Mepolizumab - GlaxoSmithKline
Alternative Names: 240563; Bosatria; Mepolizamab; Nucala; SB-240563Latest Information Update: 01 Apr 2024
At a glance
- Originator GlaxoSmithKline
- Developer GlaxoSmithKline; GSK; McMaster University; National Institute of Allergy and Infectious Diseases
- Class Anti-inflammatories; Antiallergics; Antiasthmatics; Monoclonal antibodies; Skin disorder therapies
- Mechanism of Action Interleukin 5 inhibitors
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Orphan Drug Status
Yes - Hypereosinophilic syndrome; Churg-Strauss syndrome
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 Asthma; Nasal polyps
- Registered Churg-Strauss syndrome; Hypereosinophilic syndrome
- Preregistration Chronic obstructive pulmonary disease
- Phase II Eosinophilic oesophagitis
- Discontinued Atopic dermatitis
Most Recent Events
- 23 Feb 2024 Efficacy and pharmacokinetics from the phase III long term access trial for Churg-Strauss syndrome presented at the 2024 Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI-2024)
- 23 Feb 2024 Updated efficacy data from the phase-III SYNAPSE trial in Nasal Polyps presented at the Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI-2024)
- 26 Jul 2023 Preregistration for Asthma in China (SC) prior to July 2023
Development Overview
Introduction
Mepolizumab is a humanised anti-interleukin-5 (IL-5) IgG1 monoclonal antibody that is being developed by GlaxoSmithKline (GSK), for the treatment of chronic obstructive pulmonary disease, Churg-Strauss syndrome, nasal polyps, hypereosinophilic syndrome, drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, and as an adjunctive treatment of severe eosinophilic asthma and chronic rhinosinusitis with nasal polyps. Interleukin-5 stimulates the production, activation and maturation of eosinophils. Mepolizumab binds to and inhibits IL-5 signaling, preventing IL-5 from binding to its receptor on the surface of eosinophils. This causes a sustained reduction in the numbers of circulating eosinophils, therefore may be used in conditions characterised by increased levels of eosinophils. Mepolizumab for subcutaneous injection has been launched in several countries, approved in the EU and multiple countries as an adjunctive treatment of severe eosinophilic asthma. The therapy is approved for eosinophilic granulomatosis with polyangiitis [Churg-Strauss syndrome in development table] in the US, EU, Canada and Japan, and for chronic obstructive pulmonary disease in the US. It is also approved for the treatment of hypereosinophilic syndrome, in the US and as an add-on treatment in Canada. The subcutaneous formulation is approved for bronchial asthma in Japan. Intravenous mepolizumab is approved as an add-on treatment for eosinophilic asthma in Canada. The drug is available for the treatment of nasal polyps in the US and EU, and as an add-on maintenance treatment with intranasal corticosteroids for chronic rhinosinusitis with nasal polyps in Canada. The product is approved for hypereosinophilic syndrome in the EU. The drug is under regulatory review for severe asthma in China. Clinical development in for eosinophilic asthma, Churg-Strauss syndrome, nasal polyps and chronic obstructive pulmonary disease is ongoing in several countries worldwide.
In July 2009, GSK withdrew its application for marketing approval of mepolizumab in the EU, for the treatment of hypereosinophilic syndrome.
Clinical development of intravenous mepolizumab for eosinophilic oesophagitis was conducted in the US, Australia, Canada, Switzerland and the UK. However, as at October 2020, intravenous mepolizumab was no longer present in the development pipeline and has been discontinued. Clinical development of mepolizumab was underway for atopic dermatitis in the US and Canada. However as at October 2020, the indication was no longer present in the development pipeline and drug development was been discontinued (GlaxoSmithKline pipeline, October 2020).
Key Development Milestones
Asthma
As of July 2023, GSK anticipates the regulatory approval for severe asthma in China by the end of year 2024. The regulatory application was submitted to NMPA prior to July 2023 [1] .
As of April 2023, mepolizumab is available in Argentina, Australia, Austria, Belgium, Chile, Czech Republic, Denmark, Finland, France, Germany, Hong Kong, Hungary, Ireland, Japan, Mexico, Netherlands, New Zealand, Norway, Poland, Portugal, Russia, Singapore, Spain, Sweden, Switzerland, Turkey and UK for the treatment of severe refractory eosinophilic asthma [2]
In March 2020, GlaxoSmithKline announced that mepolizumab was approved in Canada as an add-on maintenance treatment for use in adults, adolescents and children patients (aged six years and older) with severe eosinophilic asthma [3] .
In October 2019, Health Cananda approved two new methods for administering mepolizumab, an autoinjector and a pre-filled safety syringe, for patients or caregivers afflicted with severe eosinophilic asthma (SEA) or eosinophilic granulomatosis with polyangiitis (EGPA), for administration once every four weeks, following appropriate guidance from a healthcare professional [4] . Earlier, in June 2019, the US FDA had approved two new methods for administering mepolizumab, an autoinjector and a pre-filled safety syringe, for patients or caregivers afflicted with severe eosinophilic asthma (SEA) or eosinophilic granulomatosis with polyangiitis (EGPA), for administration once every four weeks, following appropriate guidance from a healthcare professional. The approval was supported by three phase III studies, NCT03099096, NCT03021304 and NCT03014674 [see below] [5] .
In December 2015, the Health Canada approved mepolizumab as an as an add-on maintenance treatment for the treatment of adult patients with uncontrolled severe eosinophilic asthma [6] .
In January 2022, US FDA has approved a 40 mg prefilled syringe of Nucala (mepolizumab) for appropriate children aged 6 to 11 years old who have severe eosinophilic asthma (SEA) [7] . In August 2019, the European Commission granted marketing authorisation for administering mepolizumab, an autoinjector and a pre-filled safety syringe, for patients or caregivers afflicted with severe eosinophilic asthma (SEA) for monthly administration. The approval was supported by three phase III studies, NCT03099096, NCT03021304 and NCT03014674 [see below] [8] . In June 2019, the EMA Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion for new self administering methods for mepolizumab, a pre-filled pen and a pre-filled safety syringe to be taken once every four weeks, for patients with severe eosinophilic asthma. The CHMP opinion was supported by positive data from three phase III studies, NCT03099096, NCT03021304 and NCT03014674 [see below] [9] .
In August 2018, European Commission granted marketing authorisation for mepolizumab (Nucala®) as an add-on treatment for severe refractory eosinophilic asthma in paediatric and adolescent patients aged six up to 17 years. The marketing authorisation was based on a partial data extrapolation approach which was agreed with the paediatrics committee (PDCO) of the EMA in which efficacy and safety data from the phase III studies conducted in patients 12 and over were extrapolated to children and was supported by the adolescent data included in the phase III severe asthma studies and a PK/PD study in children 6-11 years old with severe eosinophilic asthma [10] . Earlier in July 2018, the Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion recommending the use of mepolizumab (Nucala) as an add-on treatment for severe refractory eosinophilic asthma in paediatric patients of ages six to 17. The paediatric licence application was supported by the efficacy and safety data available in paediatric patients and its well-documented positive benefit to risk profile in adult patients. Existing data was used from adolescent participants in the mepolizumab severe asthma pivotal programme in addition to new data from children in the pharmacokinetic (PK)/ pharmacodynamic (PD) study 200363. Mepolizumab, before European approval, was made available in France as a part of an early access programme called Temporary Authorization for Utilization (ATU), for treating severe eosinophilic asthma [11] [12] .
In December 2015, the European Commission granted marketing authorisation for mepolizumab as the add-on maintenance therapy for the treatment of patients with severe eosinophilic asthma. GlaxoSmithKline received a positive opinion from the CHMP recommending marketing authorisation of the product in September 2015. The company filed MAA to the EU for the approval of mepolizumab SC for the maintenance treatment of severe refractory eosinophilic asthma in patients with a blood eosinophil count of ≥150 cells/µL at the start of treatment or 300 cells/µL in the past 12 months in November 2014 [13] [14] [15] [16] .
In December 2015, GlaxoSmithKline had launched subcutaneous mepolizumab (Nucala®) for the add-on maintenance treatment of asthma in patients of 12 years or older for use with other asthma medications [17] . In March 2016, GlaxoSmithKline reported the approval of subcutaneous mepolizumab in Australia [18] .
In November 2015, the US FDA had approved mepolizumab. Previously, in November 2014, the company had filed a BLA with the US FDA for mepolizumab as an add-on maintenance treatment for patients aged 12 years and older, with a history of exacerbations. In June 2015, the Pulmonary Allergy Drugs Advisory Committee of the US FDA recommended approval of mepolizumab in adults with severe asthma and voted that the efficacy data provided evidence of a clinically meaningful benefit in this population. The committee, however, did not recommend approval of the drug in adolescents aged 12 to 17 years and indicated that further data would be needed for approval in this population. The Prescription Drug User Fee Act (PDUFA) goal date for mepolizumab is 04 November 2015. Regulatory filings are planned in other countries in 2015 and 2016 [19] [15] [20] [21] .
In September 2019, the US FDA approved mepolizumab (Nucala®) as an add-on treatment for severe eosinophilic asthma, in patients aged six to 11 years. The approval is based on results from an open-label study which showed that the safety profile in paediatric patients aged six to 11 years was similar to the known safety profile in patients aged 12 years and older. The sBLA was filed by GlaxoSmithKline in November 2018 [22] [23] .
