in collaboration with AstraZeneca plans a phase III (Soliris) trial for Paroxysmal Nocturnal Hemoglobinuria (Treatment Naïve) in China (NCT05886244) (700364637) | 18 Jul 2023 |
| 31 Dec 2021 | Trial Update | Alexion Pharmaceuticals plans a phase III trial for Guillain-Barre syndrome in Japan (IV) in 2021 (NCT04752566) (700326012) [13] | 07 May 2021 |
| 30 Jun 2020 | Trial Update | Alexion Pharmaceuticals plans a phase II/III trial for Neuromyelitis optica (In children, In adolescents) in Japan (IV) in the mid 2020 [179] | 10 May 2020 |
| 30 Nov 2019 | Trial Update | Alexion plans a phase II/III trial for Neuromyelitis optica (In children, In adolescents) in USA, Canada, Germany, Italy, Japan, South Korea and Spain November 2019 (IV) (NCT04155424) [180] | 30 Dec 2019 |
| 28 Jun 2019 | Regulatory Status | The US FDA sets PDUFA date of 28/06/2019 for sBLA review for Neuromyelitis optica [91] | 01 Jul 2019 |
| 31 Mar 2019 | Regulatory Status | Alexion announces intention to submit application for the regulatory approval of eculizumab for Neuromyelitis optica in Japan, in first quarter of 2019 [91] | 26 Feb 2019 |
| 31 Dec 2018 | Trial Update | Alexion Pharmaceuticals plans a phase III trial for Myasthenia Gravis in December 2018 (NCT03759366) | 12 Apr 2019 |
| 23 Oct 2017 | Regulatory Status | US FDA accepts sBLA and assigns PDUFA action date of October 23, 2017 for eculizumab for Myasthenia gravis (Treatment-experienced) [66] | 15 Dec 2017 |
| 30 Sep 2017 | Regulatory Status | Alexion expects approval for Myasthenia gravis in European Union in third quarter of 2017 [63] | 15 Sep 2017 |
Development History
| Event Date | Update Type | Comment |
|---|---|---|
| 28 Mar 2024 | Phase Change - No development reported | No recent reports of development identified for clinical-Phase-Unknown development in COVID-19 pneumonia in France (IV) Updated 28 Mar 2024 |
| 28 Mar 2024 | Phase Change - No development reported | No recent reports of development identified for clinical-Phase-Unknown development in COVID-19 pneumonia in USA (IV) Updated 28 Mar 2024 |
| 28 Mar 2024 | Phase Change - No development reported | No recent reports of development identified for clinical-Phase-Unknown development in SARS-COV-2 acute respiratory disease in France (IV) Updated 28 Mar 2024 |
| 28 Mar 2024 | Phase Change - No development reported | No recent reports of development identified for clinical-Phase-Unknown development in SARS-COV-2 acute respiratory disease in USA (IV) Updated 28 Mar 2024 |
| 29 Nov 2023 | Trial Update | Cedars-Sinai Medical Center in collaboration with Alexion Pharmaceuticals terminates a phase II trial in Preeclampsia (In adolescents, In the elderly, In adults) in USA (IV) due to PI moved institutions (NCT04725812) Updated 08 Dec 2023 |
| 06 Nov 2023 | Trial Update | Alexion Pharmaceuticals completes phase III trial in Myasthenia gravis (In children, In adolescents, Treatment-experienced) in Japan, USA, Germany, Netherlands (IV) (NCT03759366) (EudraCT-2016-001384-37) Updated 29 Dec 2023 |
| 05 Nov 2023 | Financial Update | Credit Suisse financial data update Updated 05 Nov 2023 |
| 18 Oct 2023 | Phase Change - Registered | Registered for Neuromyelitis optica (In adults) in China (IV) [89] Updated 20 Oct 2023 |
| 18 Oct 2023 | Trial Update | Alexion terminated terminates phase III PREVENT trial in Neuromyelitis optica in the US, Australia, Canada, Croatia, Colombia, Czech Republic, Denmark, France, Germany, Hong Kong, Italy, Japan, Malaysia, South Korea, Russia, Singapore, Spain, Taiwan, Turkey, the UK, Argentina, Austria and Thailand (NCT01892345) Updated 20 Oct 2023 |
| 24 Aug 2023 | Phase Change - Marketed | Launched for Myasthenia gravis (In adolescents, In children, Treatment-experienced) in Japan (IV) [17] Updated 29 Aug 2023 |
| 24 Aug 2023 | Phase Change - Registered | Registered for Haemolytic uraemic syndrome (In adults, In children, In the elderly, In adolescents) in China (IV) [17] Updated 29 Aug 2023 |
| 24 Aug 2023 | Phase Change - Registered | Registered for Myasthenia gravis (Treatment-experienced, In adolescents, In children) in Japan (IV) [17] Updated 29 Aug 2023 |
| 24 Aug 2023 | Phase Change - Registered | Registered for Paroxysmal nocturnal haemoglobinuria (Treatment-naive) in China (IV) [17] Updated 29 Aug 2023 |
| 27 Jul 2023 | Phase Change - Registered | Registered for Myasthenia gravis (In children, Treatment-experienced, In adolescents) in European Union, Norway, Liechtenstein, and Iceland (IV) [72] Updated 28 Jul 2023 |
| 14 Jul 2023 | Phase Change - III | Phase-III clinical trials in Haemolytic uraemic syndrome (In children, In adolescents, In adults, In the elderly) in China (IV) (NCT05876351) Updated 16 Aug 2023 |
| 05 Jul 2023 | Phase Change - III | Phase-III clinical trials in Paroxysmal nocturnal haemoglobinuria (Treatment-naive) in China (IV, infusion) (NCT05886244) Updated 18 Jul 2023 |
| 26 Jun 2023 | Phase Change - Preregistration | Preregistration for Myasthenia gravis (In children, In adolescents, Treatment-experienced) in European Union (IV) before June 2023 [73] Updated 28 Jun 2023 |
| 26 Jun 2023 | Regulatory Status | Committee for Medicinal Products for Human Use (CHMP) of the EMA recommends expanded use of eculizumab for Myasthenia gravis (In children, In adolescents, Treatment experienced) in European Union [73] Updated 28 Jun 2023 |
| 26 Jun 2023 | Scientific Update | Updated adverse events data from a phase III trial in Myasthenia gravis released by AstraZeneca [73] Updated 28 Jun 2023 |
| 13 Jun 2023 | Phase Change - Registered | Registered for Myasthenia gravis in China (IV) [70] Updated 18 Jun 2023 |
| 02 Jun 2023 | Trial Update | Alexion in collaboration with AstraZeneca plans a phase III (Soliris) trial for Paroxysmal Nocturnal Hemoglobinuria (Treatment Naïve) in China (NCT05886244) Updated 18 Jul 2023 |
| 25 May 2023 | Trial Update | Alexion in collaboration with AstraZeneca plans the phase IIIb Soliris trial for Haemolytic uraemic syndrome (In adolescents, In adults, In children, In infants, In the elderly) in China (IV) (NCT05876351) Updated 16 Aug 2023 |
| 22 Apr 2023 | Scientific Update | Efficacy and adverse events data from a phase III trial in Myasthenia gravis presented at the 75th Annual Meeting of the American Academy of Neurology (AAN-2023) [75] Updated 16 Jun 2023 |
| 26 Aug 2022 | Trial Update | Alexion Pharmaceuticals completes a phase III trial in Guillain-Barre syndrome (Adjunctive-treatment) in Japan (IV) (NCT04752566) Updated 05 Sep 2022 |
| 23 Aug 2022 | Regulatory Status | AstraZeneca anticipates a regulatory decision for Myasthenia gravis (IV) in China in the second half of 2023 [71] Updated 23 Aug 2022 |
| 29 Jul 2022 | Phase Change - Preregistration | Preregistration for Myasthenia gravis in China (IV) [71] Updated 23 Aug 2022 |
| 10 Mar 2022 | Active Status Review | Phase III trial is still ongoing for Myasthenia gravis (In children, In adolescents, Treatment-experienced) in Japan, USA, Germany, Netherlands (IV) (NCT03759366) (EudraCT-2016-001384-37) Updated 10 Mar 2022 |
| 10 Mar 2022 | Active Status Review | Phase-II/III clinical trials is still ongoing for Neuromyelitis optica (In children, In adolescents) in USA, Canada, Germany, Italy, Japan, Spain (IV) (NCT04155424) Updated 10 Mar 2022 |
| 13 Oct 2021 | Scientific Update | Efficacy data from a phase III PREVENT trial in Neuromyelitis optica presented at the 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis [110] Updated 21 Dec 2021 |
| 13 Oct 2021 | Scientific Update | Efficacy data from phase III PREVENT trial presented at the 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-2021) [104] Updated 21 Dec 2021 |
| 27 Sep 2021 | Trial Update | Alexion Pharmaceuticals completes an expanded-access programme for COVID-19 pneumonia and SARS-COV-2 acute respiratory disease (IV) (NCT04802083) Updated 13 Oct 2021 |
| 24 Sep 2021 | Biomarker Update | Biomarkers information updated Updated 02 Oct 2021 |
| 13 Sep 2021 | Phase Change - II | Phase-II clinical trials in Preeclampsia (In adolescents, In adults, In the elderly) in USA (IV) (NCT04725812) Updated 29 Sep 2021 |
| 21 Jul 2021 | Company Involvement | Alexion Pharmaceuticals has been acquired by AstraZeneca and changed its name to Alexion AstraZeneca Rare Disease Updated 29 Jul 2021 |
| 12 Jul 2021 | Trial Update | Alexion Pharmaceuticals completes an open-label extension (OLE) phase III trial in Neuromyelitis optica in USA, Australia, Argentina, Austria, Canada, Colombia, Croatia, Czech Republic, Denmark, Hong Kong, Italy, Japan, Malaysia, South Korea, Russia, Germany, Spain, Taiwan, Thailand, Turkey, France, and United Kingdom (IV) (NCT02003144) (EudraCT2013-001151-12) Updated 21 Apr 2022 |
| 17 Apr 2021 | Scientific Update | Long-term pooled efficacy and safety data from the phase III PREVENT and OLE trials Neuromyelitis optica presented at 73rd Annual Meeting of the American Academy of Neurology (AAN-2021) [100] Updated 27 Jun 2021 |
| 17 Mar 2021 | Trial Update | Alexion Pharmaceuticals initiates an expanded-access programme for COVID-19 pneumonia and SARS-COV-2 acute respiratory disease (IV) (NCT04802083) Updated 24 Mar 2021 |
| 09 Mar 2021 | Trial Update | Alexion Pharmaceuticals completes a emergency Expanded Access Programs in SARS-COV-2 acute respiratory disease and COVID-19 pneumonia in USA, France (IV) (NCT04355494) Updated 15 Mar 2021 |
| 01 Feb 2021 | Phase Change - III | Phase-III clinical trials in Guillain-Barre syndrome (Adjunctive-treatment) in Japan (IV) [15] Updated 07 May 2021 |
| 07 Oct 2020 | Phase Change - III | Phase-III clinical trials in Myasthenia gravis (In children, In adolescents, Treatment-experienced) in Germany, Netherlands (IV) (EudraCT-2016-001384-37) Updated 08 Dec 2021 |
| 30 Jul 2020 | Trial Update | Alexion Pharmaceuticals plans a phase III trial for Guillain-Barre syndrome in Japan (IV) in 2021 (NCT04752566) [13] Updated 07 May 2021 |
| 01 Jun 2020 | Regulatory Status | Eculizumab receives SAKIGAKE designation for Gullain Barre Syndrome in Japan [13] Updated 06 Aug 2020 |
| 06 May 2020 | Trial Update | Alexion Pharmaceuticals plans a phase II/III trial for Neuromyelitis optica (In children, In adolescents) in Japan (IV) in the mid 2020 [179] Updated 10 May 2020 |
| 25 Apr 2020 | Scientific Update | Updated safety data from a pooled analysis of the phase III PREVENT and OLE trials in Neuromyelitis optica presented at the 72nd Annual Meeting of the American Academy of Neurology (AAN-2020) [101] Updated 18 May 2020 |
| 20 Apr 2020 | Phase Change - Clinical | Clinical trials in COVID-19 pneumonia in USA, France (IV) [10] (NCT04355494) Updated 17 Dec 2020 |
| 20 Apr 2020 | Phase Change - Clinical | Clinical trials in SARS-COV-2 acute respiratory disease in USA, France (IV) [10] (NCT04355494) Updated 17 Dec 2020 |
| 05 Mar 2020 | Scientific Update | Efficacy data from a phase III PREVENT trial in Neuromyelitis optica presented at the 72nd Annual Meeting of the American Academy of Neurology (AAN-2020) [105] Updated 18 May 2020 |
| 14 Jan 2020 | Phase Change - II/III | Phase-II/III clinical trials in Neuromyelitis optica (In children, In adolescents) in USA, Canada, Germany, Italy, Spain (IV) (NCT04155424) Updated 08 Dec 2021 |
| 23 Dec 2019 | Phase Change - II/III | Phase-II/III clinical trials in Neuromyelitis optica (In adolescents, In children) in Japan (IV) (NCT04155424) Updated 30 Dec 2019 |
| 23 Nov 2019 | Phase Change - Marketed | Launched for Neuromyelitis optica (In adults, In the elderly) in Japan (IV) [93] Updated 26 Nov 2019 |
| 22 Nov 2019 | Phase Change - Registered | Registered for Neuromyelitis optica (In adults, In the elderly) in Japan (IV) [93] Updated 26 Nov 2019 |
| 11 Sep 2019 | Scientific Update | Pooled efficacy and safety data from the phase III PREVENT trial and open-label extension (OLE) trial in Neuromyelitis optica presented at the 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-2019) [102] Updated 23 Jan 2020 |
| 11 Sep 2019 | Scientific Update | Updated efficacy data from the phase III PREVENT trial in Neuromyelitis optica presented at the 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-2019) [109] [108] Updated 23 Jan 2020 |
| 29 Aug 2019 | Phase Change - Marketed | Launched for Neuromyelitis optica in Czech Republic, Netherlands, Spain, United Kingdom (IV) [95] Updated 18 Sep 2019 |
| 29 Aug 2019 | Phase Change - Registered | Registered for Neuromyelitis optica in Iceland (IV) [95] Updated 13 Sep 2019 |
| 29 Aug 2019 | Phase Change - Registered | Registered for Neuromyelitis optica in Liechtenstein (IV) [95] Updated 13 Sep 2019 |
| 29 Aug 2019 | Phase Change - Registered | Registered for Neuromyelitis optica in Norway (IV) [95] Updated 13 Sep 2019 |