In March 2020, the Pharmaceuticals and Medical Devices Agency (PMDA) granted approval of mepolizumab subcutaneous injection 100 mg pediatric dosage for the treatment of bronchial asthma (for use only in patients with intractable bronchial asthma whose asthmatic responses are uncontrollable with conventional therapies) in Japan [24] .
In March 2016, mepolizumab was approved in Japan for the treatment of severe eosinophilic asthma [25] . In May 2015, GlaxoSmithKline submitted a new drug application to the Japanese Ministry of Health, Labour and Welfare for the approval of subcutaneous mepolizumab as a maintenance treatment for adults and adolescents with severe eosinophilic asthma, aged >12 years, who experience exacerbations on standard treatment [26] .
In December 2015, GlaxoSmithKline Research & Development initiated the phase IV OSMO trial to determine if there is an improvement in asthma control when directly switched to mepolizumab 100mg SC, in patients with a severe eosinophilic asthma phenotype not optimally controlled on omalizumab (204471; EudraCT2015-003697-32). The open-label, single-arm, 32-week treatment trial recruited 145 patients (aged ≥ 12 years) in the Netherlands, USA, Argentina, Belgium, Canada, France, Germany, Spain and Sweden. The trial was completed in May 2017 [27] .
In September 2022, GlaxoSmithKline completed a phase III trial that evaluated the efficacy and safety of mepolizumab as adjunctive therapy in patients with severe asthma with eosinophilic inflammation (201536; NCT03562195). The double-blind, parallel, prospective, randomised trial was initiated in August 2018 and enrolled 300 patients in China [28] . In May 2023, results from the trial were presented at 119th International Conference of the American Thoracic Society (ATS-2023) [29] .
In November 2017, GlaxoSmithKline completed a phase III study that evaluated the use of an autoinjector for the subcutaneous administration of mepolizumab, in patients with severe eosinophilic asthma (Study 204959; NCT03099096; EudraCT2016-001832-36). The study was initiated in March 2017 and enrolled 159 subjects, aged 12 years and older, in the US, Germany, Australia, Canada, Russia, the UK and Sweden [30] .
GlaxoSmithKline, in August 2017, completed a phase IIIa study that evaluated the use of a safety syringe for repeat administration of subcutaneous mepolizumab in patients with severe eosinophilic asthma (Study 205667; NCT03021304; EudraCT2016-001831-10). The open-label, single arm, repeat-dose study was initiated in February 2017, enrolled 56 patients, aged 12 years and older, in the US, the Netherlands, Canada, Russia and Sweden [31] .
In August 2017, GlaxoSmithKline completed a phase III trial which compared pharmacokinetics and safety of mepolizumab subcutaneously administered as a liquid drug product in a safety syringe or an auto-injector with the reconstituted lyophilised drug product from a vial in healthy volunteers (204958; EudraCT2016-002405-19; NCT03014674). The open-label, randomised trial initiated in January 2017, enrolled 246 volunteers in Germany, the UK and in the US. In May 2019, GlaxoSmithKline presented efficacy, adverse events, pharmacokinetics and immunogenicity data from the trial at the 115th International Conference of the American Thoracic Society (ATS-2019) [32] [33] .
University medical centre of Johannes Gutenberg University Mainz initiated the phase III MEMORY trial in October 2015 to investigate the effect of mepolizumab on airway physiology in patients with eosinophilic asthma (NCT02594332; EudraCT2015-001868-19). The randomised, double-blind, placebo-controlled trial was designed to enrol approximately 90 patients in Germany. However, the trial was prematurely ended in June 2017 [34] .
GlaxoSmithKline completed a phase III study in June 2016 that evaluated the safety and efficacy of mepolizumab as an adjunctive therapy for the treatment of patients with eosinophilic asthma (MUSCA; 200862; NCT02281318; EudraCT2014-002513-27). The study, that initiated in December 2014, evaluated the impact of the adjunctive treatment on markers of asthma control, including health-related quality of life and lung function. The randomised, double-blind, placebo-controlled, multi centre 24-week study enrolled 556 patients aged 12 years and above in the US, Argentina, Belgium, Bulgaria, Canada, Czech Republic, Estonia, France, Germany, Greece, Italy, the Netherlands, Russia, Slovakia, Spain, Ukraine, Peru, Norway and United Kingdom [35] . Data from the trial demonstrating that mepolizumab has early and sustained beneficial effects on patient-reported outcomes in patients were presented at the Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI-2017) [36] .
In August 2015, GlaxoSmithKline initiated a phase III long-term access programme for patients with severe asthma who participated in a GlaxoSmithKline-sponsored mepolizumab clinical study 200862 and 200363 (201956; NCT02543112; EudraCT2015-001152-29). Eligible patients (≥6 years of age) will initiate mepolizumab within a 6-month period following the individual patient's last scheduled visit in their preceding clinical study. For each patient benefit versus risk will be assessed throughout the study to support continued treatment with mepolizumab. The open-label trial is designed to enrol approximately 500 patients in Australia, Switzerland, Belgium, Canada, Russia, Spain, Netherlands, Argentina, Bulgaria, Czech Republic, Estonia, France, Germany, Greece, Italy, Norway, Peru, Slovakia, Ukraine, the UK, the US [37] .
In June 2020, GlaxoSmithKline reported that, the phase III COMET trial in patients with severe eosinophilic asthma met its primary endpoint (clinically significant exacerbation in Part C) and results were presented at 116th International Conference of the American Thoracic Society (ATC-2020) (201810; NCT02555371; EudraCT2015-002361-32). In July 2019, GlaxoSmithKline completed a four-part phase III trial that compared the cessation versus continuation of long-term mepolizumab 100mg SC q4w treatment, as compared with placebo, in patients with severe eosinophilic asthma The four parts of the study comprised of: Part A, a variable open-label run-in (maximum up to 132 weeks), Part B, a fixed open-label run-in (4-8 weeks), Part C, a randomised double-blind treatment period (up to 52 weeks) and in case of clinically significant asthma exacerbation, an optional open-label switch Part D (up to 52 weeks post randomisation). The trial was initiated in January 2016, and enrolled 295 patients in the US, Australia, Canada, France, Germany, Japan, South Korea, the Netherlands, Romania, Russia, Spain, Argentina, Poland, and Ukraine [38] [39] . In September 2020, efficacy results from the trial were presented at 30th Annual Congress of the European Respiratory Society (ERS-2020) [40] .
In March 2014, GlaxoSmithKline announced that the phase III MENSA trial had met its primary endpoint in comparing the efficacy of intravenous mepolizumab (75mg) and subcutaneous mepolizumab (100mg) to placebo, in adult and adolescent patients with severe and uncontrolled refractory asthma, who were receiving concurrent oral corticosteroids and have elevated blood eosinophil levels (MEA115588; NCT01691521); a reduction in the frequency of clinically significant asthma exacerbations was shown for patients receiving mepolizumab. The trial was completed in January 2014 and enrolled 576 patients aged >12 years in the US, Argentina, Australia, Belgium, Canada, Chile, Czech Republic, France, Germany, Italy, Japan, Mexico, Russia, South Korea, Spain, Ukraine and the UK [41] [16] [42] . The phase III SIRIUS trial in patients with severe treatment-refractory asthma also met its primary endpoint, demonstrating that mepolizumab produced greater reductions in oral corticosteroid use compared with placebo, while maintaining asthma control (MEA115575; NCT01691508). Mepolizumab 100mg was administered every 4 weeks by SC injection. The randomised, 20-week trial recruited 135 patients aged >12 years in the US, Australia, Canada, France, the Czech Republic, Mexico, Germany, the Netherlands, Poland and the UK [41] [16] [43] . An extension study COSMOS was completed in March 2015 for participants of the MEA115588 or MEA115575 trials (MEA115661; NCT01842607; EudraCT2012-001644-21). The open-label, trial enrolled 651 patients [44] . In October 2017, GlaxoSmithKline completed a phase III long-term safety study for mepolizumab in patients with history of life-threatening or seriously debilitating asthma who participated in the MEA115661 extension study (201312; NCT02135692). The open-label trial initiated in May 2014, enrolled 335 patients [45] . In September 2014, positive results from the phase III MENSA and SIRIUS trials were presented at the 24th Annual Congress of the European Respiratory Society (ERS-2014) [41] . In March 2016, GlaxoSmithKline presented long-term safety and efficacy data from COSMOS trial at the Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI-2015) [18] .
The phase III programme will also include safety extension trials, which will enrol mepolizumab-experienced and -naive patients [46] . Positive data from the phase III long-term extension COLUMBA trial were presented at the 114th International Conference of the American Thoracic Society in May 2018 (ATS-2018)(NCT01691859; 115666). GlaxoSmithKline, in May 2017, completed the long-term phase III COLUMBA trial, that was designed to investigate the safety in participants who had participated in MEA112997 (NCT01000506) trial. The open-label trial was initiated in September 2012, and enrolled 347 patients in the US, Argentina, Australia, Canada, Chile, France, Germany, South Korea, Poland, Romania, Russia, Ukraine and the UK [47] [48] .
In October 2016, GlaxoSmithKline released data from a meta-analysis which demonstrated that the risk of hospitalisations or emergency room visits caused by asthma attacks was halved (51% reduction p < 0.001) in severe asthma patients with an eosinophilic phenotype who received 100mg fixed dose subcutaneous injection of mepolizumab or an investigational dose of mepolizumab, compared to placebo and in addition to standard of care . The meta-analysis looked at data from 1388 patients across four randomised placebo-controlled clinical trials ranging from 24 to 52 weeks in duration, including the pivotal phase III MENSA trial (MEA115588) [49]
In April 2021, GlaxoSmithKline and National Institute of Allergy and Infectious Diseases completed the MUPPITS-2 phase II trial to evaluate the efficacy of mepolizumab, given along with standard asthma care, in children with asthma (DAIT ICAC-30; NCT03292588). The randomised trial was initiated in October 2017 and enrolled 335 patients in the US [50] .
In January 2018, GlaxoSmithKline completed a phase II study that evaluated the pharmacokinetics and pharmacodynamics of subcutaneously administered mepolizumab in children (aged 6 to 11 years) with severe eosinophilic asthma (200363; NCT02377427; EudraCT2014-002666-76; UKCRN18769; 174025; CHIL3887; P234-2014). The open-label trial was initiated in August 2015 and enrolled 28 patients in Japan, the UK, Poland and the US [51] . Results from part A of this trial showed that subcutaneous pharmacokinetics data in children of ages 6 to 11 was consistent with adults after adjustment for bodyweight and bioavailability. Data also showed that the blood eosinophil count reduction by mepolizumab in adults was predictive of eosinophil count reduction in paediatric patients. Similarity was observed in the safety profiles of mepolizumab in children and adolescents compared with that of adolescents and adults from the phase III placebo controlled severe eosinophilic asthma studies. Also, new safety concerns were not identified for paediatrics when compared with the overall adolescent and adult data [12] .
GlaxoSmithKline completed the phase II DREAM trial in March 2012 that assessed the effect of once-monthly intravenous mepolizumab on exacerbation rates in patients with severe, uncontrolled, refractory asthma (NCT01000506; MEA112997). The randomised, double-blind, placebo-controlled trial was initiated in November 2009 and enrolled 604 patients in the US, Argentina, Australia, Canada, Chile, France, Germany, South Korea, Poland, Romania, Russia, Ukraine and the UK. Results published in The Lancet in August 2012 showed that mepolizumab was associated with lower rates of clinically significant exacerbations of asthma, compared with placebo [52] .
In July 2008, GlaxoSmithKline completed a phase II trial of mepolizumab in 20 patients with symptomatic eosinophilic bronchitis with or without asthma, in Canada (NCT00292877; 9427-F2453-21C). The randomised, double-blind, placebo-controlled study evaluated the effects of intravenous mepolizumab on asthma control, airway eosinophilia and the degree to which concomitant corticosteroid treatment can be reduced. Preliminary results were reported [53] [54] .
GlaxoSmithKline completed a phase II trial in March 2012 that investigated subcutaneous mepolizumab (250, 125, 12.5mg) in the treatment of asthma (NCT01366521; 114092). The trial open-label, randomised trial was initiated in February 2011 and enrolled 65 patients in the US, Estonia, France and Germany [55] .
GlaxoSmithKline completed a phase I study in May 2012 that investigated the safety, tolerability, pharmacokinetics and pharmacodynamics of intravenously administered, single-dose mepolizumab in healthy Japanese male participants (NCT01471327) [56] .
In previous clinical studies, including trials in the EU and US, mepolizumab has shown a lack of effect on allergen-induced airway responses and inflammation despite a significant reduction in blood and sputum eosinophil levels [57] .
Chronic obstructive pulmonary disease (COPD)
GlaxoSmithKline, in September 2018, received a complete response letter (CRL) from the US FDA directing the company to submit additional clinical data in support of its supplementary biologics licence application (sBLA) for the use mepolizumab as an add-on treatment to inhaled corticosteroid-based maintenance treatment for the reduction of exacerbations in patients with chronic obstructive pulmonary disease (COPD). This treatment is supposed to be guided by blood eosinophil counts [58] .
In July 2018, the Pulmonary Allergy Drugs Advisory Committee of the US FDA, suggested that data for risk-benefit profile of mepolizumab, as an add-on to maintenance treatment for COPD, was not adequate for approval of the drug (votes: 3 for and 16 against) [59] . The Prescription Drug User Fee Act (PDUFA) target date of 7 September 2018 has been assigned. In November 2017, GlaxoSmithKline submitted a supplemental Biologics License Application (sBLA) to the US FDA. The submission was based on the results from the phase III METREX and METREO studies [see below] [60] .
Jn June 2020, GlaxoSmithKline reinitiated a phase III trial to investigate the usage of subcutaneous mepolizumab, as an add-on treatment in patients with COPD, experiencing frequent exacerbations and characterised by eosinophil levels (Study 208657; NCT04133909; EudraCT2018-001540-56). Earlier in April 2020, the trial was suspended due to COVID-19 pandemic. The randomised, double-blinded, placebo-controlled trial was initiated in October 2019 and was meant to enrol approximately 800 patients in Hungary, USA Australia, Belgium, Canada, Germany, Israel, Netherlands, New Zealand, Poland, Spin, Denmark, and in the UK [61] .
GlaxoSmithKline initiated the pivotal phase III programme (trials 117106 and 117113) for subcutaneous mepolizumab for the treatment of COPD, in April 2014 [62] .
In May 2017, the preliminary results of the pivotal phase III METREX trial demonstrated that the primary endpoint of reduction in the frequency of moderate and severe exacerbations for mepolizumab, when compared with placebo was met, in the group with higher eosinophils [63] . In January 2017, GlaxoSmithKline completed the randomised, double-blind, placebo-controlled METREX trial, to assess the efficacy of mepolizumab as an add-on therapy in patients with COPD with frequent exacerbations (Study 117106; NCT02105948; EudraCT2013-004298-28). Mepolizumab was dosed at 100mg every 4 weeks for 52 weeks, and the primary endpoint was the frequency of moderate/severe exacerbations. The trial was initiated in April 2014, as a part of the phase III programme, and enrolled 836 patients in the US, Australia, Belgium, Canada, Czech Republic, Estonia, France, Greece, Italy, Mexico, Norway, Peru, Poland, Russia, Sweden and Spain [64] [62] . In September 2017, GlaxoSmithKline released updated safety and efficacy data of the two phase III METREX and METREO (see below) trials [65] .
In May 2017, the preliminary results of the pivotal phase III METREO trial demonstrated that the primary endpoint of reduction in the frequency of moderate and severe exacerbations for mepolizumab, when compared with placebo was not met [63] . In January 2017, GlaxoSmithKline completed the randomised, double-blind, placebo-controlled METREO trial evaluating the efficacy of subcutaneous mepolizumab as an add-on therapy in patients with COPD with frequent exacerbations characterised by eosinophil level (Study 117113; NCT02105961). Mepolizumab was dosed at 100mg or 300mg every 4 weeks for 52 weeks. The trial was initiated in April 2014, as a part of the phase III programme, and enrolled 674 patients in the US, Argentina, Chile, Canada, Denmark, Germany, the Netherlands, Japan, Romania, Ukraine, South Korea,Taiwan, Slovakia and the UK [66] [62] .
In September 2015, McMaster University completed a phase III trial that investigated the efficacy of intravenous mepolizumab in patients with COPD associated with eosinophilic bronchitis (NCT01463644; RP11-3588). The double-blind, randomised trial was initiated in January 2012 and enrolled 19 patients aged 40 and 80 years in Canada [67] .
Eosinophilic granulomatosis with polyangiitis
[Churg-Strauss syndrome in development table]: In December 2017, the US FDA granted approval for mepolizumab as an add-on therapy to corticosteroids for the treatment of adult patients with eosinophilic granulomatosis with polyangiitis. The application had also received priority review status by the FDA. The Biologics License Application (sBLA) for the same was submitted in June 2017. The application was based on results from a phase III study [see below]. GlaxoSmithKline plans for regulatory filings in other countries later in 2017 and 2018 [68] [69] [70] .
Mepolizumab was granted orphan drug status by the US FDA for the treatment of Churg-Strauss syndrome in July 2011 [71] .
In October 2021, the European medicines agency (EMA) granted marketing authorisation for mepolizumab (Nucala®) for eosinophilic granulomatosis with polyangiitis (EGPA) with other medicines in patients aged 6 years and above when EGPA is relapsing-remitting or not well controlled with previous treatments [72] . In October 2020, the European Medicines Agency (EMA) accepted regulatory submissions for mepolizumab in addition to standard of care for review for the treatment of patients with eosinophilic granulomatosis with polyangiitis (EGPA) or Churg-Strauss syndrome as well as for hypereosinophilic syndrome (HES), chronic rhinosinusitis with nasal polyps (CRSwNP) [see below]. The decision of acceptance for EGPA was based on data from a phase III trial (NCT02020889) [see below] which demonstrated both accrued time in remission and proportion of patients achieving remission compared with placebo when added to standard of care [73] .
In May 2018, mepolizumab was approved in Japan as add-on maintenance treatment for patients with eosinophilic granulomatosis with polyangiitis [74] [70] .
In September 2018, Health Canada granted approval for mepolizumab as an add-on maintenance treatment for patients with eosinophilic granulomatosis with polyangiitis [75] [70] .
In September 2013, mepolizumab was granted orphan drug designation by the Pharmaceuticals and Medical Devices Agency (PMDA) Japan, for the treatment of Churg-Strauss syndrome (PMDA website, September 2013).