| 29 Aug 2019 | Phase Change - Registered | Registered for Neuromyelitis optica in European Union (IV) [95] Updated 29 Aug 2019 |
| 29 Jul 2019 | Regulatory Status | The Committee for Medicinal Products for Human Use recommends approval of Eculizumab for Neuromyelitis optica in European union [96] Updated 31 Jul 2019 |
| 24 Jul 2019 | Trial Update | Alexion plans a phase II/III trial for Neuromyelitis optica (In children, In adolescents) in USA, Canada, Germany, Italy, Japan, South Korea and Spain November 2019 (IV) (NCT04155424) [180] Updated 30 Dec 2019 |
| 15 Jul 2019 | Phase Change - Marketed | Launched for Neuromyelitis optica in USA (IV) [90] Updated 15 Jul 2019 |
| 27 Jun 2019 | Phase Change - Registered | Registered for Neuromyelitis optica in USA (IV) [90] Updated 01 Jul 2019 |
| 04 May 2019 | Scientific Update | Interim efficacy data from an open-label phase III extension trial for Myasthenia gravis presented at the 71st Annual Meeting of the American Academy of Neurology (AAN-2019) [84] Updated 21 Nov 2019 |
| 03 May 2019 | Scientific Update | Positive efficacy and adverse events data from the phase III PREVENT trial in Neuromyelitis released by Alexion Pharmaceuticals [106] Updated 21 May 2019 |
| 02 May 2019 | Trial Update | Alexion Pharmaceuticals terminates a phase II trial in Delayed graft function (Prevention) in USA as modified to a larger multicenter study to better assess efficacy (IV) (NCT01403389) Updated 15 May 2019 |
| 26 Apr 2019 | Phase Change - Preregistration | Preregistration for Neuromyelitis optica in Japan (IV) [94] Updated 29 Apr 2019 |
| 08 Mar 2019 | Trial Update | Alexion Pharmaceuticals completes an open-label phase III extension trial for Myasthenia gravis in Belgium, Italy, the UK, Germany, Sweden, Hungary, Spain, the Netherlands, Denmark, Czech Republic, and Finland (EudraCT2013-002191-41) Updated 22 Jul 2019 |
| 22 Feb 2019 | Regulatory Status | The US FDA sets PDUFA date of 28/06/2019 for sBLA review for Neuromyelitis optica [91] Updated 01 Jul 2019 |
| 22 Feb 2019 | Regulatory Status | Alexion announces intention to submit application for the regulatory approval of eculizumab for Neuromyelitis optica in Japan, in first quarter of 2019 [91] Updated 26 Feb 2019 |
| 22 Feb 2019 | Regulatory Status | Eculizumab receives priority review status for Neuromyelitis optica in USA [91] Updated 26 Feb 2019 |
| 22 Feb 2019 | Regulatory Status | US FDA accepts sBLA for eculizumab for Neuromyelitis Optica for review [91] Updated 26 Feb 2019 |
| 05 Feb 2019 | Phase Change - Preregistration | Preregistration for Neuromyelitis optica in European Union, USA (IV) [92] Updated 06 Feb 2019 |
| 21 Dec 2018 | Phase Change - III | Phase-III clinical trials in Myasthenia gravis (In children, In adolescents, Treatment-experienced) in Japan, USA (IV) (NCT03759366) Updated 12 Apr 2019 |
| 30 Nov 2018 | Trial Update | Alexion Pharmaceuticals plans a phase III trial for Myasthenia Gravis in December 2018 (NCT03759366) Updated 12 Apr 2019 |
| 24 Sep 2018 | Regulatory Status | Alexion Pharmaceuticals announces intention to file regulatory applications for Neuromyelitis Optica in USA, European Union and Japan [103] Updated 01 Oct 2018 |
| 24 Sep 2018 | Scientific Update | Safety and efficacy data from the phase III PREVENT trial in Neuromyelitis optica released by Alexion Pharmaceuticals [103] Updated 01 Oct 2018 |
| 01 Jul 2018 | Trial Update | Alexion completes the phase-III PREVENT trial in Neuromyelitis optica in USA, Australia, Canada, Croatia, Colombia, Czech Republic, Denmark, France, Germany, Hong Kong, Italy, Japan, Malaysia, South Korea, Russia, Singapore, Spain, Taiwan, Turkey, United Kingdom, Argentina, Austria and Thailand (IV) (NCT01892345) Updated 03 Sep 2018 |
| 27 Apr 2018 | Trial Update | Alexion Pharmaceuticals completes enrolment in the (PREVENT study) Phase III trial for Neuromyelitis optica spectrum disorder Updated 02 May 2018 |
| 23 Apr 2018 | Patent Information | Alexion has patents pending for eculizumab in Brazil [177] Updated 25 Apr 2018 |
| 31 Dec 2017 | Phase Change - Marketed | Launched for Myasthenia gravis (Treatment-experienced) in Japan (IV), prior to December 2017 Updated 13 Feb 2018 |
| 31 Dec 2017 | Phase Change - Marketed | Launched for Myasthenia gravis (Treatment-experienced, In adults) in Germany (IV), prior to December 2017 Updated 13 Feb 2018 |
| 26 Dec 2017 | Phase Change - Registered | Registered for Myasthenia gravis (Treatment-experienced) in Japan (IV) [62] Updated 27 Dec 2017 |
| 06 Nov 2017 | Patent Information | The Japanese Patent Office issues patent No. 6 224 059 for eculizumab [174] Updated 08 Nov 2017 |
| 04 Nov 2017 | Phase Change - No development reported | No recent reports of development identified for preclinical development in Heart-transplant-rejection(Prevention) in USA (Parenteral) Updated 04 Nov 2017 |
| 23 Oct 2017 | Phase Change - Marketed | Launched for Myasthenia gravis (Treatment-experienced) in USA (IV) [65] Updated 15 Nov 2017 |
| 23 Oct 2017 | Phase Change - Registered | Registered for Myasthenia gravis (Treatment-experienced) in USA (IV) [65] Updated 28 Oct 2017 |
| 12 Oct 2017 | Trial Update | Mayo Clinic in collaboration with Alexion Pharmaceuticals terminates a phase I/II trial for Renal transplant rejection (Prevention) in USA (IV) (NCT01106027) Updated 21 Nov 2017 |
| 13 Sep 2017 | Scientific Update | Interim efficacy data from a phase III extension study of the phase III REGAIN trial in Myasthenia gravis released by Alexion Pharmaceuticals [82] Updated 15 Sep 2017 |
| 21 Aug 2017 | Phase Change - Registered | Registered for Myasthenia gravis (Treatment-experienced, In adults) in Iceland, Norway, Liechtenstein (IV) [69] Updated 26 Nov 2019 |
| 21 Aug 2017 | Phase Change - Registered | Registered for Myasthenia gravis (Treatment-experienced, In adults) in European Union (IV) [69] Updated 22 Aug 2017 |
| 15 Aug 2017 | Patent Information | Alexion Pharmaceuticals has patent protection for eculizumab in USA [175] Updated 17 Aug 2017 |
| 15 Aug 2017 | Patent Information | Alexion Pharmaceuticals has patents pending for eculizumab for Paroxysmal nocturnal haemoglobinuria in Europe and Japan, as well as applications for additional indications such as Myasthenia gravis [175] Updated 17 Aug 2017 |
| 01 Aug 2017 | Trial Update | Alexion Pharmaceuticals completes a phase II trial in Renal transplant rejection (Prevention) in USA (IV) (NCT00670774) Updated 13 Jul 2018 |
| 23 Jun 2017 | Regulatory Status | Alexion expects approval for Myasthenia gravis in European Union in third quarter of 2017 [63] Updated 15 Sep 2017 |
| 23 Jun 2017 | Regulatory Status | Committee for Medicinal Products for Human Use (CHMP) of the EMA recommends approval of eculizumab for Myasthenia gravis in European Union [63] Updated 30 Jun 2017 |
| 23 Jun 2017 | Regulatory Status | Japanese Ministry of Health, Labour and Welfare accepts sNDA for eculizumab for Myasthenia gravis for review [63] Updated 30 Jun 2017 |
| 24 May 2017 | Trial Update | Alexion completes a phase II trial for Renal transplant rejection (prevention) in Australia, France, Italy, Spain, Sweden and United Kingdom (NCT01567085) Updated 21 Sep 2017 |
| 22 Mar 2017 | Phase Change - Preregistration | Preregistration for Myasthenia gravis (Treatment-experienced) in Japan (IV) [64] Updated 23 Mar 2017 |
| 08 Mar 2017 | Regulatory Status | US FDA accepts sBLA and assigns PDUFA action date of October 23, 2017 for eculizumab for Myasthenia gravis (Treatment-experienced) [66] Updated 15 Dec 2017 |
| 09 Jan 2017 | Phase Change - Preregistration | Preregistration for Myasthenia gravis (Treatment-experienced) in European Union and USA (IV) [67] Updated 12 Jan 2017 |
| 21 Dec 2016 | Scientific Update | Efficacy and adverse events data from a phase II/III trial in Delayed graft function (Prevention) released by Alexion [162] Updated 26 Dec 2016 |
| 17 Nov 2016 | Licensing Status | Handok extends market licensee contract for eculizumab in South Korea [2] Updated 06 Jun 2017 |
| 01 Nov 2016 | Trial Update | Chiba University completes a phase II trial in Guillain-Barre syndrome in Japan (IV) (NCT02493725) Updated 08 Jun 2017 |
| 01 Nov 2016 | Trial Update | Alexion Pharmaceuticals completes the phase II/III PROTECT trial in Delayed graft function (Prevention) in USA, Australia, Canada, Czech Republic, France, Germany, Italy, Spain (NCT02145182) Updated 03 Mar 2017 |
| 27 Oct 2016 | Regulatory Status | Alexion announces intention to submit regulatory submissions for myasthenia gravis to USA and Europe [68] Updated 07 Nov 2016 |
| 13 Jul 2016 | Trial Update | Alexion Pharmaceuticals terminates its phase II trial for Renal transplant rejection (prevention) in USA, Australia, United Kingdom, France, Germany, Italy, Netherlands, Norway, Sweden & Spain (NCT01399593) Updated 28 Jul 2016 |
| 07 Jul 2016 | Scientific Update | Secondary efficacy endpoint data from the phase III REGAIN trial in Myasthenia Gravis released by Alexion Pharmaceuticals [77] Updated 11 Jul 2016 |
| 17 Jun 2016 | Trial Update | Alexion completes its REGAIN phase III trial in Myasthenia gravis (Treatment-experienced) in USA, Australia, Belgium, Brazil, Canada, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Italy, Japan, South Korea, Netherlands, Spain, Sweden, Turkey and United Kingdom (NCT01997229) Updated 27 Jun 2016 |
| 06 Jun 2016 | Scientific Update | Topline efficacy and adverse events data from the phase III REGAIN trial in Myasthenia Gravis released by Alexion showed that the study failed to meet its primary efficacy endpoint [76] Updated 14 Jun 2016 |
| 30 Apr 2016 | Trial Update | The Brigham and Women's Hospital in collaboration with Alexion terminates a phase II trial in Renal transplant rejection in USA due to lack of efficacy (NCT01895127) Updated 13 Jun 2016 |
| 07 Nov 2015 | Scientific Update | Adverse events data from a post-hoc analysis of three clinical trials in Haemolytic uraemic syndrome released by Alexion Pharmaceuticals [181] Updated 05 Jan 2016 |
| 07 Nov 2015 | Scientific Update | Efficacy and adverse events data from a phase II trial in Renal transplant rejection released by Alexion Pharmaceuticals [181] Updated 05 Jan 2016 |
| 02 Jul 2015 | Licensing Status | Alexion Pharmaceuticals has expanded the large-scale product supply agreement with Lonza Biologics Updated 05 Jul 2015 |
| 01 Jul 2015 | Phase Change - II | Phase-II clinical trials in Guillain-Barre syndrome in Japan (IV) (NCT02493725) Updated 09 Oct 2015 |
| 01 Jul 2015 | Trial Update | Alexion completes enrolment in its REGAIN phase III trial in Myasthenia gravis (Second line therapy or greater) in USA, Australia, Belgium, Brazil, Canada, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Italy, Japan, South Korea, Netherlands, Spain, Sweden, Turkey and United Kingdom (NCT01997229; 10-Q, July 2015) Updated 06 Aug 2015 |
| 27 Jun 2015 | Regulatory Status | The UK's NICE publishes evidence summary for the use of eculizumab to prevent the recurrence of Dense deposit disease [12] Updated 29 Jun 2015 |
| 18 Jun 2015 | Trial Update | Mayo Clinic in collaboration with Alexion Pharmaceuticals terminates a phase I/II trial for Renal transplant rejection (Prevention) in USA (NCT01095887) Updated 09 Jul 2015 |
| 05 May 2015 | Scientific Update | Efficacy and adverse events data from a phase II trial in Renal transplant rejection released by Alexion [149] Updated 12 Jun 2015 |
| 27 Feb 2015 | Regulatory Status | CHMP recommends label update of eculizumab for Paraxismal nocturnal haemoglobinuria and Haemolytic uraemic syndrome in European Union, Iceland, Lichtenstein and Norway [21] Updated 03 Mar 2015 |
| 26 Feb 2015 | Regulatory Status | Alexion files for label update for treatment of patients with Paroxysmal nocturnal haemoglobinuria and Haemolytic uraemic syndrome in European Union, Iceland, Lichtenstein and Norway, after February 2015 [21] Updated 03 Mar 2015 |
| 06 Feb 2015 | Active Status Review | Phase-II development is ongoing in USA for Renal transplant rejection (Treatment) , and in USA, United Kingdom, Germany, France, Italy, Netherlands, Norway, Spain, Sweden and Australia for Renal transplant rejection (Prevention) Updated 03 Mar 2015 |
| 06 Feb 2015 | Phase Change - Discontinued(II) | Discontinued - Phase-II for Age-related macular degeneration (IV, Intravitreous), Autoimmune haemolytic anaemia (Parenteral), Motor neuron disease (IV) and Glomerulonephritis (Parenteral), in USA Updated 03 Mar 2015 |
| 06 Feb 2015 | Phase Change - III | Phase-III clinical trials in Delayed graft function (Prevention) in USA, Italy, Spain, Australia, Canada, Czech Republic and Germany (IV) Updated 03 Mar 2015 |