In February 2023, GlaxoSmithKline completed a long-term phase III trial (long term access programme) designed for patients who participated in MEA115921 study [see below] (MEA116841; 116841; EudraCT2014-003162-25; NCT03298061). The open label trial was initiated in April 2015 and enrolled 100 patients in the US, Belgium, Canada, France, Germany, Japan and the UK [76] . In February 2024, result from the trial were presented at the 2024 Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI-2024) [77]
In November 2016, GlaxoSmithKline announced that both co-primary endpoints and all secondary endpoints were met in the phase III MIRRA study of mepolizumab in patients with Churg-Strauss syndrome (115921; MEA115921; NCT02020889). [78] . In September 2016, GlaxoSmithKline completed the randomised, double-blind, placebo-controlled, phase III trial that evaluated the efficacy and safety of mepolizumab (300mg SC), given every four weeks. The 52-week study was initiated in February 2014 and enrolled 136 patients in the US, Belgium, Canada, France, Germany, Italy, Japan, Spain, and the UK [79] . The 52-week study enrolled patients with relapsing or refractory EGPA who were receiving standard of care therapy, including background corticosteroid therapy, with or without immunosuppressive therapy. The trial was conducted in collaboration with the National Institute of Allergy and Infectious Diseases. In May 2017, the company reported positive efficacy and safety results of the trial [80] . In February 2019, National Institutes of Allergic and Infectious Diseases presented data from the trial at the Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI-2019) [81] .
Hypereosinophilic syndrome (HES)
In September 2021, mepolizumab (Nucala) received approval as an add-on to standard therapy for the treatment of adults with hypereosinophilic syndrome (HES) for ≥6 months without an identifiable non-hematologic secondary cause, in Canada [82] .
In September 2020, the US FDA approved mepolizumab (Nucala) for the treatment of hypereosinophilic syndrome in adults and children aged 12 years and older, for six months or longer without another identifiable non-blood related cause of the disease. The approval based on the data from a phase III study [See below] [83] [84] . In May 2020, the US FDA had granted a priority review for GlaxoSmithKline's application seeking approval of mepolizumab in the treatment of patients with hypereosinophilic Syndrome (HES) in the US. Earlier in March 2020 GlaxoSmithKline submitted a sBLA for the same (GlaxoSmithKline pipeline, April 2020). The application is based on positive results from a pivotal phase III [see below] study that met its primary endpoint, demonstrating a statistically significant result of fewer patients experiencing a HES flare or withdrawal from the study when treated with mepolizumab, compared to placebo, when added to standard of care [70] .
In October 2021, the European medicines agency (EMA) granted marketing authorisation for mepolizumab (Nucala®) for hypereosinophilic syndrome (HES), with other medicines in adults whose disease is not well controlled with previous treatments and when the disease is linked to a blood abnormality or has no obvious cause [72] . In October 2020, the EMA accepted regulatory submissions for mepolizumab in addition to standard of care for review for the treatment of patients with HES, chronic rhinosinusitis with nasal polyps (CRSwNP) [see below] and eosinophilic granulomatosis with polyangiitis (EGPA) or Churg-Strauss syndrome [see above]. The decision of acceptance for HES was based on data from a phase III trial (NCT02836496, see below) which reported significant reduction in HES flare (worsening of symptoms or eosinophil threshold requiring an escalation in therapy) over the 32-week study period when compared with placebo when added to standard of care [73] . In July 2009, GlaxoSmithKline withdrew its MAA for mepolizumab for the treatment of HES in the EU, based on feedback from the CHMP that additional data would be required to support approval. The company stated that the withdrawal did not preclude it from filing a new application in the future [85] .
In January 2022, GlaxoSmithKline initiated the phase SPHERE III trial to investigate the efficacy and safety of mepolizumab in children and adolescents with hypereosinophilic syndrome (HES) who are receiving standard of care (SoC) therapy (EudraCT2021-000933-15; NCT04965636; 215360; P384-2020). The 52-week, open-label, single arm trial, intends to enrol approximately 25 patients in the US, Argentina and Spain [86] .
In December 2019, GlaxoSmithKline completed a phase III extension study that evaluated the long-term clinical efficacy and safety of mepolizumab, in patients with hypereosinophilic syndrome, who were enrolled in study 200622 [see below] (205203; EudraCT2017-000184-32; NCT03306043). Evaluation of the number of subjects with non-serious adverse events (AEs) as well as serious AEs and number of subjects with the presence of anti-drug antibody were the defined primary endpoints of the trial. The open-label trial, initiated in November 2017, enrolled 102 patients in the US, Argentina, Belgium, Brazil, France, Germany, Italy, Mexico, Poland, Romania, Russia, Spain and the UK. One patient was positive for anti-drug antibodies at baseline and no neutralising antibodies were detected, during the trial. Later, in May 2021, data were presented at the 117th International Conference of the American Thoracic Society (ATS-2021). Later, in June 2021, updated data were presented at the 26th Congress of the European Haematology Association (EHA-2021) [87] [88] [89] .
In November 2020 GlaxoSmithKline completed phase III compassionate use trial of mepolizumab in patients with hypereosinophilic syndrome (NCT00244686; MHE104317; EudraCT2007-000838-39). The open-label, non-randomised trial was initiated in August 2005 and enrolled 200 patients, aged 12 years and older, in the US, Canada, Australia, Belgium, France, Germany, Italy, Netherlands, Norway, Spain, Switzerland and the UK [90] .
In August 2019, GlaxoSmithKline completed the phase III trial that evaluated the efficacy and safety of mepolizumab 300mg SC injection in patients, aged ≥ 12 years, with HES (200622; NCT02836496). The randomised, double blind, placebo control trial met its primary endpoint, and was initiated in March 2017, and enrolled 108 patients in Germany, the US, Belgium, Spain, the UK, Argentina, Brazil, France, Italy, Mexico, Poland, Romania, and Russia. In November 2019, data was released by the company. Later, in May 2020, safety data was presented at the 116th International Conference of the American Thoracic Society (ATS-2020) [91] [92] [93] [94] . In February 2021, efficacy data from the trial were presented at the Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI-2021) [95] . In May 2021, efficacy data was presented at the 117th International Conference of the American Thoracic Society (ATS-2021) [96] .
A randomised, double-blind, placebo-controlled phase II trial of mepolizumab in the treatment of hypereosinophilic syndrome was completed in 2006 (NCT00086658). The 9-month trial enrolled 84 patients in the US, Canada, Australia, the EU, and Switzerland [97] . GlaxoSmithKline terminated a phase III extension trial in September 2010, which was supposed to evaluate long-term safety, efficacy and determine optimal dosing frequency of mepolizumab at the dosage of 750mg, in patients with hypereosinophilic syndrome (100901; NCT00097370). The patients enrolled in the trial were then transferred to compassionate use trial [see above NCT00244686]. The open-labelled trial initiated in September 2004, enrolled 78 patients in the US, Australia, Belgium, Canada, France, Germany and Italy [98] .
Mepolizumab received orphan drug status for first-line treatment in patients with hypereosinophilic syndrome in the US and the EU in 2004. Prior to November 2019, mepolizumab received fast track designation by the US FDA, for hypereosinophilic syndrome, in the US [92] .
Nasal polyps
As of April 2023, mepolizumab is available in US, Austria, Belgium, Chile, Czech Republic, Denmark, Finland, France, Greece, Ireland, Norway, Poland, Portugal, Spain, Sweden, Netherlands, Hungary and Germany as a treatment for patients with chronic rhinosinusitis with nasal polyps [2]
In July 2021, the US FDA approved mepolizumab (Nucala) as a treatment for patients with chronic rhinosinusitis with nasal polyps (CRSwNP), as add-on maintenance treatment in adult patients 18 years of age and older with inadequate response to nasal corticosteroids [99] . In December 2020, the US FDA accepted for review a regulatory submission made by GlaxoSmithKline seeking approval for the use of mepolizumab (Nucala) as a treatment for patients with chronic rhinosinusitis with nasal polyps (CRSwNP). The submission is based on data from the pivotal SYNAPSE study which explored the effect of mepolizumab in over 400 patients with CRSwNP (GlaxoSmithKline pipeline, January 2021) [100] .
In November 2021, GlaxoSmithKline announced that mepolizumab (NUCALA) was approved by Health Canada as an add-on maintenance treatment with intranasal corticosteroids in adult patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) inadequately controlled by intranasal corticosteroids alone, in Canada [101] .
In October 2021, the European medicines agency (EMA) granted marketing authorisation for mepolizumab (Nucala®) for severe chronic rhinosinusitis with nasal polyps (inflamed lining of the nose and sinuses with swellings in the nose) in adults [72] . In October 2020, the EMA accepted regulatory submissions for mepolizumab in addition to standard of care for review for the treatment of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) as well as for eosinophilic granulomatosis with polyangiitis (EGPA) or Churg-Strauss syndrome hypereosinophilic syndrome (HES) [see above]. The decision of acceptance for CRSwNP was based on data from a phase III SYNAPSE trial (NCT02020889) [see below] which demonstrated significant improvements in both the size of nasal polyps at the end of the 52-week study and in nasal obstruction during weeks 49-52, compared with placebo when added to standard of care, as well as reducing further surgeries up to week 52 [73] .
In April 2023, GlaxoSmithKline completed the phase III MERIT trial which was designed to assess the efficacy and safety of subcutaneous (SC) mepolizumab treatment in patients with chronic rhinosinusitis with nasal polyps (CRSwNP)/eosinophilic chronic rhinosinusitis (ECRS) (CRSwNP/ECRS) (NCT04607005; 209692). The randomised, double blind, placebo controlled, parallel group trial, initiated in February 2021, enrolled 169 patients in Japan, Russia and China [102] .