| 31 Jan 2015 | Phase Change - III | Phase-III clinical trials in Neuromyelitis optica in USA, Australia, Argentina, Austria, Canada, Colombia, Croatia, Czech Republic, Denmark, France, Hong Kong, Italy, Japan, Malaysia, South Korea, Russia, Germany, Spain, Taiwan, Thailand, Turkey, and United Kingdom (IV) (NCT02003144) (EudraCT2013-001151-12) Updated 03 Sep 2018 |
| 28 Jan 2015 | Regulatory Status | The UK's National Institute for Health and Care Excellence (NICE) issues final guidance recommending eculizumab for atypical Haemolytic uraemic syndrome [34] Updated 03 Feb 2015 |
| 07 Jan 2015 | Scientific Update | Efficacy data from a phase II study in Renal transplant rejection (Prevention) released by Alexion Pharmaceuticals [147] Updated 09 Jan 2015 |
| 10 Dec 2014 | Regulatory Status | Eculizumab receives Orphan Drug status for Myasthenia gravis in Japan [88] Updated 12 Dec 2014 |
| 08 Dec 2014 | Scientific Update | Efficacy and adverse events data from the C10-003 phase II trial in Haemolytic uraemic syndrome presented at the 56th Annual Meeting of the American Society of Haematology (ASH-2014) [47] Updated 02 Jan 2015 |
| 08 Dec 2014 | Scientific Update | Efficacy and adverse events data from the C10-004 phase II trial in Haemolytic uraemic syndrome presented at the 56th Annual Meeting of the American Society of Haematology (ASH-2014) [47] Updated 02 Jan 2015 |
| 27 Nov 2014 | Regulatory Status | The UK's National Institute for Health and Care Excellence issues final draft guidance recommending eculizumab for atypical Haemolytic Uraemic Syndrome [33] , [32] Updated 30 Nov 2014 |
| 25 Nov 2014 | Regulatory Status | Eculizumab receives Orphan Drug status for Neuromyelitis optica in Japan [99] Updated 27 Nov 2014 |
| 18 Nov 2014 | Phase Change - III | Phase-III clinical trials in Myasthenia gravis in Belgium, Finland, Germany, Greece and the Netherands (IV) Updated 18 Nov 2014 |
| 15 Nov 2014 | Scientific Update | Efficacy and adverse event data from a subgroup analysis of phase II trial (NCT01193348) in Haemolytic uraemia syndrome released by Alexion Pharmaceuticals [48] Updated 19 Nov 2014 |
| 15 Nov 2014 | Scientific Update | One-year efficacy, safety and pharmacodynamics data and sub-group analysis data from a phase II trial (NCT01194973) in Haemolytic uraemic syndrome released by Alexion Pharmaceuticals [48] Updated 18 Nov 2014 |
| 11 Nov 2014 | Phase Change - Marketed | Launched for Paroxysmal nocturnal haemoglobinuria (In children, In adults, In adolescents) in Belgium, Austria, Denmark, France, Germany, Ireland, Italy, Poland, Portugal, Sweden, Netherlands, Spain, Czech Republic, Norway, New Zealand, Argentina, United Kingdom, Luxembourg, Russia, Mexico, Finland and Taiwan (IV) prior to November 2014 Updated 03 Mar 2015 |
| 17 Oct 2014 | Trial Update | Alexion Pharmaceuticals initiates enrolment in a phase III extension trial for Myasthenia gravis in Belgium, Italy, the UK, Germany, Sweden, Hungary, Spain, the Netherlands, Denmark, Czech Republic, and Finland (EudraCT2013-002191-41) Updated 18 Nov 2014 |
| 25 Aug 2014 | Phase Change - II/III | Phase-II/III clinical trials in Delayed graft function (Prevention) in Czech Republic (IV) (NCT02145182) after August 2014 Updated 03 Jan 2015 |
| 25 Aug 2014 | Phase Change - II/III | Phase-II/III clinical trials in Delayed graft function (Prevention) in USA (IV) Updated 28 Aug 2014 |
| 14 Aug 2014 | Phase Change - Marketed | Launched for Haemolytic uraemic syndrome (In children, In adolescents, In infants, In adults) in Czech Republic (IV) prior to August 2014 Updated 03 Mar 2015 |
| 12 Aug 2014 | Phase Change - II/III | Phase-II/III clinical trials in Delayed graft function (Prevention) in Australia (IV) (NCT02145182) after August 2014 Updated 03 Jan 2015 |
| 12 Aug 2014 | Phase Change - II/III | Phase-II/III clinical trials in Delayed graft function (Prevention) in Canada (IV) (NCT02145182) after August 2014 Updated 03 Jan 2015 |
| 12 Aug 2014 | Phase Change - II/III | Phase-II/III clinical trials in Delayed graft function (Prevention) in Germany & Spain (IV) Updated 22 Sep 2014 |
| 01 Aug 2014 | Regulatory Status | Eculizumab receives Orphan Drug status for Myasthenia gravis in European Union Updated 05 Aug 2014 |
| 01 Jul 2014 | Phase Change - II/III | Phase-II/III clinical trials in Delayed graft function (Prevention) in France (IV) Updated 13 Apr 2015 |
| 17 Jun 2014 | Regulatory Status | Eculizumab receives Orphan Drug status for Myasthenia gravis in USA Updated 19 Jun 2014 |
| 11 Jun 2014 | Scientific Update | Efficacy and adverse event data from a subgroup analysis in Haemolytic uraemic syndrome released by Alexion Pharmaceuticals [46] Updated 11 Jun 2014 |
| 23 May 2014 | Trial Update | Alexion plans a phase II/III trial for Delayed graft function (prevention) in USA, Australia, Brazil, Canada and Europe (NCT02145182) Updated 11 Jun 2014 |
| 07 May 2014 | Phase Change - Marketed | Launched prior to May 2014 for atypical Haemolytic uraemic syndrome in Israel, Netherlands and Spain (IV) Updated 07 May 2014 |
| 07 May 2014 | Regulatory Status | US FDA grants conversion of accelerated approval to regular approval of eculizumab for treatment of atypical Haemolytic uraemic syndrome (in adults and children) in the USA [18] Updated 07 May 2014 |
| 05 May 2014 | Trial Update | Alexion Pharmaceuticals initiates an expanded access programme EMBRACE for Paroxysmal nocturnal haemoglobinuria in USA (NCT00438789) Updated 19 Jun 2017 |
| 05 May 2014 | Scientific Update | Final efficacy data from a phase II trial in atypical Haemolytic uraemic syndrome released by Alexion [18] Updated 07 May 2014 |
| 05 May 2014 | Scientific Update | Final adverse events and efficacy data from a phase II trial in atypical Haemolytic uraemic syndrome (in infants, children and adolescents) released by Alexion [18] Updated 07 May 2014 |
| 05 May 2014 | Scientific Update | Two year outcome adverse events and efficacy data from two phase II trials in atypical Haemolytic uraemic syndrome (in adolescents and adults) released by Alexion [18] Updated 07 May 2014 |
| 29 Apr 2014 | Phase Change - Marketed | Launched for Haemolytic uraemic syndrome in Japan (IV) prior to April 2014 Updated 03 Mar 2015 |
| 25 Apr 2014 | Trial Update | Alexion reinitiates enrolment in a phase II trial for Renal transplant rejection (prevention) in Australia, France, Italy, Spain, Sweden and the United Kingdom (NCT01567085) Updated 02 May 2014 |
| 23 Apr 2014 | Regulatory Status | Eculizumab receives Orphan Drug status for Transplant rejection (prevention) in European Union [160] Updated 28 Apr 2014 |
| 24 Feb 2014 | Regulatory Status | Eculizumab receives Orphan Drug status for Delayed graft function (prevention) in European Union Updated 25 Feb 2014 |
| 03 Feb 2014 | Phase Change - III | Phase-III clinical trials in Myasthenia gravis in Denmark (IV) Updated 19 Jun 2014 |
| 01 Feb 2014 | Trial Update | Alexion completes a phase II trial in Haemolytic uraemic syndrome in USA, Belgium, France, Germany, Italy, Spain and United Kingdom (NCT01194973) Updated 01 Jun 2015 |
| 27 Jan 2014 | Trial Update | Alexion Pharmaceuticals completes enrolment in its phase II trial for Renal transplant rejection (prevention) in USA, Australia, United Kingdom, France, Germany, Italy, Netherlands, Norway, Sweden & Spain (NCT01399593) Updated 19 Mar 2014 |
| 21 Jan 2014 | Regulatory Status | Eculizumab receives Orphan Drug status for Delayed graft function (prevention) in USA Updated 22 Jan 2014 |
| 01 Jan 2014 | Phase Change - III | Phase-III clinical trials in Neuromyelitis optica in Croatia, Colombia, Denmark, Czech Republic, Malaysia (IV) (NCT01892345) Updated 31 Oct 2017 |
| 01 Jan 2014 | Phase Change - III | Phase-III clinical trials in Neuromyelitis optica in Australia, Canada, France, Germany, Hong Kong, Italy, Japan, South Korea, Russia, Singapore, Taiwan, Turkey and United Kingdom (IV) (NCT01892345) Updated 27 Nov 2014 |
| 01 Jan 2014 | Phase Change - III | Phase-III clinical trials in Neuromyelitis optica in USA (IV) (NCT01892345) Updated 28 Apr 2014 |
| 31 Dec 2013 | Phase Change - III | Phase-III clinical trials in Myasthenia gravis in USA (IV) Updated 28 Apr 2014 |
| 08 Dec 2013 | Scientific Update | Efficacy data from a phase II trial in Haemolytic uraemic syndrome released by Alexion Pharmaceuticals [182] Updated 20 Dec 2013 |
| 02 Dec 2013 | Trial Update | Alexion Pharmaceuticals plans a global phase III trial for Myasthenia gravis (NCT01997229) Updated 05 Dec 2013 |
| 01 Dec 2013 | Phase Change - III | Phase-III clinical trials in Myasthenia gravis (Treatment-experienced) in Australia, Brazil, Czech Republic, France, Hungary, Turkey and South Korea (IV) after December 2013 (NCT01997229) Updated 06 Aug 2015 |
| 01 Dec 2013 | Trial Update | Alexion Pharmaceuticals completes two phase II trials in Haemolytic uraemic syndrome in North America and Europe (NCT00838513; NCT00844428) Updated 02 Feb 2015 |
| 01 Dec 2013 | Phase Change - III | Phase-III clinical trials in Myasthenia gravis in Canada, Japan, Italy, Spain, Sweden and the United Kingdom after December 2013 (IV) Updated 14 May 2014 |
| 30 Nov 2013 | Phase Change - II | Phase-II clinical trials in Renal transplant rejection in USA (IV) Updated 27 Dec 2013 |
| 09 Nov 2013 | Scientific Update | Efficacy and adverse events data from phase II trials in adults and in paediatric patients with Haemolytic uraemic syndrome released by Alexion Pharmaceuticals [49] Updated 28 Nov 2013 |
| 17 Oct 2013 | Phase Change - III | Phase-III clinical trials in Neuromyelitis optica (relapsing) in Spain (IV) Updated 27 Nov 2013 |
| 17 Oct 2013 | Trial Update | Alexion Pharmaceuticals initiates enrolment in a phase III extension trial for Neuromyelitis optica (relapsing) in Spain (EudraCT2013-001151-12) Updated 27 Nov 2013 |
| 25 Sep 2013 | Trial Update | Alexion Pharmaceuticals completes a phase II trial for Haemolytic uraemic syndrome in Japan (NCT01757431) Updated 21 Mar 2017 |
| 17 Sep 2013 | Phase Change - Marketed | Launched for Paroxysmal nocturnal haemoglobinuria in Israel (IV) prior to September 2013 Updated 03 Mar 2015 |
| 13 Sep 2013 | Phase Change - Registered | Registered for Haemolytic uraemic syndrome in Japan (IV) Updated 17 Sep 2013 |
| 11 Sep 2013 | Scientific Update | Interim efficacy and adverse events data from a phase II trial in Renal transplant rejection released by Alexion Pharmaceuticals [153] Updated 18 Sep 2013 |
| 31 Aug 2013 | Regulatory Status | Eculizumab receives Orphan Drug status for Neuromyelitis optica in European Union Updated 28 Feb 2014 |
| 07 Aug 2013 | Trial Update | Icahn School of Medicine at Mount Sinai and Alexion Pharmaceuticals plan a phase II trial for Delayed graft function (prevention) in USA (NCT01919346) Updated 16 Aug 2013 |
| 01 Aug 2013 | Trial Update | Icahn School of Medicine at Mount Sinai and Alexion Pharmaceuticals initiates enrolment in a phase II trial for Delayed graft function (prevention) in USA (NCT01919346) Updated 11 Jun 2014 |
| 25 Jul 2013 | Phase Change - II | Phase-II clinical trials in Renal transplant rejection (prevention) in Sweden prior to July 2013 (IV) Updated 09 Aug 2013 |
| 25 Jul 2013 | Trial Update | Alexion Pharmaceuticals completes enrolment in its phase II trial for Renal transplant rejection (prevention) in Australia, France, Italy, Spain, Sweden and the United Kingdom (NCT01567085) Updated 09 Aug 2013 |
| 19 Jul 2013 | Trial Update | The Brigham and Women's Hospital in collaboration with Alexion plans a phase II trial in Renal transplant rejection in USA (NCT01895127) Updated 19 Jul 2013 |
| 16 Jul 2013 | Regulatory Status | The Committee for Orphan Medicinal Products of the EMA recommends eculizumab be granted orphan designation for Neuromyelitis optica in European Union [98] Updated 17 Jul 2013 |
| 01 Jul 2013 | Trial Update | Alexion Pharmaceuticals completes two phase II trials in Haemolytic uraemic syndrome in North America and Europe (NCT00844844; NCT00844545) Updated 02 Feb 2015 |
| 01 Jul 2013 | Trial Update | Alexion Pharmaceuticals plans a phase III trial for Neuromyelitis optica in USA (NCT01892345) Updated 15 Jul 2013 |
| 27 Jun 2013 | Regulatory Status | Eculizumab receives Orphan Drug status for Neuromyelitis optica in USA Updated 01 Jul 2013 |
| 25 Jun 2013 | Phase Change - No development reported(II) | No development reported - Phase-II for Antiphospholipid syndrome in USA (Parenteral) Updated 25 Jun 2013 |
| 21 Jun 2013 | Scientific Update | Final efficacy data from Phase-II trials in atypical Haemolytic uraemic syndrome released by Alexion [44] Updated 21 Jun 2013 |
| 21 May 2013 | Phase Change - Registered | Registered for Paroxysmal nocturnal haemoglobinuria (in children) in European Union (IV) Updated 30 Jun 2013 |
| 06 Mar 2013 | Phase Change - Marketed | Launched for Haemolytic uraemic syndrome (In adults, In children, In adolescents, In infants) in Canada (IV) Updated 15 Nov 2017 |
| 06 Mar 2013 | Phase Change - Registered | Registered for atypical Haemolytic uraemic syndrome (in adolescents, in adults, in children) in Canada (Parenteral) Updated 08 Mar 2013 |
| 23 Jan 2013 | Regulatory Status | The Ministers of Health in the UK recommend against following AGNSS recommendation for use of eculizumab for atypical Haemolytic uraemic syndrome (aHUS) [28] Updated 29 Jan 2013 |
| 10 Dec 2012 | Scientific Update | Efficacy and adverse events data from clinical trials in Paroxysmal nocturnal hemoglobinuria presented at the 54th Annual Meeting of the American Society of Hematology (ASH-2012) [183] Updated 17 Dec 2012 |
| 05 Nov 2012 | Scientific Update | Final efficacy data from a phase II trial in Haemolytic uremic syndrome released by Alexion Pharmaceuticals [54] Updated 19 Nov 2012 |
| 03 Nov 2012 | Scientific Update | Two-year efficacy data from phase II trials in Haemolytic uraemic syndrome presented at the American Society of Nephrology's Kidney Week 2012 Meeting [184] Updated 21 Nov 2012 |
| 09 Oct 2012 | Phase Change - II | Phase-II clinical trials in Renal transplant rejection in Netherlands (IV) Updated 18 Oct 2012 |
| 09 Oct 2012 | Phase Change - II | Phase-II clinical trials in Renal transplant rejection in Norway (IV) Updated 18 Oct 2012 |
| 09 Oct 2012 | Scientific Update | Final efficacy and adverse events data from a phase I/II trial in Neuromyelitis optica presented at the American Neurological Association Annual Meeting (ANA-2012) [113] Updated 18 Oct 2012 |
| 25 Jul 2012 | Trial Update | Alexion Pharmaceuticals plans a trial for severe and refractory Myasthenia gravis [80] Updated 26 Jul 2012 |
| 18 Jul 2012 | Phase Change - II | Phase-II clinical trials in Renal transplant rejection in France (IV) Updated 18 Oct 2012 |
| 18 Jul 2012 | Phase Change - II | Phase-II clinical trials in Renal transplant rejection in Germany (IV) Updated 18 Oct 2012 |
| 18 Jul 2012 | Phase Change - II | Phase-II clinical trials in Renal transplant rejection in Spain (IV) Updated 18 Oct 2012 |
| 18 Jul 2012 | Phase Change - II | Phase-II clinical trials in Renal transplant rejection in United Kingdom (IV) Updated 18 Oct 2012 |
| 21 May 2012 | Phase Change - Marketed | Launched for Haemolytic uraemic syndrome in United Kingdom (Parenteral) before May 2012 Updated 29 Jan 2013 |
| 16 May 2012 | Phase Change - II | Phase-II clinical trials in Haemolytic uraemic syndrome (In children, In adolescents, In adults) in Japan (IV) (NCT01757431) Updated 21 Mar 2017 |
| 01 Apr 2012 | Trial Update | Alexion initiates enrolment in a phase IV trial for eculizumab in patients with Haemolytic uraemic syndrome in USA (NCT01522183) Updated 03 Mar 2015 |
| 16 Mar 2012 | Regulatory Status | The European Medicines Agency grants a positive opinion recommending unlimited validity for eculizumab [22] Updated 30 Mar 2012 |
| 17 Feb 2012 | Active Status Review | Eculizumab is still in phase II trials for Glomerulonephritis in US Updated 27 Feb 2012 |
| 01 Jan 2012 | Phase Change - Marketed | Launched for Haemolytic uraemic syndrome (In adults, In adolescents, In infants, In children) in South Korea (IV) [2] Updated 06 Jun 2017 |
| 01 Jan 2012 | Phase Change - Marketed | Launched for Paroxysmal nocturnal haemoglobinuria in South Korea (IV) [2] Updated 06 Jun 2017 |
| 30 Nov 2011 | Phase Change - Marketed | Launched for Haemolytic uraemic syndrome (In children, In infants, In adolescents, In adults) in European Union (IV) Updated 15 Nov 2017 |
| 30 Nov 2011 | Phase Change - Registered | Registered for Haemolytic uraemic syndrome in European Union (Parenteral) Updated 30 Nov 2011 |
| 11 Nov 2011 | Scientific Update | Long-term efficacy data from extension studies of two phase II trials in atypical Haemolytic uraemic syndrome released by Alexion Pharmaceuticals [185] Updated 15 Nov 2011 |
| 07 Nov 2011 | Trial Update | Alexion Pharmaceuticals initiates enrolment in a phase II trial for the prevention of Renal transplant rejection in the US; expansion to Australia, Canada, England, France, Germany, Italy, the Netherlands and Norway is planned (NCT01399593) Updated 09 Dec 2011 |
| 01 Nov 2011 | Trial Update | Alexion Pharmaceuticals completes a phase I/II trial for Paroxysmal nocturnal haemoglobinuria (In adolescents, In children) in USA (IV) (NCT00867932) Updated 27 Jan 2017 |
| 23 Sep 2011 | Phase Change - Marketed | Launched for Haemolytic uraemic syndrome in USA, for use by adults, adolescents and children (Parenteral) Updated 26 Sep 2011 |
| 23 Sep 2011 | Phase Change - Registered | Registered for Haemolytic uraemic syndrome in USA (Parenteral) Updated 26 Sep 2011 |
| 23 Sep 2011 | Regulatory Status | The Committee for Medicinal Products for Human Use recommends approval of eculizumab for Haemolytic uraemic syndrome in European Union [24] Updated 26 Sep 2011 |
| 15 Sep 2011 | Scientific Update | Efficacy data from a phase II trial in Myasthenia gravis released by Alexion Pharmaceuticals [85] Updated 22 Sep 2011 |
| 31 Aug 2011 | Phase Change - II | Phase-II clinical trials in Delayed graft function (prevention) in USA (IV) Updated 09 Aug 2013 |
| 20 Jun 2011 | Trial Update | Alexion initiates a phase II clinical trial for Shiga-toxin producing E. coli haemolytic uremic syndrome (STEC-HUS) in Germany [52] Updated 22 Jun 2011 |
| 12 Jun 2011 | Scientific Update | Efficacy & adverse events data from a paediatric trial in atypical Haemolytic uraemic syndrome presented at the 16th Congress of the European Haematology Association (EHA-2011) [26] Updated 15 Jun 2011 |
| 12 Jun 2011 | Scientific Update | Final efficacy & adverse events data from two pivotal phase II trials in atypical Haemolytic uraemic syndrome presented at the 16th Congress of the European Haematology Association (EHA-2011) [26] Updated 15 Jun 2011 |
| 12 Jun 2011 | Scientific Update | Efficacy data from a long-term trial in paroxysmal nocturnal hemoglobinuria released by Alexion Pharmaceuticals [186] Updated 14 Jun 2011 |
| 01 Jun 2011 | Regulatory Status | Eculizumab receives priority review status for atypical haemolytic uraemic syndrome in USA [27] Updated 07 Jun 2011 |
| 07 Apr 2011 | Phase Change - Preregistration | Preregistration for Haemolytic uraemic syndrome in European Union (Parenteral) Updated 08 Apr 2011 |
| 07 Apr 2011 | Phase Change - Preregistration | Preregistration for Haemolytic uraemic syndrome in USA (Parenteral) Updated 08 Apr 2011 |
| 21 Mar 2011 | Phase Change - Marketed | Launched for Paroxysmal nocturnal haemoglobinuria in Switzerland (IV) before March 2011 Updated 29 Jan 2013 |
| 25 Feb 2011 | Phase Change - Marketed | Launched for Paroxysmal nocturnal haemoglobinuria in Australia (IV) Updated 25 Feb 2011 |
| 25 Feb 2011 | Phase Change - II | Phase-II clinical trials in Antiphospholipid syndrome in USA (Parenteral) Updated 25 Feb 2011 |
| 25 Feb 2011 | Regulatory Status | Eculizumab receives Orphan Drug status for Paroxysmal nocturnal haemoglobinuria in South Korea Updated 25 Feb 2011 |
| 17 Feb 2011 | Phase Change - II | Phase-II clinical trials in Age-related macular degeneration in USA (Intravitreous) Updated 25 Feb 2011 |
| 17 Feb 2011 | Phase Change - II | Phase-II clinical trials in Autoimmune haemolytic anaemia in USA (Parenteral) Updated 25 Feb 2011 |
| 07 Dec 2010 | Scientific Update | Long-term efficacy data in Paroxysmal nocturnal haemoglobinuria presented at the 52nd Annual Meeting and Exposition of the American Society of Hematology (ASH-2010) [187] Updated 10 Dec 2010 |
| 21 Nov 2010 | Scientific Update | Efficacy and adverse events data from phase II trials in atypical haemolytic uraemic syndrome released by Alexion Pharmaceuticals [45] Updated 24 Nov 2010 |
| 05 Nov 2010 | Trial Update | Alexion Pharmaceuticals initiates enrolment in a phase II trial (NCT01193348) in paediatric patients for atypical haemolytic uraemic syndrome in the US, Canada, and the EU Updated 24 Nov 2010 |
| 23 Oct 2010 | Phase Change - Clinical | Clinical trials in Autoimmune haemolytic anaemia in USA (Parenteral) Updated 25 Feb 2011 |
| 30 Sep 2010 | Phase Change - Marketed | Launched for Paroxysmal nocturnal haemoglobinuria in Japan (IV) Updated 25 Feb 2011 |
| 01 Jul 2010 | Trial Update | Alexion initiates enrolment in a phase II trial for Haemolytic uraemic syndrome in Belgium, France, Germany, Italy, Spain and United Kingdom (NCT01194973) Updated 01 Jun 2015 |
| 13 Jun 2010 | Scientific Update | Efficacy data from the phase AEGIS II trial in Paroxysmal nocturnal haemoglobinuria presented at the 15th Congress of the European Hematology Association (EHA-2010) [188] Updated 23 Jun 2010 |
| 21 Apr 2010 | Trial Update | Alexion Pharmaceuticals completes enrolment in four Phase-II trials for Haemolytic uraemic syndrome in North America and Europe Updated 23 Apr 2010 |
| 16 Apr 2010 | Phase Change - Registered | Registered for Paroxysmal nocturnal haemoglobinuria in Japan (IV) Updated 20 Apr 2010 |
| 01 Mar 2010 | Trial Update | Mayo Clinic in collaboration with Alexion Pharmaceuticals initiates enrolment in a phase I/II trial for Renal transplant rejection (Prevention) in USA (NCT01106027) Updated 09 Jul 2015 |
| 01 Mar 2010 | Trial Update | Mayo Clinic in collaboration with Alexion Pharmaceuticals initiates enrolment in a phase I/II trial for Renal transplant rejection (Prevention) in USA (NCT01095887) Updated 09 Jul 2015 |
| 23 Feb 2010 | Phase Change - Preclinical | Preclinical trials in prevention of Heart transplant rejection in USA (Parenteral) Updated 23 Apr 2010 |
| 23 Feb 2010 | Phase Change - Registered | Registered for Paroxysmal nocturnal haemoglobinuria in South Korea (IV) Updated 23 Apr 2010 |
| 23 Feb 2010 | Phase Change - Registered | Registered for Paroxysmal nocturnal haemoglobinuria in Switzerland (IV) Updated 23 Apr 2010 |
| 31 Dec 2009 | Regulatory Status | Eculizumab receives Orphan Drug status for Haemolytic uraemic syndrome in USA Updated 25 Feb 2011 |
| 07 Dec 2009 | Scientific Update | Efficacy and safety data from analyses of clinical trials in Paroxysmal nocturnal haemoglobinuria presented at the 51st Annual Meeting and Exposition of the American Society of Hematology (ASH-2009) [189] , [190] Updated 09 Dec 2009 |
| 06 Dec 2009 | Scientific Update | Efficacy and adverse events data from the extension study of AEGIS phase II trial in Paroxysmal nocturnal haemoglobinuria presented at the 51st Annual Meeting and Exposition of the American Society of Hematology (ASH-2009) [191] Updated 08 Dec 2009 |
| 07 Aug 2009 | Regulatory Status | Eculizumab received Orphan Drug status for Haemolytic uraemic syndrome in Europe Updated 07 Aug 2009 |
| 07 Aug 2009 | Trial Update | Alexion Pharmaceuticals initiates enrolment in four phase II trials for Atypical Hemolytic Uremic Syndrome in North America and Europe Updated 07 Aug 2009 |
| 31 Jul 2009 | Phase Change - II | Phase-II clinical trials in Age-related macular degeneration in USA (IV) Updated 23 Apr 2010 |
| 29 Jul 2009 | Phase Change - Marketed | Launched for Paroxysmal nocturnal haemoglobinuria in Canada (IV) Updated 31 Jul 2009 |
| 07 Jun 2009 | Scientific Update | Efficacy data from a clinical trial in Paroxysmal nocturnal haemoglobinuria presented at the European Haemotology Association Congress 2009 (EHA-2009) Updated 10 Jun 2009 |
| 01 May 2009 | Phase Change - I/II | Phase-I/II clinical trials in Paroxysmal nocturnal haemoglobinuria (In adolescents, In children) in USA (IV) (NCT00867932) Updated 27 Jan 2017 |
| 30 Apr 2009 | Phase Change - II | Phase-II clinical trials in Neuromyelitis optica in USA (IV) Updated 23 Apr 2010 |
| 01 Apr 2009 | Phase Change - Preregistration | Preregistration for Paroxysmal nocturnal haemoglobinuria in Japan (IV) Updated 03 Apr 2009 |
| 26 Feb 2009 | Phase Change - Registered | Registered for Paroxysmal nocturnal haemoglobinuria in Australia (IV) Updated 02 Mar 2009 |
| 26 Feb 2009 | Regulatory Status | Eculizumab received Orphan Drug status for Paroxysmal nocturnal haemoglobinuria in Canada Updated 02 Mar 2009 |
| 23 Feb 2009 | Phase Change - II | Phase-II clinical trials in Motor neuron disease in USA (IV) Updated 23 Apr 2010 |
| 23 Feb 2009 | Phase Change - II | Phase-II clinical trials in Type II membranoproliferative glomerulonephritis in USA (Parenteral) Updated 23 Apr 2010 |
| 30 Jan 2009 | Phase Change - II | Phase-II clinical trials for atypical haemolytic uraemic syndrome in US (Parenteral) Updated 25 Feb 2011 |
| 30 Jan 2009 | Phase Change - II | Phase-II clinical trials in Haemolytic uraemic syndrome in Canada (Parenteral) Updated 25 Feb 2011 |