In December 2019, GlaxoSmithKline completed the pivotal phase III SYNAPSE (StudY in NAsal Polyps patientS) trial that evaluated the clinical efficacy and safety of 100mg subcutaneous mepolizumab as an add on to maintenance treatment, in adults with severe bilateral nasal polyps (NCT03085797; 205687; EudraCT2016-004255-70). The double-blind, parallel, prospective, randomised trial, 52-week trial was initiated in May 2017, and enrolled 413 patients in Argentina, Australia, Canada, Germany, Japan, the Netherlands, Romania, Russia, South Korea, Sweden, the UK and the US. In April 2020, GlaxoSmithKline released positive results for the study and declared that the study met both co-primary endpoints. In November 2020, efficacy results from the trial were presented at the Annual Scientific Meeting of the American College of Allergy, Asthma & Immunology (ACAAI-2020). In April 2021, efficacy data of 4-weekly add-on mepolizumab 100mg (SC) treatment on patients from the trial were presented at the Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI-2021). Later, in May 2021, data was presented at the 117th International Conference of the American Thoracic Society (ATS-2021). In September 2021, the data from the trial was presented at the 31st Annual Congress of the European Respiratory Society (ERS-2021) [103] [104] [105] [106] [107] [108] [109] [110] . In February 2022, GlaxoSmithKline presented phase III SYNAPSE trial data at the Annual Meeting of the American Academy of Allergy, Asthma and Immunology [111] . In February 2023, the company presented efficacy data at the Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI-2023) [112] . Similarly, in February 2024, updated efficacy results were presented at the Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI-2024) [113] [110] .
GlaxoSmithKline Research and Development plans to initiate a randomised, UK-based phase III trial to evaluate the effect of mepolizumab 100mg SC in the nasal polyp score and symptoms in patients (aged ≥ 12 years) with bilateral nasal polyps (NP) and in current need of NP surgery (UKCRN31173) [114] .
GlaxoSmithKline completed a randomised, double-blind, placebo-controlled phase II trial of mepolizumab for the treatment of severe bilateral nasal polyposis, in December 2014 (NCT01362244). The primary outcome measure was the number of patients with reduced need for surgery. The trial enrolled 110 patients in the UK, Belgium and the Netherlands [115] .
Eosinophilic oesophagitis
In December 2022, University of North Carolina in collaboration with GlaxoSmithKline, completed a phase II trial that assessed the safety and efficacy of subcutaneous administration of mepolizumab in patients with active eosinophilic oesophagitis and dysphagia predominant syndrome (NCT03656380, 18-0431). Mean change in dysphagia from baseline to 3 months post-treatment is the primary endpoint of the trial. The randomised, double blind, placebo controlled trial initiated in March 2019 enrolled 66 patients by invitation in the US [116] .
Clinical development of intravenous mepolizumab was also underway for eosinophilic oesophagitis in the US, Australia, Canada, Switzerland and the UK. However, as at October 2020, intravenous mepolizumab is no longer present in the development pipeline and has been discontinued (GlaxoSmithKline pipeline, October 2020).
In November 2008, GlaxoSmithKline completed a phase I/II trial that evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of intravenous mepolizumab in pediatric patients with eosinophilic esophagitis (MEE103219; NCT00358449). The randomised trial was initiated in September 2006 and enrolled 84 patients in the US, Canada and the UK.
Atopic dermatitis
Clinical development of mepolizumab was underway for atopic dermatitis in the US and Canada. However as at October 2020, the indication is no longer present in the development pipeline and has been discontinued (GlaxoSmithKline pipeline, October 2020).
In December 2017, GlaxoSmithKline terminated a phase II trial as the study reached pre-determined futility criteria following interim analysis and no safety concerns were noted (NCT03055195; 205050). The trial was initiated in March 2017, to investigate the efficacy and safety of mepolizumab administered subcutaneously, in patients with moderate to severe atopic dermatitis. The randomised, double-blind, placebo-controlled, parallel-group trial enrolled 34 patients in the US and Canada [117] .
Drug Properties & Chemical Synopsis
- Route of administration IV, SC
- Formulation Infusion, Injection, unspecified
- Class Anti-inflammatories, Antiallergics, Antiasthmatics, Monoclonal antibodies, Skin disorder therapies
- Target Interleukin 5
- Mechanism of Action Interleukin 5 inhibitors
-
WHO ATC code
R03D-X09 (Mepolizumab)
-
EPhMRA code
R3X (All Other Anti-Asthma and COPD Products)
- Chemical name Immunoglobulin G1, anti-(human interleukin 5) (human-mouse monoclonal SB-240563 γ1-chain), disulfide with human-mouse monoclonal SB-240563 κ-chain, dimer
- CAS Registry Number 196078-29-2
Biomarkers Sourced From Trials
| Indication | Biomarker Function | Biomarker Name | Number of Trials |
|---|---|---|---|
|
acute asthma |
Arm Group Description |
MAFD2 |
|
|
allergic asthma |
Eligibility Criteria |
Tubulin beta class IVb immunoglobulin heavy constant epsilon AGXT |
|
|
allergic asthma |
Outcome Measure |
periostin Interleukin-8 (IL-8) Interleukin-6 (IL-6) Interferon Gamma (IFNg) Interferon alpha (IFN-alpha) immunoglobulin heavy constant epsilon |
|
|
asthma |
Outcome Measure |
thymic stromal lymphopoietin tenascin C RNA binding motif protein, Y-linked, family 1, member A1 RBMY2DP proteoglycan 2, pro eosinophil major basic protein pro-melanin concentrating hormone periostin PDGFB PCNA myelin basic protein multimerin 1 Monocyte chemoattractant protein-1 (MCP-1/CCL2) mannose-binding lectin (protein C) 2,soluble L-Aspartic acid Interleukin-5 (IL-5) Interleukin-22 (IL-22) Interleukin-17 (IL-17) Interleukin-13 (IL-13) interleukin 33 interleukin 3 receptor, alpha (low affinity) Interferon Gamma (IFNg) immunoglobulinheavy constant epsilon fibulin 1 Fibroblast Growth Factor (FGF2) Fetal fibronectin Epidermal growth factor (EGF) ECP D-Urobilinogen crystallin, gamma C CRYGEP Creatinine Creatine CD31 C-reactive protein (CRP) Bilirubin ALT alpha-1 antitrypsin (SERPINA1) Alkaline phosphatase (ALPL) |
|
|
asthma |
Brief Title |
Interleukin-5 (IL-5) |
|
|
asthma |
Arm Group Description |
MAFD2 Interleukin-5 (IL-5) |
|
|
asthma |
Detailed Description |
zinc finger protein 717 tryptase delta 1 thymic stromal lymphopoietin T-cell surface antigen CD4 syndecan binding protein 2 spermidine synthase SMPD1 RNA binding motif protein, Y-linked, family 1, member A1 RBMY2DP proteoglycan 2, pro eosinophil major basic protein PCNA Obesity, susceptibility to, on chromosome 4 myelin basic protein multimerin 1 mannose-binding lectin (protein C) 2, soluble L-selectin Interleukin-5 (IL-5) interleukin 7 receptor interleukin 33 interleukin 18 receptor 1 IL1RL1 IGFBP3 IGFALS IGF1 HOP homeobox HGPRT H19, imprinted maternally expressed transcript (non-protein coding) FOXP3 Fc gamma RIIIa Fc fragment of IgG, low affinity IIIb, receptor (CD16b) eukaryotic translation initiation factor 3 subunit B Elastase, neutrophil Elastase auto-antibodies Elastase CRLF2 COPD Charcot-Leyden crystal galectin CD48 molecule CD44 alpha-1 antitrypsin (SERPINA1) ACTA2 AA1 |
|
|
asthma |
Eligibility Criteria |
Pyruvic acid immunoglobulin heavy constant epsilon FSH Estradiol-17beta 3-sulfate COPD ceroid-lipofuscinosis, neuronal 3 alpha-1 antitrypsin (SERPINA1) |
|
|
asthma |
Official Title |
Interleukin-5 (IL-5) |
|
|
asthma |
Brief Summary |
syndecan binding protein 2 SMPD1 RNA binding motif protein, Y-linked, family 1, member A1 RBMY2DP interleukin 7 receptor interleukin 18 receptor 1 IL1RL1 IGFALS IGF1 H19, imprinted maternally expressed transcript (non-protein coding) FOXP3 CRLF2 |
|
|
atopic dermatitis |
Brief Title |
Interleukin-5 (IL-5) |
|
|
atopic dermatitis |
Official Title |
Interleukin-5 (IL-5) |
|
|
bronchitis |
Brief Title |
Interleukin-5 (IL-5) |
|
|
bronchitis |
Official Title |
Interleukin-5 (IL-5) |
|
|
chronic obstructive pulmonary disease |
Brief Title |
Interleukin-5 (IL-5) COPD |
|
|
chronic obstructive pulmonary disease |
Official Title |
Interleukin-5 (IL-5) COPD |
|
|
Churg-Strauss syndrome |
Arm Group Label |
Interleukin-5 (IL-5) |
|
|
Churg-Strauss syndrome |
Outcome Measure |
pro-melanin concentrating hormone Cardiac Troponin I |
|
|
Churg-Strauss syndrome |
Brief Title |
Interleukin-5 (IL-5) |
|
|
Churg-Strauss syndrome |
Arm Group Description |
Interleukin-5 (IL-5) |
|
|
Churg-Strauss syndrome |
Eligibility Criteria |
MPO |
|
|
Churg-Strauss syndrome |
Official Title |
Interleukin-5 (IL-5) |
|
|
cough |
Eligibility Criteria |
FSH |
|
|
eosinophilia |
Arm Group Label |
Interleukin-5 (IL-5) |
|
|
eosinophilia |
Outcome Measure |
pro-melanin concentrating hormone periostin immunoglobulin heavy constant epsilon |
|
|
eosinophilia |
Brief Title |
Interleukin-5 (IL-5) |
|
|
eosinophilia |
Arm Group Description |
Interleukin-5 (IL-5) |
|
|
eosinophilia |
Detailed Description |
zinc finger protein 717 syndecan binding protein 2 spermidine synthase Obesity, susceptibility to, on chromosome 4 L-selectin interleukin 7 receptor interleukin 18 receptor 1 IL1RL1 IGFBP3 IGFALS IGF1 HOP homeobox HGPRT FOXP3 Fc gamma RIIIa Fc fragment of IgG, low affinity IIIb, receptor (CD16b) eukaryotic translation initiation factor 3 subunit B CRLF2 COPD Charcot-Leyden crystal galectin CD48 molecule CD44 alpha-1 antitrypsin (SERPINA1) |
|
|
eosinophilia |
Eligibility Criteria |
COPD alpha-1 antitrypsin (SERPINA1) |
|
|
eosinophilia |
Official Title |
Interleukin-5 (IL-5) |
|
|
eosinophilia |
Brief Summary |
syndecan binding protein 2 interleukin 7 receptor interleukin 18 receptor 1 IL1RL1 IGFALS IGF1 FOXP3 CRLF2 |
|
|
eosinophilia myalgia syndrome |
Arm Group Description |
Interleukin-5 (IL-5) |
|
|
eosinophilia myalgia syndrome |
Arm Group Label |
Interleukin-5 (IL-5) |
|
|
eosinophilia myalgia syndrome |
Brief Title |
Interleukin-5 (IL-5) |
|
|
eosinophilia myalgia syndrome |
Official Title |
Interleukin-5 (IL-5) |
|
|
eosinophilic gastroenteritis |
Arm Group Description |
Interleukin-5 (IL-5) |
|
|
eosinophilic gastroenteritis |
Arm Group Label |
Interleukin-5 (IL-5) |
|
|
eosinophilic gastroenteritis |
Brief Title |
Interleukin-5 (IL-5) |
|
|
eosinophilic gastroenteritis |
Official Title |
Interleukin-5 (IL-5) |
|
|
eosinophilic oesophagitis |
Arm Group Description |
Interleukin-5 (IL-5) |
|
|
eosinophilic oesophagitis |
Arm Group Label |
Interleukin-5 (IL-5) |
|
|
eosinophilic oesophagitis |
Brief Title |
Interleukin-5 (IL-5) |
|
|
eosinophilic oesophagitis |
Official Title |
Interleukin-5 (IL-5) |
|
|
granulomatosis with polyangiitis |
Arm Group Description |
Mesna |
|
|
hypereosinophilic syndrome |
Arm Group Label |
Interleukin-5 (IL-5) |
|
|
hypereosinophilic syndrome |
Outcome Measure |
Interleukin-5 (IL-5) |
|
|
hypereosinophilic syndrome |
Brief Title |
Interleukin-5 (IL-5) |
|
|
hypereosinophilic syndrome |
Arm Group Description |
Interleukin-5 (IL-5) |
|
|
hypereosinophilic syndrome |
Eligibility Criteria |
PDGFRB PDGFRA FIP1L1 |
|
|
hypereosinophilic syndrome |
Official Title |
Interleukin-5 (IL-5) |
|
|
nasal polyps |
Brief Title |
Interleukin-5 (IL-5) |
|
|
nasal polyps |
Official Title |
Interleukin-5 (IL-5) |
|
|
nasal polyps |
Outcome Measure |
pro-melanin concentrating hormone Interleukin-5 (IL-5) |
|
|
obstructive airway disorders |
Outcome Measure |
Interleukin-5 (IL-5) |
|
|
oesophagitis |
Outcome Measure |
Interleukin-5 (IL-5) |
|
|
sinusitis |
Brief Title |
Interleukin-5 (IL-5) |
|
|
sinusitis |
Official Title |
Interleukin-5 (IL-5) |
|
|
urticaria |
Detailed Description |
immunoglobulin heavy constant epsilon |
Biomarker
| Drug Name | Biomarker Name | Biomarker Function |
|---|---|---|
| Mepolizumab - GlaxoSmithKline | AA1 | Detailed Description |
| ACTA2 | Detailed Description | |
| AGXT | Eligibility Criteria | |
| Alkaline phosphatase (ALPL) | Outcome Measure | |
| alpha-1 antitrypsin (SERPINA1) | Detailed Description, Eligibility Criteria | |
| ALT | Outcome Measure | |
| Bilirubin | Outcome Measure | |
| C-C motif chemokine 5 (CCL5 | Detailed Description | |
| C-C motif chemokine 7 (CCL7 | Detailed Description | |
| C-C motif chemokine receptor 3 | Detailed Description, Outcome Measure | |
| C-reactive protein (CRP) | Detailed Description, Outcome Measure | |
| Cardiac Troponin I | Outcome Measure | |
| CCL26 | Outcome Measure | |
| CD31 | Outcome Measure | |
| CD44 | Detailed Description | |
| CD45 (leukocyte common antigen) | Detailed Description | |
| CD48 molecule | Detailed Description | |
| CD63 | Detailed Description, Outcome Measure | |
| ceroid-lipofuscinosis, neuronal 3 | Eligibility Criteria | |
| Charcot-Leyden crystal galectin | Detailed Description | |
| COPD | Brief Title, Detailed Description, Eligibility Criteria, Official Title | |
| Creatine | Outcome Measure | |
| Creatinine | Outcome Measure | |
| CRLF2 | Brief Summary, Detailed Description | |
| CRYGEP | Outcome Measure | |
| crystallin, gamma C | Outcome Measure | |
| D-Urobilinogen | Outcome Measure | |
| ECP | Outcome Measure | |
| Elastase | Detailed Description | |
| Elastase auto-antibodies | Detailed Description | |
| Elastase, neutrophil | Detailed Description | |
| Eotaxin (CCL11) | Detailed Description | |
| Epidermal growth factor (EGF) | Outcome Measure | |
| Estradiol-17beta 3-sulfate | Eligibility Criteria | |
| eukaryotic translation initiation factor 3 subunit B | Detailed Description | |
| Fc fragment of IgG, low affinity IIIb, receptor (CD16b) | Detailed Description | |
| Fc gamma RIIIa | Detailed Description | |
| Fetal fibronectin | Outcome Measure | |
| Fibroblast Growth Factor (FGF2) | Outcome Measure | |
| fibulin 1 | Outcome Measure | |
| FIP1L1 | Eligibility Criteria | |
| FOXP3 | Brief Summary, Detailed Description | |
| FSH | Eligibility Criteria | |
| fucosyltransferase 4 | Detailed Description | |
| H19, imprinted maternally expressed transcript (non-protein coding) | Brief Summary, Detailed Description | |
| HGPRT | Detailed Description | |
| HLA-DR | Detailed Description, Outcome Measure | |
| HOP homeobox | Detailed Description | |
| IGF1 | Brief Summary, Detailed Description | |
| IGFALS | Brief Summary, Detailed Description | |
| IGFBP3 | Detailed Description | |
| IL1RL1 | Brief Summary, Detailed Description | |
| immunoglobulin heavy constant epsilon | Detailed Description, Eligibility Criteria, Outcome Measure | |
| Interferon alpha (IFN-alpha) | Outcome Measure | |
| Interferon Gamma (IFNg) | Outcome Measure | |
| interleukin 18 receptor 1 | Brief Summary, Detailed Description | |
| interleukin 3 receptor, alpha (low affinity) | Outcome Measure | |
| interleukin 33 | Detailed Description, Outcome Measure | |
| interleukin 5 receptor subunit alpha | Arm Group Description, Arm Group Label, Detailed Description, Outcome Measure | |
| interleukin 7 receptor | Brief Summary, Detailed Description | |
| Interleukin-13 (IL-13) | Outcome Measure | |
| Interleukin-17 (IL-17) | Outcome Measure | |
| Interleukin-22 (IL-22) | Outcome Measure | |
| Interleukin-5 (IL-5) | Arm Group Description, Arm Group Label, Brief Title, Detailed Description, Official Title, Outcome Measure | |
| Interleukin-6 (IL-6) | Outcome Measure | |
| Interleukin-8 (IL-8) | Outcome Measure | |
| L-Aspartic acid | Outcome Measure | |
| L-selectin | Detailed Description | |
| MAFD2 | Arm Group Description | |
| mannose-binding lectin (protein C) 2, soluble | Detailed Description, Outcome Measure | |
| Mesna | Arm Group Description | |
| Monocyte chemoattractant protein-1 (MCP-1/CCL2) | Outcome Measure | |
| MPO | Eligibility Criteria | |
| multimerin 1 | Detailed Description, Outcome Measure | |
| myelin basic protein | Detailed Description, Outcome Measure | |
| Nitric Oxide (NO) | Detailed Description | |
| Obesity, susceptibility to, on chromosome 4 | Detailed Description | |
| PCNA | Detailed Description, Outcome Measure | |
| PDGFB | Outcome Measure | |
| PDGFRA | Eligibility Criteria | |
| PDGFRB | Eligibility Criteria | |
| periostin | Outcome Measure | |
| pro-melanin concentrating hormone | Outcome Measure | |
| prostaglandin D2 receptor | Detailed Description | |
| prostaglandin D2 receptor 2 | Detailed Description, Outcome Measure | |
| proteoglycan 2, pro eosinophil major basic protein | Detailed Description, Outcome Measure | |
| Pyruvic acid | Eligibility Criteria | |
| RBMY2DP | Brief Summary, Detailed Description, Outcome Measure | |
| RNA binding motif protein, Y-linked, family 1, member A1 | Brief Summary, Detailed Description, Outcome Measure | |