| 30 Jan 2009 | Phase Change - Registered | Registered for Paroxysmal nocturnal haemoglobinuria in Canada (IV) Updated 04 Feb 2009 |
| 30 Jan 2009 | Phase Change - II | Phase II trials in Atypical haemolytic uraemic syndrome in Europe (Parenteral) Updated 03 Feb 2009 |
| 14 Jan 2009 | Trial Update | Alexion completes a phase II trial in Allergic asthma in Canada Updated 02 Mar 2009 |
| 13 Jan 2009 | Regulatory Status | Eculizumab received Orphan Drug status for Paroxysmal nocturnal haemoglobinuria in Japan Updated 15 Jan 2009 |
| 01 Jan 2009 | Licensing Status | Eculizumab market-licensed to Handok in South Korea [2] Updated 06 Jun 2017 |
| 31 Dec 2008 | Phase Change - II | Phase-II clinical trials in Myasthenia gravis in United Kingdom (IV) Updated 25 Feb 2011 |
| 09 Dec 2008 | Scientific Update | Efficacy data from a dose-modification study in patients with breakthrough haemolysis presented at the 50th Annual Meeting and Exposition of the American Society of Hematology (ASH-2008) [192] Updated 12 Feb 2009 |
| 09 Dec 2008 | Scientific Update | Adverse events and efficacy data from the AEGIS phase II trial in Paroxysmal nocturnal haemoglobinuria presented at the 50th Annual Meeting and Exposition of the American Society of Hematology (ASH-2008) [193] Updated 21 Jan 2009 |
| 09 Dec 2008 | Scientific Update | Efficacy data from a phase III trial in Paroxysmal nocturnal haemoglobinuria presented at the 50th Annual Meeting and Exposition of the American Society of Hematology (ASH-2008) [194] Updated 15 Dec 2008 |
| 08 Dec 2008 | Scientific Update | Efficacy data from a phase II AEGIS trial in Paroxysmal nocturnal haemoglobinuria presented at the 50th Annual Meeting and Exposition of the American Society of Hematology (ASH-2008) [138] Updated 15 Dec 2008 |
| 07 Dec 2008 | Phase Change - Preclinical | Preclinical trials in Autoimmune haemolytic anaemia in USA (Parenteral) Updated 11 Dec 2008 |
| 31 Oct 2008 | Phase Change - II | Phase-II clinical trials in Myasthenia gravis in Canada (IV) Updated 25 Feb 2011 |
| 31 Oct 2008 | Phase Change - II | Phase-II clinical trials in Myasthenia gravis in USA (IV) Updated 15 Jan 2009 |
| 23 Oct 2008 | Phase Change - Preclinical | Preclinical trials in Antiphospholipid syndrome in USA (Parenteral) Updated 29 Jan 2009 |
| 09 Oct 2008 | Phase Change - II | Phase-II clinical trials in Renal transplant rejection in Italy (IV) Updated 18 Oct 2012 |
| 01 Oct 2008 | Trial Update | Alexion Pharmaceuticals completes a phase III trial for Paroxysmal nocturnal haemoglobinuria in USA, Australia, Belgium, Canada, France, Germany, Ireland, Italy, Netherlands, Spain, Sweden and United Kingdom (NCT00122317) Updated 07 Jun 2017 |
| 30 Sep 2008 | Phase Change - Preregistration | Preregistration for Paroxysmal nocturnal haemoglobinuria in Switzerland (IV) Updated 04 Feb 2009 |
| 15 Jun 2008 | Scientific Update | Efficacy data from a combined analysis of two phase III (TRIUMPH and SHEPHERD) trials in patients with Paroxysmal nocturnal haemoglobinuria presented at the 13th Congress of the European Haematology Association (EHA-2008) [195] , [196] Updated 17 Jun 2008 |
| 31 Mar 2008 | Phase Change - II | Phase-II clinical trials in Renal transplant rejection in Australia (Parenteral) Updated 26 Jul 2010 |
| 31 Mar 2008 | Phase Change - II | Phase-II clinical trials in prevention of Renal transplant rejection in USA (Parenteral) Updated 15 Jan 2009 |
| 25 Mar 2008 | Trial Update | Alexion Pharmaceuticals completes enrolment in the AEGIS trial for Paroxysmal nocturnal haemoglobinuria in Japan Updated 26 Mar 2008 |
| 07 Jan 2008 | Phase Change - III | Phase-III clinical trials in Paroxysmal nocturnal haemoglobinuria in Japan (IV) Updated 09 Jan 2008 |
| 31 Dec 2007 | Phase Change - Marketed | Launched for Paroxysmal nocturnal haemoglobinuria in European Union (IV) Updated 04 Feb 2009 |
| 31 Dec 2007 | Phase Change - Preclinical | Preclinical trials in Motor neuron disorders in USA (Parenteral) Updated 26 Mar 2008 |
| 31 Dec 2007 | Phase Change - Preclinical | Preclinical trials in Myasthenia gravis in USA (Parenteral) Updated 26 Mar 2008 |
| 31 Dec 2007 | Phase Change - Preregistration | Preregistration for Paroxysmal nocturnal haemoglobinuria in Australia (IV) Updated 26 Mar 2008 |
| 11 Dec 2007 | Scientific Update | Interim efficacy data from a clinical trial in Paroxysmal nocturnal haemoglobinuria presented at the American Society of Hematology 49th Annual Meeting and Exposition (ASH-2007) [197] Updated 19 Dec 2007 |
| 30 Sep 2007 | Phase Change - II | Phase-II clinical trials in Asthma in Canada (IV) Updated 26 Mar 2008 |
| 22 Aug 2007 | Scientific Update | Results from clinical trials in Paroxysmal nocturnal haemoglobinuria added to the Haemotological Disorders therapeutic trials section [198] Updated 22 Aug 2007 |
| 22 Jun 2007 | Phase Change - Registered | Registered for Paroxysmal nocturnal haemoglobinuria in European Union (IV) Updated 26 Jun 2007 |
| 19 Jun 2007 | Scientific Update | Data presented at the 43rd Annual Meeting of the American Society of Clinical Oncology (ASCO-2007) added to the adverse events and Haemotological Disorders therapeutic trials sections [199] Updated 19 Jun 2007 |
| 27 Apr 2007 | Phase Change - Marketed | Launched for Paroxysmal nocturnal haemoglobinuria in USA (IV) Updated 24 May 2007 |
| 27 Apr 2007 | Regulatory Status | The CHMP recommends approval of eculizumab for Paroxysmal nocturnal haemoglobinuria in the European Union Updated 03 May 2007 |
| 10 Apr 2007 | Regulatory Status | Eculizumab received Orphan Drug status for Paroxysmal nocturnal haemoglobinuria in Australia Updated 24 May 2007 |
| 16 Mar 2007 | Phase Change - Registered | Registered for Paroxysmal nocturnal haemoglobinuria in USA (IV, infusion) Updated 20 Mar 2007 |
| 21 Feb 2007 | Trial Update | Alexion completes a phase III trial in Paroxysmal Nocturnal Hemoglobinuria in USA, Australia, Belgium, Canada, France, , Netherlands, Switzerland and the UK. (NCT00122304) (EudraCT2004-002795-42) Updated 06 Mar 2023 |
| 12 Jan 2007 | Scientific Update | Data presented at the 48th Annual Meeting and Exposition of the American Society of Hematology (ASH-2006) added to the adverse events and Haematological disorders therapeutic trials sections [133] Updated 12 Jan 2007 |
| 31 Dec 2006 | Phase Change - Preclinical | Preclinical trials in Age-related macular degeneration in USA (Intravitreous) Updated 24 May 2007 |
| 21 Nov 2006 | Phase Change - Discontinued(Preclinical) | Discontinued - Preclinical for Adult respiratory distress syndrome in USA (unspecified route) Updated 21 Nov 2006 |
| 21 Nov 2006 | Phase Change - Discontinued(Preclinical) | Discontinued - Preclinical for Idiopathic thrombocytopenic purpura in USA (unspecified route) Updated 21 Nov 2006 |
| 21 Nov 2006 | Phase Change - Preclinical | Preclinical trials in Transplant rejection in USA (unspecified route) Updated 21 Nov 2006 |
| 21 Nov 2006 | Regulatory Status | Alexion has been granted a priority review for eculizumab by the US FDA Updated 21 Nov 2006 |
| 12 Oct 2006 | Trial Update | Alexion completes the phase III SHEPHERD trial for Paroxysmal nocturnal haemoglobinuria in Germany, Ireland, Italy, Spain, Sweden, and United Kingdom (EudraCT2004-002795-42) Updated 16 Jul 2019 |
| 28 Sep 2006 | Phase Change - Preregistration | Preregistration for Paroxysmal nocturnal haemoglobinuria in European Union (IV-infusion) Updated 28 Sep 2006 |
| 20 Sep 2006 | Phase Change - Preregistration | Preregistration for Paroxysmal nocturnal haemoglobinuria in USA (IV-infusion) Updated 22 Sep 2006 |
| 08 Aug 2006 | Regulatory Status | Eculizumab has received accelerated assessment status for paroxysmal nocturnal haemoglobinuria in Europe Updated 14 Aug 2006 |
| 14 Jun 2006 | Scientific Update | Interim results from a phase III clinical trial (SHEPHERD) in patients with PNH have been added to the adverse events and Haematological Disorders therapeutic trials sections [135] Updated 14 Jun 2006 |
| 15 May 2006 | Phase Change - Preclinical | Preclinical trials in Asthma in USA (unspecified route) Updated 16 Mar 2006 |
| 16 Mar 2006 | Active Status Review | This compound is still in active development for transplant rejection Updated 16 Mar 2006 |
| 31 Jan 2006 | Scientific Update | Data from a media release have been added to the adverse events and Haematological disorders therapeutic trials sections [131] Updated 31 Jan 2006 |
| 26 Sep 2005 | Phase Change - No development reported(Preclinical) | No development reported - Preclinical for Idiopathic thrombocytopenic purpura in USA (unspecified route) Updated 14 Feb 2006 |
| 26 Sep 2005 | Phase Change - Discontinued(I) | Discontinued - Phase-I for Dermatomyositis in USA (unspecified route) Updated 27 Sep 2005 |
| 26 Sep 2005 | Phase Change - Discontinued(I) | Discontinued - Phase-I for Bullous pemphigoid in USA (unspecified route) Updated 26 Sep 2005 |
| 26 Sep 2005 | Phase Change - Discontinued(I) | Discontinued - Phase-I for Psoriasis in USA (unspecified route) Updated 26 Sep 2005 |
| 26 Sep 2005 | Phase Change - Discontinued(II) | Discontinued - Phase-II for Lupus nephritis in USA (unspecified route) Updated 26 Sep 2005 |
| 26 Sep 2005 | Phase Change - Discontinued(II) | Discontinued - Phase-II for Membranous glomerulonephritis in USA (unspecified route) Updated 26 Sep 2005 |
| 26 Sep 2005 | Phase Change - Discontinued(II) | Discontinued - Phase-II for Systemic lupus erythematosus in USA (unspecified route) Updated 26 Sep 2005 |
| 26 Sep 2005 | Phase Change - Discontinued(II/III) | Discontinued - Phase-II/III for Rheumatoid arthritis in Canada (IV-infusion) Updated 26 Sep 2005 |
| 26 Sep 2005 | Phase Change - Discontinued(II/III) | Discontinued - Phase-II/III for Rheumatoid arthritis in USA (IV-infusion) Updated 26 Sep 2005 |
| 23 Sep 2005 | Trial Update | Alexion Pharmaceuticals has completed enrolment in the SHEPHERD trial for Paroxysmal Nocturnal Haemoglobinuria in the US, Canada, Europe and Australia Updated 23 Sep 2005 |
| 18 Jul 2005 | Trial Update | Alexion has completed randomisation in the phase III TRIUMPH trial for paroxysmal nocturnal haemoglobinuria in Australia, Canada, Europe, and the US Updated 14 Feb 2006 |
| 01 May 2005 | Trial Update | Alexion Pharmaceuticals initiates enrolment in a phase III trial for Paroxysmal nocturnal haemoglobinuria in USA, Australia, Belgium, Canada, France, Germany, Ireland, Italy, Netherlands, Spain, Sweden and United Kingdom (NCT00122317) Updated 07 Jun 2017 |
| 12 Apr 2005 | Trial Update | Alexion Pharmaceuticals has completed enrolment in the TRIUMPH trial for Paroxysmal Nocturnal Haemoglobinuria in the US, Canada, Europe and Australia Updated 13 Apr 2005 |
| 16 Feb 2005 | Trial Update | Alexion initiates enrolment in the phase III SHEPHERD trial for Paroxysmal nocturnal haemoglobinuria in Germany, Ireland, Italy, Spain, Sweden, and United Kingdom (EudraCT2004-002795-42) Updated 14 Feb 2006 |
| 07 Dec 2004 | Scientific Update | Data presented at the 46th Annual Meeting and Exposition of the American Society of Hematology (ASH-2004) have been added to the adverse events and Haematological Disorders therapeutic trials sections [143] Updated 26 Jan 2005 |
| 03 Nov 2004 | Trial Update | Alexion has initiated enrolment in the TRIUMPH trial for paroxysmal nocturnal haemoglobinuria in Australia, Canada, Europe and the US. Updated 14 Feb 2006 |
| 03 Nov 2004 | Phase Change - III | Phase-III clinical trials in Paroxysmal nocturnal haemoglobinuria in Australia (IV-infusion) Updated 03 Nov 2004 |
| 03 Nov 2004 | Phase Change - III | Phase-III clinical trials in Paroxysmal nocturnal haemoglobinuria in Canada (IV-infusion) Updated 03 Nov 2004 |
| 03 Nov 2004 | Phase Change - III | Phase-III clinical trials in Paroxysmal nocturnal haemoglobinuria in European Union (IV-infusion) Updated 03 Nov 2004 |
| 03 Nov 2004 | Phase Change - III | Phase-III clinical trials in Paroxysmal nocturnal haemoglobinuria in USA (IV-infusion) Updated 03 Nov 2004 |
| 20 Jul 2004 | Regulatory Status | The US FDA has approved two protocols, under a Special Protocol Assessment (SPA), for the pivotal phase III programme of eculizumab in Paroxysmal Nocturnal Haemoglobinuria Updated 27 Aug 2004 |
| 24 Jun 2004 | Scientific Update | Data presented at the Annual European Congress of Rheumatology (EULAR-2004) have been added to the Rheumatic disease therapeutic trials section [200] Updated 24 Jun 2004 |
| 20 Apr 2004 | Scientific Update | Data from a media release have been added to the adverse events and Haematological Disorders therapeutic trials sections [142] Updated 22 Apr 2004 |
| 31 Mar 2004 | Trial Update | Alexion initiates a phase III trial in Paroxysmal Nocturnal Hemoglobinuria in USA, Australia, Belgium, Canada, France, , Netherlands, Switzerland and the UK. (NCT00122304) (EudraCT2004-002795-42) Updated 06 Mar 2023 |
| 12 Feb 2004 | Scientific Update | Data from a media release have been added to the adverse events and Cancer therapeutic trials sections [201] Updated 12 Feb 2004 |
| 05 Feb 2004 | Phase Change - II | Phase-II clinical trials in Paroxysmal nocturnal haemoglobinuria in European Union (IV) Updated 24 May 2007 |
| 05 Feb 2004 | Phase Change - II | Phase-II clinical trials in Paroxysmal nocturnal haemoglobinuria in USA (IV) Updated 24 May 2007 |
| 28 Jan 2004 | Scientific Update | Data from a media release have been added to the adverse events and Rheumatic Disease therapeutic trials sections [170] Updated 02 Feb 2004 |
| 09 Dec 2003 | Regulatory Status | Eculizumab has received orphan drug status for Paroxysmal nocturnal haemoglobinuria in the EU Updated 09 Dec 2003 |
| 31 Aug 2003 | Regulatory Status | Eculizumab has received orphan drug status for paroxysmal nocturnal haemoglobinuria in the US Updated 14 Feb 2006 |
| 31 Jul 2003 | Phase Change - Suspended(I) | Suspended - Phase-I for Dermatomyositis in USA (unspecified route) Updated 18 Nov 2003 |
| 31 Jan 2003 | Trial Update | Alexion has completed enrolment in a phase IIb trial for rheumatoid arthritis in USA and Canada Updated 05 Feb 2003 |
| 06 Jan 2003 | Company Involvement | Alexion Pharmaceuticals has entered into a large-scale product supply agreement with Lonza Biologics Updated 28 Jan 2003 |
| 11 Dec 2002 | Scientific Update | A study has been added to the adverse events and Haemotological Disorders therapeutic trials sections [202] Updated 11 Dec 2002 |
| 08 Nov 2002 | Scientific Update | Two studies have been added to the adverse events and Genitourinary disorders therapeutic trials sections [203] Updated 08 Nov 2002 |
| 25 Mar 2002 | Trial Update | Enrolment has been completed in a phase II trial for membranous nephritis Updated 25 Mar 2002 |
| 31 Jan 2002 | Trial Update | Alexion has completed a pilot phase I trial in Dermatomyositis in USA Updated 18 Nov 2003 |
| 31 Jan 2002 | Phase Change - II/III | Phase-II/III clinical trials in Rheumatoid arthritis in Canada (unspecified route) Updated 05 Feb 2003 |
| 31 Jan 2002 | Phase Change - II/III | Phase-II/III clinical trials in Rheumatoid arthritis in USA (unspecified route) Updated 05 Feb 2003 |
| 29 Jan 2002 | Trial Update | A phase IIb trial of h5G1.1 has commenced in rheumatoid arthritis Updated 29 Jan 2002 |
| 19 Jun 2001 | Trial Update | Initial results from a pilot study have been added to the adverse events and Skin Disorders therapeutic trials sections [204] Updated 19 Jun 2001 |
| 05 Mar 2001 | Regulatory Status | Eculizumab has received orphan drug status for idiopathic membranous glomerular nephropathy in the USA Updated 25 Mar 2002 |
| 26 Feb 2001 | Scientific Update | A study in patients with rheumatoid arthritis has been added to the Rheumatic Disease therapeutic trials section [205] Updated 26 Feb 2001 |
| 20 Feb 2001 | Phase Change - Preclinical | Preclinical development for Idiopathic thrombocytopenic purpura in USA (Unknown route) Updated 20 Feb 2001 |
| 13 Oct 2000 | Regulatory Status | Eculizumab has received Orphan Drug Status for Dermatomyositis in USA Updated 13 Oct 2000 |
| 05 Oct 2000 | Phase Change - I | Phase-I clinical trials for Bullous pemphigoid in USA (Unknown route) Updated 05 Oct 2000 |
| 05 Oct 2000 | Phase Change - I | Phase-I clinical trials for Dermatomyositis in USA (Unknown route) Updated 05 Oct 2000 |
| 05 Oct 2000 | Phase Change - I | Phase-I clinical trials for Psoriasis in USA (Unknown route) Updated 05 Oct 2000 |
| 31 Aug 2000 | Trial Update | Patient enrolment completed in a phase II efficacy trial of h5G1.1 in rheumatoid arthritis Updated 07 Sep 2000 |
| 18 Apr 2000 | Phase Change - Preclinical | Preclinical development for Bullous pemphigoid in USA (Unknown route) Updated 18 Apr 2000 |
| 10 Mar 2000 | Phase Change - II | Phase-II clinical trials for Lupus nephritis in USA (Unknown route) Updated 10 Mar 2000 |
| 02 Mar 2000 | Regulatory Status | Eculizumab has received fast track status for glomerulonephritis in USA Updated 02 Mar 2000 |
| 07 Feb 2000 | Phase Change - Preclinical | Preclinical development for Dermatomyositis in USA (Unknown route) Updated 07 Feb 2000 |
| 14 Jan 2000 | Phase Change - Preclinical | Preclinical development for Psoriasis in USA (Unknown route) Updated 14 Jan 2000 |
| 06 Oct 1999 | Phase Change - II | Phase-II clinical trials for Membranous glomerulonephritis in USA (Unknown route) Updated 06 Oct 1999 |
| 20 Aug 1999 | Phase Change - I | Phase-I clinical trials for Lupus nephritis in USA (Unknown route) Updated 20 Aug 1999 |
| 28 Jul 1999 | Phase Change - No development reported | No-Development-Reported for Adult respiratory distress syndrome in USA (Unknown route) Updated 28 Jul 1999 |
| 28 Jul 1999 | Phase Change - No development reported | No-Development-Reported for Xenotransplant rejection in USA (Unknown route) Updated 28 Jul 1999 |
| 27 May 1999 | Scientific Update | A study has been added to the adverse events and Rheumatic Disease therapeutic trials sections [206] Updated 27 May 1999 |
| 30 Apr 1999 | Trial Update | Alexion has completed a phase I/II trial in rheumatoid arthritis in the US Updated 14 Feb 2006 |
| 03 Aug 1998 | Phase Change - II | Phase-II clinical trials for Rheumatoid arthritis in USA (Unknown route) Updated 03 Aug 1998 |
| 03 Aug 1998 | Phase Change - II | Phase-II clinical trials for Systemic lupus erythematosus in USA (Unknown route) Updated 03 Aug 1998 |
| 19 May 1998 | Phase Change - Preclinical | Preclinical development for Systemic lupus erythematosus in USA (Unknown route) Updated 19 May 1998 |
| 30 Jan 1998 | Regulatory Status | IND filed in the US for clinical testing of h5G1.1 in rheumatoid arthritis Updated 30 Jan 1998 |
| 16 Jan 1997 | Scientific Update | An in vivo study has been added to the pharmacodynamics section [207] Updated 16 Jan 1997 |
| 22 Aug 1996 | Phase Change - Preclinical | Preclinical development for Lupus nephritis in USA (Unknown route) Updated 22 Aug 1996 |
| 15 Feb 1996 | Phase Change - Preclinical | Preclinical development for Adult respiratory distress syndrome in USA (Unknown route) Updated 15 Feb 1996 |
| 08 Feb 1996 | Phase Change - Preclinical | Preclinical development for Transplant rejection in USA (Unknown route) Updated 08 Feb 1996 |
| 22 Nov 1995 | Phase Change - Preclinical | Preclinical development for Rheumatic disorders in USA (Unknown route) Updated 22 Nov 1995 |
References
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Acquisition of Alexion completed.
Media Release -
Handok strengthens their partnership with Alexion.
Media Release -
Lonza Announces Additional Long-Term Agreement with Alexion.
Media Release -
Alexion Pharmaceuticals Signs Agreement With Lonza Biologics For Commercial Manufacturing.
Media Release -
A Randomized, Double Blind, Placebo-Controlled, Crossover Study to Evaluate the Safety and Efficacy of Eculizumab in Subjects With Mild Allergic Asthma.
ctiprofile -
Alexion Pharmaceuticals' Antibody Therapy Shown Effective in Model for Severe Allergic Asthma.
Media Release -
Alexion Pharmaceuticals Reports the Amelioration of Asthma Symptoms With Anti-C5 Therapy.
Media Release -
SOLIRIS (Eculizumab) for the Treatment of Participants With Coronavirus Disease 2019 (COVID-19) - An Expanded Access Protocol
ctiprofile -
SOLIRIS® (Eculizumab) for the Treatment of Participants With Coronavirus Disease 2019 (COVID 19) - An Expanded Access Program for Hospital-based Emergency Treatment
ctiprofile -
Alexion Announces Plans to Initiate Phase 3 Study of ULTOMIRIS(Rm) (ravulizumab-cwvz) in Hospitalized Patients with Severe COVID-19.
Media Release -
Alexion Statement on SOLIRIS(R) (eculizumab) and COVID-19.
Media Release -
NICE publishes evidence summary on eculizumab (Soliris) for treating rare kidney condition.
Media Release -
Alexion Reports Second Quarter 2020 Results.
Media Release -
A Phase 3, Prospective, Multicenter, Double Blind, Randomized, Placebo Controlled Study to Evaluate the Efficacy and Safety of Eculizumab in Patients With Guillain-Barré Syndrome (GBS)
ctiprofile -
Alexion Reports First Quarter 2021 Results.
Media Release -
A prospective, multicenter, Phase II study to evaluate the safety and efficacy of eculizumab in subjects with Guillain-Barre syndrome
ctiprofile -
Soliris approved in Japan for paediatric patients with generalised myasthenia gravis (gMG).
Media Release -
FDA Approves Conversion of Soliris(R)(eculizumab) Accelerated Approval in aHUS to Regular Approval for the Treatment of Patients with aHUS.
Media Release -
FDA Approves Soliris for Rare Pediatric Blood Disorder.
Media Release -
Soliris(Rm) (eculizumab) Approved by FDA for All Patients with Atypical Hemolytic Uremic Syndrome (aHUS).
Media Release -
Alexion Receives CHMP Positive Opinions for Important Updates to the EU Label for Soliris(Rm) (eculizumab).
Media Release -
Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 12-15 March 2012.
Media Release -
Soliris(Rm) (eculizumab) Granted Marketing Authorization in Europe for Treatment of Patients with Atypical Hemolytic Uremic Syndrome (aHUS).
Media Release -
Alexion Receives CHMP Positive Opinion for Soliris(Rm) (eculizumab) in Patients with Atypical Hemolytic Uremic Syndrome (aHUS) in the European Union.
Media Release -
Alexion Submits Applications for Soliris(Rm) (Eculizumab) as a Treatment for Patients with Atypical Hemolytic Uremic Syndrome (aHUS) in the United States and European Union.
Media Release -
Researchers Present Final Data from Phase 2 Studies of Soliris(Rm) (eculizumab) in Patients with aHUS.
Media Release -
FDA Grants Priority Review for Alexion's sBLA for Soliris(Rm) (eculizumab) as a Treatment for Patients with Atypical Hemolytic Uremic Syndrome (aHUS).
Media Release -
AGNSS Recommends Soliris (eculizumab) for aHUS and Concludes Eculizumab would help save lives and improve the quality of life for children and adults with atypical haemolytic uraemic syndrome.
Media Release -
High cost of treatment for rare blood disorder needs to be clarified, says NICE in draft guidance.
Media Release -
NICE Confirms AGNSS Positive Assessment that Eculizumab (Soliris(Rm)) is a Very Effective Treatment for aHUS Patients and Produces Substantial Quality-Adjusted Life Year Gains of a Magnitude Rarely Seen for a New Drug.
Media Release -
NICE Recommends Commissioning of Eculizumab (Soliris(Rm)) for All Patients with aHUS in England.
Media Release -
NICE Issues Final Positive Recommendation for National Commissioning of Soliris(Rm) (eculizumab) for All Patients with aHUS in England.
Media Release -
NICE draft guidance recommends eculizumab (Soliris) for treating very rare life-threatening blood disorder.
Media Release -
First NICE highly specialised technologies guidance recommends eculizumab (Soliris) for treating very rare life-threatening blood disorder.
Media Release -
Alexion's Soliris(Rm) (eculizumab) Receives Marketing Approval in Japan for All Patients with aHUS.
Media Release -
Alexion's Soliris(R) (eculizumab) Receives Marketing Approval in Canada for Patients with atypical HUS.
Media Release -
An Observational, Non-Interventional, Multi-Center, Multi-National Study of Patients With Atypical Hemolytic-Uremic Syndrome (aHUS Registry)
ctiprofile -
Prospective, Single-Arm, Multicenter Study to Evaluate the Efficacy, Safety, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Eculizumab in Complement Inhibitor Treatment-Naïve Pediatric and Adult Participants With Atypical Hemolytic Uremic Syndrome (aHUS) in China
ctiprofile -
The Safety and Efficacy of Eculizumab in Japanese Patients With Atypical Hemolytic Uremic Syndrome (aHUS)
ctiprofile -
An Open-label, Multi-center Controlled Clinical Trial of Eculizumab in Adult Patients With Plasma Therapy-sensitive Atypical Hemolytic Uremic Syndrome (AHUS)
ctiprofile -
An Open-Label, Multi-Center Controlled Clinical Trial Of Eculizumab in Adolescent Patients With Plasma Therapy-Sensitive Atypical Hemolytic Uremic Syndrome (AHUS)
ctiprofile -
An Open-Label, Multi-Center Controlled Clinical Trial of Eculizumab in Adult Patients With Plasma Therapy-Resistant Atypical Hemolytic Uremic Syndrome (aHUS)
ctiprofile -
An Open-Label, Multi-Center Controlled Clinical Trial of Eculizumab in Adolescent Patients With Plasma Therapy-Resistant Atypical Hemolytic Uremic Syndrome (AHUS)
ctiprofile -
Soliris Significantly Improved Clinical Outcomes in Patients with aHUS in Pivotal Trials Published in New England Journal of Medicine.
Media Release -
Phase 2 Study of Eculizumab (Soliris(Rm)) in Patients with aHUS Resistant to Plasma Therapy Met Primary and Secondary Endpoints with High Statistical and Clinical Significance.