| SMPD1 | Brief Summary, Detailed Description | |
| spermidine synthase | Detailed Description | |
| syndecan binding protein 2 | Brief Summary, Detailed Description | |
| T-cell surface antigen CD4 | Detailed Description | |
| tenascin C | Outcome Measure | |
| thymic stromal lymphopoietin | Detailed Description, Outcome Measure | |
| tryptase delta 1 | Detailed Description | |
| Tubulin beta class IVb | Eligibility Criteria | |
| zinc finger protein 717 | Detailed Description |
Development Status
Summary Table
| Indication | Qualifier | Patient Segment | Phase | Countries | Route / Formulation | Developers | Event Date |
|---|---|---|---|---|---|---|---|
| Asthma | - | In children | Marketed | Japan | SC / Injection | GSK | 06 Feb 2023 |
| Asthma | - | - | Marketed | Hong Kong, New Zealand, Singapore, Turkey | SC / Injection | GSK | 06 Feb 2023 |
| Asthma | - | Adjunctive treatment, In adolescents, In adults | Marketed | Argentina, Australia, Chile, Japan, Mexico, USA | SC / Injection | GSK | 06 Feb 2023 |
| Asthma | - | Adjunctive treatment, In adolescents, In adults | Marketed | Canada | IV / Injection | GSK | 17 Nov 2021 |
| Asthma | - | Adjunctive treatment, In adolescents, In adults, In children | Marketed | Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Netherlands, Norway, Poland, Portugal, Russia, Spain, Sweden | SC / Injection | GSK | 06 Feb 2023 |
| Asthma | - | Adjunctive treatment, In adults | Marketed | Switzerland | SC / Injection | GSK | 06 Feb 2023 |
| Asthma | - | In adolescents, In adults, In children | Marketed | United Kingdom | SC / Injection | GSK | 06 Feb 2023 |
| Asthma | - | Adjunctive treatment, In adolescents, In adults | Registered | South Korea | SC / Injection | GSK | 07 Oct 2016 |
| Asthma | patients aged 6-11 years | Adjunctive treatment, In children | Registered | USA | SC / Injection | GSK | 12 Sep 2019 |
| Asthma | Age 6 to 17 years | Adjunctive treatment, In adolescents, In children | Registered | European Union, Iceland, Liechtenstein | SC / Injection | GSK | 30 Aug 2018 |
| Asthma | - | Adjunctive treatment, In adults | Registered | Canada, European Union, Iceland, Liechtenstein, Taiwan | SC / Injection | GSK | 07 Oct 2016 |
| Asthma | - | - | Preregistration | China | SC / Injection | GSK | 26 Jul 2023 |
| Asthma | Severe eosinophilic asthma patients | Adjunctive treatment, In adolescents, In adults, In the elderly | Phase III | Argentina, Poland, Romania, Ukraine | SC / Injection | GSK | 07 Jan 2016 |
| Asthma | - | Adjunctive treatment, In adolescents, In adults | Phase III | Argentina, Australia, Belgium, Chile, Czech Republic, France, Germany, Italy, Japan, Mexico, Russia, South Korea, Spain, USA, United Kingdom | IV / Injection | GSK | 20 Aug 2012 |
| Asthma | - | Adjunctive treatment, In adolescents, In adults | Phase III | Peru, Ukraine | SC / Injection | GSK | 01 Dec 2014 |
| Asthma | - | In adolescents, In adults, In children | Phase III | Argentina, Australia, Belgium, Bulgaria, Canada, Czech Republic, Estonia, France, Germany, Greece, Italy, Netherlands, Norway, Peru, Slovakia, Spain, Switzerland, Ukraine | SC / Injection | GSK | 01 Aug 2015 |
| Asthma | - | Adjunctive treatment, In adolescents, In children | Phase II | USA | SC / Injection | GSK, National Institute of Allergy and Infectious Diseases | 31 Oct 2017 |
| Atopic dermatitis | - | In adults, In the elderly | Discontinued (II) | Canada, USA | SC / unspecified | GlaxoSmithKline | 01 Oct 2020 |
| Chronic obstructive pulmonary disease | - | Adjunctive treatment | Preregistration | USA | SC / Injection | GSK | 07 Nov 2017 |
| Chronic obstructive pulmonary disease | - | In adults, In the elderly | Phase III | Canada | IV / unspecified | McMaster University | 31 Jan 2012 |
| Chronic obstructive pulmonary disease | - | Adjunctive treatment | Phase III | Argentina, Australia, Belgium, Canada, Chile, Czech Republic, Denmark, Estonia, France, Germany, Greece, Hungary, Israel, Italy, Japan, Mexico, Netherlands, New Zealand, Norway, Peru, Poland, Romania, Russia, Slovakia, South Korea, Spain, Sweden, Taiwan, Ukraine, United Kingdom | SC / Injection | GSK | 30 Oct 2019 |
| Churg-Strauss syndrome | 6 years and above | Adjunctive treatment, In adolescents, In adults, In children | Registered | European Union | SC / Injection | GSK | 13 Oct 2021 |
| Churg-Strauss syndrome | - | Adjunctive treatment | Registered | Canada, Japan, USA | SC / Injection | GSK | 10 Sep 2018 |
| Eosinophilic oesophagitis | - | In adolescents, In adults | Phase II | USA | SC / Injection | GSK | 01 Feb 2019 |
| Eosinophilic oesophagitis | - | In adolescents, In children | Discontinued (I/II) | Australia, Canada, USA, United Kingdom | IV / Infusion | GlaxoSmithKline | 01 Oct 2020 |
| Eosinophilic oesophagitis | - | - | Discontinued (I/II) | Switzerland | IV / Infusion | GlaxoSmithKline | 01 Oct 2020 |
| Hypereosinophilic syndrome | - | Adjunctive treatment, In adults | Registered | European Union | SC / Injection | GSK | 13 Oct 2021 |
| Hypereosinophilic syndrome | - | In adolescents, In adults | Registered | USA | SC / Injection | GSK | 28 Sep 2020 |
| Hypereosinophilic syndrome | Add-on to standard therapy | Adjunctive treatment | Registered | Canada | SC / Injection | GSK | 16 Sep 2021 |
| Hypereosinophilic syndrome | - | Adjunctive treatment, In adolescents, In adults, In the elderly | Phase III | Argentina, Brazil, Mexico, Russia | SC / Injection | GSK | 07 Mar 2017 |
| Hypereosinophilic syndrome | 6 Years to 17 Years (Child) | Adjunctive treatment, In adolescents, In children | Phase III | Argentina, Spain, USA | SC / Injection | GSK | 14 Jul 2022 |
| Hypereosinophilic syndrome | - | - | Phase III | Australia, Norway, Switzerland | SC / Injection | GSK | 30 Sep 2005 |
| Hypereosinophilic syndrome | MAA withdrawn | - | Preregistration Submission Withdrawal | European Union | SC / Injection | GlaxoSmithKline | 28 Feb 2010 |
| Nasal polyps | associated with chronic rhinosinusitis | Adjunctive treatment, In adults | Marketed | Austria, Belgium, Chile, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Netherlands, Norway, Poland, Portugal, Spain, Sweden, USA | SC / Injection | GSK | 06 Feb 2023 |
| Nasal polyps | chronic rhinosinusitis with nasal polyps | Adjunctive treatment | Registered | Canada | SC / Injection | GSK | 08 Nov 2021 |
| Nasal polyps | associated with chronic rhinosinusitis | Adjunctive treatment, In adults | Registered | European Union | SC / Injection | GSK | 13 Oct 2021 |
| Nasal polyps | Chronic rhinosinusitis with nasal polyps/ eosinophilic chronic rhinosinusitis | - | Phase III | China, Japan, Russia | SC / Injection | GSK | 12 Apr 2023 |
| Nasal polyps | - | Adjunctive treatment | Phase III | Argentina, Australia, Russia, South Korea | SC / Injection | GSK | 25 May 2017 |
| Nasal polyps | - | - | Phase II | Belgium, Netherlands, United Kingdom | IV / Infusion | GSK | 06 May 2009 |
Orphan Status
| Indication | Patient Segment | Country | Organisation | Event Date |
|---|---|---|---|---|
| Churg-Strauss syndrome | - | USA | GSK | 07 Jul 2011 |
| Churg-Strauss syndrome | - | Japan | GSK | 13 Sep 2013 |
| Hypereosinophilic syndrome | - | USA | GSK | 28 May 2004 |
| Hypereosinophilic syndrome | - | European Union | GSK | 29 Jul 2004 |
Commercial Information
Involved Organisations
| Organisation | Involvement | Countries |
|---|---|---|
| GlaxoSmithKline | Originator | England |
| GlaxoSmithKline | Owner | England |
| Northwestern University | Collaborator | USA |
| University of Utah | Collaborator | USA |
| McMaster University | Collaborator | Canada |
| National Institute of Allergy and Infectious Diseases | Collaborator | USA |
| Johannes Gutenberg-University Mainz | Collaborator | Germany |
Brand Names
| Brand Name | Organisations | Indications | Countries |
|---|---|---|---|
| Bosatria | GSK | Hypereosinophilic syndrome | European Union, USA |
| Nucala | GSK | Asthma, Hypereosinophilic syndrome, Nasal polyps, Churg-Strauss syndrome | USA, Greece, Japan, Canada, European Union |
Credit Suisse Market Status
| Indication | Region | Company | Phase | Expected Launch Year | Probability of Success% | Patent Expiry Year | Expected Generic Entry | Last Update |
|---|---|---|---|---|---|---|---|---|
| Asthma/nasal polyps | ex US | GSK | Marketed | 2016 | 100 | 2026 | 01 Jan 2027 | 05 Nov 2023 |
| Asthma/nasal polyps | US | GSK | Marketed | 2016 | 100 | 2027 | 01 Jan 2028 | 05 Nov 2023 |