Media Release -
New Data Presented at the ERA-EDTA Congress Demonstrate Efficacy of Soliris(Rm) (eculizumab) in Broad Range of Patients with atypical Hemolytic Uremic Syndrome (aHUS).
Media Release -
New Data Presented at ASH Annual Meeting Enhance Clinical Knowledge of aHUS and PNH and Underscore the Effectiveness of Soliris(R) (eculizumab) Treatment.
Media Release -
Longer-term Outcome Data from the Largest Prospective Trial of Soliris(R) (eculizumab) in aHUS Underscore the Effectiveness of Ongoing Soliris Treatment.
Media Release -
Soliris(Rm) (eculizumab) Inhibits TMA and Improves Renal Function in Pediatric and Adult Patients with atypical Hemolytic Uremic Syndrome (aHUS).
Media Release -
An Open-label, Multi-center Clinical Trial of Eculizumab in Adult Patients With Atypical Hemolytic-uremic Syndrome
ctiprofile -
An Open-Label, Multi-Center Clinical Trial of Eculizumab in Pediatric Patients With Atypical Hemolytic-Uremic Syndrome
ctiprofile -
Alexion Initiates Clinical Trial of Eculizumab as a Potential Treatment for Patients with STEC-HUS in Expanded Response to EHEC Crisis in Germany.
Media Release -
Phase II, epidemiologic, open-label study of eculizumab in patients with Shiga-toxin producing E. coli haemolytic uraemic syndrome (STEC-HUS)
ctiprofile -
New Clinical Trial Data Show Substantial Improvement with Eculizumab (Soliris) in Patients with STEC-HUS.
Media Release -
Alexion Reports First Quarter 2012 Results.
Media Release -
Alexion Reports Fourth Quarter and Full Year 2011 Results.
Media Release -
Alexion Reports Second Quarter 2013 Results.
Media Release -
Alexion Reports Third Quarter 2013 Results.
Media Release -
European Commission and U.S. FDA Grant Alexion's Soliris (Rm) (eculizumab) Orphan Drug Designation for the Treatment of Atypical Hemolytic Uremic Syndrome (aHUS).
Media Release -
Alexion Reports Third Quarter 2008 Results.
Media Release -
First Clinical Experience With Soliris(R) in Treating Patients With Two Rare Complement-Mediated Diseases Presented at ASH Annual Meeting.
Media Release -
Soliris(R) (Eculizumab) Receives Marketing Authorization in Japan for the Treatment of Patients with Generalized Myasthenia Gravis (gMG).
Media Release -
Alexion Receives Positive CHMP Opinion for Soliris(R) (Eculizumab) for the Treatment of Patients with Refractory Generalized Myasthenia Gravis (gMG) in the European Union.
Media Release -
Alexion Submits Application in Japan for Soliris(R) (Eculizumab) as a Potential Treatment for Patients with Refractory Generalized Myasthenia Gravis (gMG).
Media Release -
FDA Approves Soliris(R) (Eculizumab) for the Treatment of Patients with Generalized Myasthenia Gravis (gMG).
Media Release -
FDA Accepts sBLA Filing of Soliris(Rm) (Eculizumab) as a Potential Treatment for Patients with Refractory Generalized Myasthenia Gravis (gMG).
Media Release -
Alexion Submits U.S. and EU Applications Seeking Approval of Soliris(R) (Eculizumab) as a Treatment for Patients with Refractory Generalized Myasthenia Gravis (gMG).
Media Release -
Alexion Reports Third Quarter 2016 Results.
Media Release -
European Commission Grants New Indication for Soliris(R) (Eculizumab) for the Treatment of Patients with Refractory Generalized Myasthenia Gravis (gMG).
Media Release -
Soliris approved in China for the treatment of adults with refractory generalised myasthenia gravis.
Media Release -
AstraZeneca PLC - H1 2022 results. Internet-Doc 2022;.
Available from: URL: https://www.astrazeneca.com/content/dam/az/PDF/2022/h1-2022/H1-2022-results-announcement.pdf -
Soliris approved in the EU for children and adolescents with refractory generalised myasthenia gravis (gMG).
Media Release -
Soliris recommended for approval in the EU by CHMP for children and adolescents with refractory generalised myasthenia gravis (gMG) .
Media Release -
An Open-Label, Multicenter Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Eculizumab in Pediatric Patients With Refractory Generalized Myasthenia Gravis
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Brandsema JF, Ginsberg M, Hoshino H, Mimaki M, Nagata S, Rao V, et al. A Phase 3, Open-Label, Multicenter Study To Evaluate Eculizumab In Adolescents With Refractory Generalized Myasthenia Gravis. AAN-2023 2023; abstr. S5.009.
Available from: URL: https://index.mirasmart.com/aan2023/PDFfiles/AAN2023-001926.html -
Alexion Announces Topline Results from Phase 3 REGAIN Study of Eculizumab (Soliris(R)) in Patients with Refractory Generalized Myasthenia Gravis (gMG).
Media Release -
New Data from Phase 3 REGAIN Study of Eculizumab (Soliris(R)) in Patients with Refractory Generalized Myasthenia Gravis (gMG) Presented at ICNMD Annual Congress.
Media Release -
Alexion Reports Second Quarter 2015 Results.
Media Release -
Alexion Initiates Multinational Registration Trials of Eculizumab as a Potential Treatment for Patients with Relapsing Neuromyelitis Optica (NMO) and Refractory Generalized Myasthenia Gravis (MG).
Media Release -
Alexion Reports Second Quarter 2012 Results.
Media Release -
A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate the Safety and Efficacy of Eculizumab in Subjects With Refractory Generalized Myasthenia Gravis (gMG)
ctiprofile -
Interim Analysis from Phase 3 Open-Label Extension Study Shows Sustained Benefits of Soliris(Rm) (Eculizumab) Treatment for Patients with Refractory Generalized Myasthenia Gravis.
Media Release -
A Phase III, Open-label Extension Trial of ECU-MG-301 to Evaluate the Safety and Efficacy of Eculizumab in Subjects With Refractory Generalized Myasthenia Gravis (gMG)
ctiprofile -
Nowak RJ, Muppidi S, Beydoun SR, O?Brien F, Yountz M, Howard JF. Changes in Concomitant Immunosuppressive Therapy Use During a Phase 3 Open-label Study of Eculizumab in Adults with Generalized Myasthenia Gravis: an Interim Analysis. AAN-2019 2019; abstr. P5.2-080.
Available from: URL: https://n.neurology.org/content/92/15_Supplement/P5.2-080 -
Phase 2 Study of Eculizumab (Soliris(Rm)) in Patients with Severe and Refractory Generalized Myasthenia Gravis Presented at MGFA Annual Meeting.
Media Release -
European Commission Grants Orphan Drug Designation to Soliris(R) (eculizumab) for the Treatment of Patients with Myasthenia Gravis (MG).
Media Release -
FDA Grants Orphan Drug Designation to Soliris(Rm) (eculizumab) for the Treatment of Patients with Myasthenia Gravis (MG).
Media Release -
Soliris(Rm)(eculizumab) Granted Orphan Drug Designation in Japan for the Treatment of Patients with Myasthenia Gravis.
Media Release -
Soliris approved in China for the treatment of adults with neuromyelitis optica spectrum disorder (NMOSD).
Media Release -
FDA approves first treatment for neuromyelitis optica spectrum disorder, a rare autoimmune disease of the central nervous system.
Media Release -
FDA Grants Priority Review And Accepts SBLA Of SOLIRIS(R)(Eculizumab) As A Treatment For Patients With Neuromyelitis Optica Spectrum Disorder (NMOSD).
Media Release -
Alexion Reports Fourth Quarter And Full Year 2018 Results.
Media Release -
SOLIRIS(Rm) (eculizumab) Receives Approval in Japan for the Prevention of Relapse in Patients with Neuromyelitis Optica Spectrum Disorder (NMOSD).
Media Release -
Alexion Reports First Quarter 2019 Results.
Media Release -
European Commission Approves SOLIRIS(Rm) (eculizumab) For the Treatment of Adults with Neuromyelitis Optica Spectrum Disorder (NMOSD).
Media Release -
Alexion Receives Positive CHMP Opinion for SOLIRIS(Rm) (eculizumab) for the Treatment of NMOSD.
Media Release -
Alexions Soliris (eculizumab) Receives Orphan Drug Designation for the Treatment of Neuromyelitis Optica (NMO).
Media Release -
Alexions Soliris (eculizumab) Receives Positive Opinion from the Committee for Orphan Medicinal Products for Treatment of Neuromyelitis Optica (NMO).
Media Release -
Soliris(Rm)(eculizumab) Granted Orphan Drug Designation in Japan for the Treatment of Patients with Neuromyelitis Optica.
Media Release -
Pittock S, Fujihara K, Palace J, Berthele A, Kim HJ, Guevara CO, et al. Long-term efficacy and safety of eculizumab monotherapy in AQP4+ neuromyelitis optica spectrum disorder. AAN-2021 2021; abstr. S29.004.
Available from: URL: https://index.mirasmart.com/AAN2021/PDFfiles/AAN2021-001578.html -
Wingerchuk DM, Pittock SJ, Berthele A, Fujihara K, Kim HJ, Levy M, et al. Long-term Safety and Efficacy of Eculizumab in Neuromyelitis Optica Spectrum Disorder. AAN-2020 2020; abstr. N/A.
Available from: URL: https://index.mirasmart.com/AAN2020/PDFfiles/AAN2020-001494.html -
Wingerchuk DM, Pittock SJ, Berthele A, Fujihara K, Kim HJ, Levy M, et al. Long-term safety and effectiveness of eculizumab in neuromyelitis optica spectrum disorder. ECTRIMS-2019 2019; abstr. 142.
Available from: URL: https://journals.sagepub.com/doi/full/10.1177/1352458519868070 -
Alexion Announces Successful Phase 3 PREVENT Study Of Soliris(R) (Eculizumab) In Patients With Neuromyelitis Optica Spectrum Disorder (NMOSD) .
Media Release -
Berthele A, Levy M, Wingerchuk D, Pittock S, Shang S, Kielhorn A, et al. Impact of a single relapse on disability and health-related quality of life in neuromyelitis optica spectrum disorder. ECTRIMS-2021 2021; abstr. P026.
Available from: URL: https://journals.sagepub.com/doi/full/10.1177/13524585211044667 -
Berthele A, Levy M, Johnston K, Meagan KAH, Royston M, Sabatella G, et al. The impact of relapses on quality of life in patients with neuromyelitis optica spectrum disorder: data from the phase 3 PREVENT study. AAN-2020 2020; abstr. N/A.
Available from: URL: https://index.mirasmart.com/AAN2020/PDFfiles/AAN2020-004044.html -
New England Journal of Medicine Publishes Positive Phase 3 PREVENT Data for SOLIRIS(R) (eculizumab) in Patients with Neuromyelitis Optica Spectrum Disorder (NMOSD).
Media Release -
A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Trial to Evaluate the Safety and Efficacy Of Eculizumab In Patients With Relapsing Neuromyelitis Optica (NMO)
ctiprofile -
Berthele A, Pittock SJ, Fujihara K, Kim HJ, Levy M, Palace J, et al. Impact of eculizumab on reported quality of life in patients with aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder: findings from the PREVENT study. ECTRIMS-2019 2019; abstr. P612.
Available from: URL: https://journals.sagepub.com/doi/full/10.1177/1352458519868078 -
Palace J, Pittock SJ, Berthele A, Fujihara K, Kim HJ, Levy M, et al. Impact of eculizumab on disability measures in patients with aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder: phase 3 PREVENT study. ECTRIMS-2019 2019; abstr. P1343.
Available from: URL: https://journals.sagepub.com/doi/full/10.1177/1352458519868081 -
Royston M, Kielhorn A, Tanvir I, Sabatella G. Disease outcomes in the absence of a relapse in patients with neuromyelitis optica spectrum disorder. ECTRIMS-2021 2021; abstr. P027.
Available from: URL: https://journals.sagepub.com/doi/full/10.1177/13524585211044667 -
A Phase III, Open-label, Extension Trial of ECU-NMO-301 to Evaluate the Safety and Efficacy of Eculizumab in Patients With Relapsing Neuromyelitis Optica (NMO)
ctiprofile -
A Phase 2/3 Open-Label, Single-Arm Trial to Evaluate the Safety and Activity of Eculizumab in Pediatric Patients With Relapsing Neuromyelitis Optica Spectrum Disorder
ctiprofile -
Data from Investigator-Initiated Phase 2 Study of Eculizumab (Soliris(Rm)) in Patients with Severe Relapsing Neuromyelitis Optica (NMO) Presented at the American Neurological Association (ANA) Annual Meeting.
Media Release -
Alexion Receives FDA Approval of Rhode Island Manufacturing Facility for Soliris(Rm) Supply.
Media Release -
CHMP Adopts Positive Opinion for Alexion's Soliris(TM) in Europe.
Media Release -
FDA Approves Alexion's Soliris(TM) for All Patients With PNH.
Media Release -
FDA Grants Priority Review for Soliris(TM) (eculizumab) BLA for Treatment of Paroxysmal Nocturnal Hemoglobinuria.
Media Release -
Alexion Pharmaceuticals Submits Biologics License Application for Soliris(TM) (eculizumab).
Media Release -
Alexion Reports Third Quarter 2007 Results.
Media Release -
Alexion's Soliris(TM) Granted Marketing Approval in Europe for Treatment of All Patients With PNH.
Media Release -
Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 18-21 March 2013.
Media Release -
Alexion Reports Second Quarter 2010 Results.
Media Release -
Alexion Accelerates Plans to Launch Soliris(Rm) (Eculizumab) in Japan.
Media Release -
Alexion's Soliris (Rm) (Eculizumab) Receives Marketing Approval in Japan for Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH).
Media Release -
Alexion Submits NDA in Japan for Soliris(R) (eculizumab) as a Treatment for Patients with PNH.
Media Release -
Alexion's Soliris(R) (eculizumab) Receives Marketing Approval in Canada for All Patients with PNH.
Media Release -
Soliris(TM) (Eculizumab), The First and Only Therapy For The Treatment of Patients with PNH, Is Now Available in Canada.
Media Release -
Alexion's Soliris(R) (eculizumab) Receives Marketing Approval in Australia for All Patients with PNH.
Media Release -
Open-Label, Multicenter Study to Assess the Efficacy, Safety, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Eculizumab in Complement Inhibitor Treatment Naïve Adult Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) in China.
ctiprofile -
Open Label Extension Study of Eculizumab in Patients With Transfusion Dependent PNH
ctiprofile -
Alexion Pharmaceuticals Reports Positive Phase III Results for Eculizumab From Pivotal TRIUMPH Efficacy Trial in Paroxysmal Nocturnal Hemoglobinuria Patients.
Media Release -
Randomized, Double-Blind, and Placebo-Controlled Study Using Eculizumab in Transfusion Dependent PNH Patients
ctiprofile -
Eculizumab is Well Tolerated and Demonstrates Significant Improvement During 52 Weeks of Treatment in Open-Label Phase III SHEPHERD Study in PNH Patients.
Media Release -
Alexion Pharmaceuticals Initiates Treatment in SHEPHERD, Its Second Phase III Eculizumab Trial in Paroxysmal Nocturnal Hemoglobinuria Patients.
Media Release -
Alexion Pharmaceuticals Reports Positive Interim Safety and Efficacy Results for Soliris(TM) (eculizumab) From the Open-Label Phase III SHEPHERD Safety Trial in Paroxysmal Nocturnal Hemoglobinuria Patients.
Media Release -
Safety in Hemolytic PNH Patients Treated with Eculizumab: A Multi-center Open-label Research Design Study
ctiprofile -
Soliris(R) Receives Orphan Drug Designation in Japan.
Media Release -
Alexion Reports Positive Results from AEGIS Registration Study of Soliris in Japanese Patients With PNH.
Media Release -
Alexion Commences Dosing in AEGIS Registration Study of Soliris(R) (eculizumab) in Patients with PNH in Japan.
Media Release -
An Open-Label Multi-Center Study of Eculizumab in Children and Adolescents With a Diagnosis of Paroxysmal Nocturnal Hemoglobinuria
ctiprofile -
New Research Presented at EHA Congress Shows That Soliris (RM) Significantly Reduced Hemolysis in Never-Transfused Patients with PNHSeparate Analysis of Patients with PNH and Thrombocytopenia Found Sustained Platelet Recovery Following Treatment with Soliris.
Media Release -
One Year Cumulative Results of Alexion Pharmaceuticals' Ongoing Clinical Trial in Paroxysmal Nocturnal Hemoglobinuria Presented at the British Society of Haematology Annual Meeting.
Media Release -
Alexion Pharmaceuticals Reports Two-Year Safety and Efficacy Data of Chronic Eculizumab Therapy in Patients with Paroxysmal Nocturnal Hemoglobinuria.
Media Release -
Alexion Pharmaceuticals Receives Orphan Drug Designation in the U.S. and Europe for Eculizumab in PNH.
Media Release -
Complement Regulation to Undo Systemic Harm in Preeclampsia: The CRUSH Study
ctiprofile -
Alexion Reports Second Quarter 2011 Results.
Media Release -
Alexion Provides Update on Phase 2 Clinical Trial with Eculizumab in Antibody Mediated Rejection (AMR) in Living-Donor Kidney Transplant Recipients.
Media Release -
A RANDOMIZED, OPEN-LABEL, MULTICENTER TRIAL TO DETERMINE SAFETY AND EFFICACY OF ECULIZUMAB IN THE PREVENTION OF ANTIBODY MEDIATED REJECTION (AMR) IN LIVING DONOR KIDNEY TRANSPLANT RECIPIENTS REQUIRING DESENSITIZATION THERAPY
ctiprofile -
Researchers Present New Data from Phase 2 Clinical Trial of Eculizumab (Soliris(Rm)) in Prevention of Acute Antibody-Mediated Rejection (AMR) in Sensitized Deceased-Donor Kidney Transplant Recipients.
Media Release -
Alexion Reports Fourth Quarter and Full Year 2014 Results and Provides Financial Guidance for 2015.
Media Release -
Alexion Reports Second Quarter 2014 Results.
Media Release -
Alexion Reports First Quarter 2014 Results.
Media Release -
Study Evaluating Eculizumab (Soliris(Rm)) in Preventing Antibody-Mediated Rejection (AMR) in Kidney Transplant Recipients Presented at the European Society for Organ Transplantation (ESOT) Annual Congress.
Media Release -
An Open-Label, Single-Arm, Multicenter Trial to Determine Safety and Efficacy of Eculizumab in the Prevention of Antibody Mediated Rejection (AMR) in Sensitized Recipients of a Kidney Transplant From a Deceased Donor
ctiprofile -
A phase II/III study of Eculizumab in patients for the treatment of Antibody-mediated rejection following renal transplantation
ctiprofile -
A Single Center, Open-label Study to Determine the Safety and Efficacy of a Dosing Regimen of Eculizumab Added to Conventional Treatment in the Prevention of Antibody-mediated Rejection (AMR) in ABO Blood Group Incompatible Living Donor Kidney Transplantation (ABOi LDKTx).
ctiprofile -
A Single Center, Open-label Study to Determine the Safety and Efficacy of a Dosing Regimen of Eculizumab Added to Conventional Treatment in the Prevention of Acute Humoral Rejection (AHR) in Positive Crossmatch Deceased Donor Kidney Transplantation
ctiprofile -
A Single Center, Open-label Study to Determine the Safety and Efficacy of a Dosing Regimen of Eculizumab Added to Conventional Treatment in the Prevention of Antibody-mediated Rejection (AMR) in Positive Crossmatch Living Donor Kidney Transplantation
ctiprofile -
Efficacy and Safety of Eculizumab for Treatment of Antibody-mediated Rejection Following Renal Transplantation
ctiprofile -
European Commission Grants Orphan Drug Designation to Soliris(R) (Eculizumab) for the Prevention of Graft Rejection Following Solid Organ Transplantation.
Media Release -
Researchers to Report on the Investigational Use of Alexion's Soliris(Rm) (Eculizumab) to Prevent Antibody-Mediated Rejection in High-Risk Kidney Transplant Patients.
Media Release -
Alexion Announces Top-Line Results from Phase 2/3 PROTECT Study of Eculizumab (Soliris(Rm)) for the Prevention of Delayed Graft Function (DGF) After Kidney Transplantation.
Media Release -
Alexion Reports Fourth Quarter and Full Year 2015 Results and Provides Financial Guidance for 2016.
Media Release -
Alexion Initiates Multinational Registration Trial of Eculizumab for the Prevention of Delayed Graft Function (DGF) after Kidney Transplantation.
Media Release -
FDA Grants Orphan Drug Designation to Soliris(Rm) (eculizumab) for Prevention of Delayed Graft Function (DGF) in Renal Transplant Patients.
Media Release -
A Randomized, Parallel-group, Double-blind, Placebo-controlled, Multi-center Study of Eculizumab for the Prevention of Delayed Graft Function After Kidney Transplantation in Adult Subjects at Increased Risk of Delayed Graft Function
ctiprofile -
Pilot Study of the Clinical Activity of Eculizumab for Prevention of Delayed Graft Function in Patients Undergoing Deceased Donor Kidney Transplantation
ctiprofile -
Eculizumab for Prevention of Delayed Graft Function in Deceased Donor Kidney Transplantation
ctiprofile -
European Commission Grants Orphan Drug Designation to Soliris(Rm) (Eculizumab) for Prevention of Delayed Graft Function (DGF) after Solid Organ Transplantation.
Media Release -
Alexion Reports Preliminary Results of its Phase IIb Rheumatoid Arthritis Clinical Trial.
Media Release -
Wang Y, Rollins SA, Madri JA, Matis LA. Anti-C5 monoclonal antibody therapy prevents collagen-induced arthritis and ameliorates established disease. Proc-Natl-Acad-Sci-U-S-A 1995;928955-8959.
PubMed -
Inhibition of Complement Activation (Eculizumab) in Guillain-Barre Syndrome Study
ctiprofile -
Alexion Receives Approval for Important Updates to the European Label for Soliris(Rm) (eculizumab).
Media Release -
Alexion Receives New Japanese Patent for Soliris(R)(eculizumab), Extending Patent Protection Into 2027 and Strengthening Global Patent Portfolio.
Media Release -
Alexion Receives Three New U.S. Patents for Soliris(R) (eculizumab), Extending Patent Protection Into 2027.
Media Release -
Alexion Issued Key Patent for Eculizumab in Japan.
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Alexion Provides Statement on Superior Court of Justice (STJ) Decision in Brazil Involving Soliris(Rm) (Eculizumab).
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Alexion Pharmaceuticals and PDL BioPharma Resolve Patent Dispute.
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Alexion Reports First Quarter 2020 Results.
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Alexion Reports Second Quarter 2019 Results.
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Long-Term Follow-up Study Presented at ASN 2015 Supports Effectiveness of Soliris(R) (eculizumab) in Preventing Thrombotic Microangiopathy (TMA) Events in Patients with Atypical Hemolytic Uremic Syndrome (aHUS).
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New Data Presented at ASH Annual Meeting Enhance Understanding of PNH and aHUS to Provide Optimal Care for Patients with These Life-threatening Disorders.
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New Data Highlighting Long-Term Efficacy and Safety Outcomes of PNH Patients Treated with SolirisReported at ASH Annual Meeting.
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Two-Year Data Show Long-Term Benefits of Chronic Soliris Therapy in Patients with aHUS.
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Longer-Term Data on Soliris Showed Significant and Sustained Benefits for Patients with aHUS.
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New Data Show Renal Impairment Is Strong Predictor of Early Death in Patients with PNH.
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Long-Term Efficacy, Safety and Survival Outcomes of PNH Patients Treated with Soliris(Rm) (eculizumab) Reported at ASH Annual Meeting.
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Yuzuru K, Ohyashiki K, Shichishima T, Okamoto S, Ando K, Ninomiya H, et al. Fatigue and Impaired Quality of Life in Patients with Paroxysmal Nocturnal Hemoglobinuria (Pnh) is Associated with Hemolysis, But not with Anemia. 15th-EHA-2010 2010; abstr. 1042.
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Soliris® Reduced Hemolysis, Decreased Transfusion Requirements and Improved Fatigue in Patients with PNH and Bone Marrow Insufficiency Disorders.
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Soliris(R) Reversed Thrombocytopenia in Patients with Both PNH and Pre-Existing Thrombocytopenia in Study Presented at ASH Annual Meeting.
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Long-Term Soliris (Rm) Treatment Resulted in Sustained Reduction in Hemolysis and Improved Kidney Function in Japanese Patients with PNH.
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Kelly R, Arnold L, Richards S, Hill A, vanBijnen S, Muus P, et al. Modification of the eculizumab dose to successfully manage intravascular breakthrough hemolysis in patients with paroxysmal nocturnal hemoglobinuria. 50th-ASH-2008 2008; abstr. 3441.
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Kanakura Y, Ohyashiki K, Shichishima T, Okamoto S, Ando K, Ninomiya H, et al. Safety and efficacy of the terminal complement inhibitor eculizumab in Japanese patients with paroxysmal nocturnal hemoglobinuria: AEGIS phase II clinical study results. 50th-ASH-2008 2008; abstr. 3438.
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Soliris(R) Reduced Measures of Thrombosis and Inflammation, and Decreased Indicators of Pulmonary Hypertension, in Studies of Patients with PNH.
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Soliris(R) Improved Fatigue Independent of Changes in Anemia in Patients with PNH by Controlling Hemolysis.
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Hill A, Muus P, Duhrsen U, Socie G, Risitano A, de Paz R, et al. Improvement in fatigue with eculizumab treatment of patients with paroxysmal nocturnal hemoglobinuria occurs independent of changes in anemia. Haematologica 2008;93 (Suppl. 1)359 abstr. 0903.
Available from: URL: http://online.haematologica.org -
PNH Patients With Lower Levels of Hemolysis, Mild Anemia and Minimal Transfusion Support Have Significant Disease Burden; Soliris(R) Therapy Provided Clinical Improvements in PNH Patients Regardless of Disease Severity.
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PNH Patients Treated with Soliris(TM) Experienced Dramatic Reduction in Blood Clots During Clinical Trials.
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Soliris(TM) Effective in PNH Patients With History of Aplastic Anemia and Myelodysplastic Syndromes.
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Mojcik CF, Kremer J, Bingham C, Burch F, Vitiello S, et al. Results of a phase 2B study of the humanized anti-c5 antibody eculizumab in patients with rheumatoid arthritis. Ann-Rheum-Dis 2004;63 (Suppl. 1)301.
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Alexion Reports Results of Eculizumab Trial in New England Journal of Medicine.
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Alexion Announces Results of Clinical Trial in Paroxysmal Nocturnal Hemoglobinuria Presented at the American Society of Hematology Annual Meeting.
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Alexion Reports Presentation of Membranous Nephritis Clinical Trials.
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Alexion announces completetion of phase I psoriasis pilot safety study.
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Alexion reports interim analysis of clinical safety and efficacy data from phase II rheumatoid arthritis trial.
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Alexion announces positive clinical results from phase I/II study of C5 complement inhibitor in rheumatoid arthritis patients.
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Wang Y, Hu O, Kristan J, et al. Subcutaneous administration of anti-C5 monoclonal antibody induces systemic complement inhibition and ameliorates immune complex mediated inflammatory responses. Arthritis-Rheum 1996;39 (Suppl.)245.
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Kroshus TJ, Rollins SA, Dalmasso AP, et al. Complement inhibition with an anti-C5 monoclonal antibody prevents acute cardiac tissue injury in an ex vivo model of pig-to-human xenotransplantation. Transplantation 1995;601194-1202.
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ALEXION completes phase I dermatomyositis pilot safety study.
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Salix In-Licenses Crofelemer from Napo Pharmaceuticals.
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Rollins SA, Matis LA, Springhorn JP, et al. Monoclonal antibodies directed against human C5 and C8 block complement-mediated damage of xenogeneic cells and organs. Transplantation 1995;601284-1292.
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Alexion Reports Fourth Quarter and Full Year 2019 Results.
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Soliris(R) Demonstrates Reductions in Hemolysis and Improvements in Fatigue, Overall Quality of Life and Anemia in a Broad Population of PNH Patients.
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ADDING MULTIMEDIA Alexion Receives FDA Approval of SOLIRIS(R) (eculizumab) for the Treatment of Adults with Neuromyelitis Optica Spectrum Disorder (NMOSD) who are Anti-Aquaporin-4 (AQP4) Antibody Positive.
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Alexion initiates phase II efficacy study of C5 complement inhibitor in kidney disease patients.
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Hillmen P, Hall C, Marsh JCW, Elebute M, Bombara MP, et al. Effect of eculizumab on hemolysis and transfusion requirements in patients with paroxysmal nocturnal hemoglobinuria. N-Engl-J-Med 2004;350(6):552-559.
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