| atopic dermatitis | Wrld (50% US) | - | Development Stopped | - | - | 2027 | - | 05 Nov 2023 |
| COPD | Wrld (50% US) | GSK | III | 2025 | 20 | 2027 | 01 Jan 2028 | 05 Nov 2023 |
Credit Suisse Financial Forecast
| Indication | Region | 2021 | 2022 | 2023 | 2024 | 2025 | 2026 | 2027 | 2028 | 2029 | 2030 | Last Update |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Asthma/nasal polyps | ex US | 624 | 672 | 731 | 776 | 776 | 776 | 776 | 776 | 776 | 621 | 05 Nov 2023 |
| Asthma/nasal polyps | US | 952 | 1092 | 1180 | 1239 | 1301 | 1366 | 1434 | 1506 | 1205 | 964 | 05 Nov 2023 |
| COPD | Wrld (50% US) | 0 | 0 | 0 | 0 | 100 | 150 | 250 | 400 | 500 | 400 | 05 Nov 2023 |
| Total | 1576 | 1764 | 1911 | 2015 | 2177 | 2292 | 2460 | 2682 | 2481 | 1985 |
Scientific Summary
-
Adverse Events
Occasional:
Abdominal pain; Arthralgia; Diarrhoea; Fatigue; Headache; Pruritus; Vomiting
Pharmacokinetic Measures
| Characterstic | Measure |
|---|---|
| Linear Kinetics | yes |
| T½beta (h) | 504 (Adult) |
Pharmacokinetics
The phase III LAP trial demonstrated that the average exposure time was 38.5(27.0) months, with a maximum of 89 months (plus 12 months for patients treated with MIRRA mepolizumab) [77] [76]
In a phase III trial conducted in healthy volunteers (n=244), pharmacokinetics profile was similar between mepolizumab, 100 mg, SC given via prefilled safety syringe (PFS) or prefilled autoinjector (AI) with reconstituted lyophilized mepolizumab. Primary as well as secondary PK parameters were comparable across the three treatment groups (90% CI: 0.80 to 1.25). Arithmetic mean (SD) for Cmax (µg/mL) for PFS, AI and lyophilised formulation were 12.55 (3.427), 12.40 (3.094) and 12.00 (3.291), respectively. Arithmetic mean (SD) for AUC0-t (µg day/mL) for PFS, AI and lyophilised formulation were 432.45 (117.841), 446.76 (101.053) and 420.29 (108.615), respectively. Arithmetic mean (SD) for AUC0-∞ (µg day/mL) for PFS, AI and lyophilised formulation were 475.47 (137.295), 494.09 (122.357) and 466.22 (119.575), respectively. Arithmetic mean (SD) for tmax (days) for PFS, AI and lyophilised formulation were 7.06 (1.9‐14.0), 7.05 (2.9‐21.0) and 7.04 (0.9‐14.1), respectively. Arithmetic mean (SD) for CL/F (L/day) for PFS, AI and lyophilised formulation were 0.233 (0.092), 0.217 (0.062) and 0.230 (0.064), respectively. Arithmetic mean (SD) for Vz/F (L) for PFS, AI and lyophilised formulation were 7.22 (2.299), 6.92 (1.823) and 7.20 (1.619), respectively. Arithmetic mean (SD) for t1/2 (days) for PFS, AI and lyophilised formulation were 22.40 (4.843), 22.90 (4.896) and 22.36 (4.173), respectively. Arithmetic mean (SD) for %AUC, extrapolated for PFS, AI and lyophilised formulation were 8.49 (4.095), 9.01 (4.264) and 8.52 (3.583), respectively. There were no difference in exposure of mepolizumab when given subcutaneously at upper arm, abdomen, or thigh [32] [33] .
Mepolizumab was administered to 12 male asthmatic patients as a 30 min intravenous infusion of 0.5, 2.5 or 10 mg/kg. The plasma clearance was 0.1 mL · h−1 · kg−1, the steady-state volume of distribution was 60 mL · kg−1 and the terminal t½ was 21 days [132] .
Adverse Events
Asthma
The most commonly reported adverse events reported in the phase III extension COSMOS study were nasal congestion (30%), upper respiratory tract infection (16%), asthma (worsening/exacerbation) (14%), and headache (14%). Total of 651 patients with severe asthma were enrolled in this study and received 100mg dose of subcutaneosuly administered mepolizumab every four weeks in addition to their standard of care respiratory medications [18] [44] .
Adverse events observed in the phase III MENSA trial of mepolizumab were similar across all treatment groups, including placebo. A total of 576 patients with severe eosinophilic asthma were randomised to receive 75mg IV or 100mg SC mepolizumab or placebo once a month for up to 8 months. The most commonly reported adverse events across all treatment groups were nasopharyngitis, headache, upper respiratory tract infection and asthma. The most common serious AE reported was asthma exacerbation, which was observed in 38 patients (6%). Systemic and local site reactions were reported in 13 (2%) and 29 (4%) patients, respectively, with no reports of mepolizumab-related anaphylaxis. Adverse events occurred at a frequency of 83% in the placebo group, 84% in the mepolizumab 75mg IV group and 78% in the 100mg SC group. The frequency of serious adverse events were 14% in the placebo group, 7% in the mepolizumab 75mg IV and 8% in the mepolizumab 100mg SC group [134] [41] [16] .
In the phase IIIb MUSCA study, the safety profile of mepolizumab was found to be consistent with its product label. Adverse events were reported in 71% (n = 193) and 75% (n = 208) in treatment and placebo arms, respectively. Serious adverse events were reported in 5% (n = 15) and 8% (n = 23) patients receiving mepolizumab and placebo, respectively [36] [119] [35] .
The most common adverse events which occurred in the phase III SIRIUS trial of mepolizumab were: headache, nasopharyngitis, bronchitis, sinusitis, fatigue and asthma. In this study, a total of 135 patients with severe asthma were randomised to receive 100mg of subcutaneously administered mepolizumab or placebo. Patients were on concurrent high dose inhaled corticosteroid and an additional controller medication. Adverse events occurred at a frequency of 92% in the placebo group and 84% in the mepolizumab treatment group. Serious adverse events occurred at a frequency of 18% in the placebo group and 1% in the mepolizumab group [41] [16] .
Long-term extended treatment with mepolizumab in the phase III COLUMBA trial in 347 patients enrolled in the phase III DREAM trial, demonstrated a safety profile consistent with the results from the earlier studies for mepolizumab. Initial improvements in lung function (mean pre-bronchodilator FEV1) gradually decreased over the study period, reflecting the general decline in lung function expected in this patient population [47] [48] .
In a phase III trial conducted in healthy volunteers (n=244), safety profile was similar between mepolizumab, 100 mg, SC given via prefilled safety syringe (PFS) or prefilled autoinjector (AI) with reconstituted lyophilized mepolizumab. The incidence of on-treatment adverse events across all three groups were 38%. On-treatment AEs reported by ≥3% participants included headache (9%), viral upper respiratory tract infection (5%), and fatigue (3%) [32] [33] .
Safety profiles in phase III COMET trial of mepolizumab was consistent with results from earlier studies of mepolizumab. Incidence of exposure-adjusted adverse events (AEs) while receiving randomized treatment was similar for mepolizumab and placebo (2740 vs 3098 AEs/1000 patient-years exposure, respectively). Mepolizumab was administered (100 mg) every 4 weeks for 52 weeks [38] [39] .
In a phase III bridging trial, treatment with mepolizumab in Chinese patient (n=300) with severe eosinophilic asthma, adverse events were consistent with the known safety profile for mepolizumab. On-treatment adverse events occurred in 135 (90.6%) patients receiving mepolizumab and 146 (96.7%) receiving placebo. The most common adverse events were infections and infestations; mepolizumab n=107 [71.8%], placebo n=112 [74.2%]). There were two deaths in those receiving placebo; none with mepolizumab. No meaningful differences between mepolizumab versus placebo were observed in laboratory parameters, electrocardiograms, or vital signs [29] [28] .
Hypereosinophilic syndrome
At the end of a 36-week placebo-controlled phase III study of mepolizumab in patients with hypereosinophilic syndrome, commonly reported adverse events included, fatigue (30% mepolizumab versus 26% placebo), pruritis (28% versus 21%), headache (23% versus 21%) and arthralgia (21% versus 17%) [123] .
In the phase III SYNAPSE study treatment with mepolizumab plus standard of care, showed safety results in consistent with the known profile of mepolizumab. The trial enrolled 413 patients with severe bilateral nasal polyps [109] [110] .
Treatment with 300mg mepolizumab, administered subcutaneously (SC) for 20 weeks, plus standard of care, was safe and generally well tolerated, in patients (n=102) with uncontrolled FIP1L1-PDGFRA-negative hypereosinophilic syndrome, who were enrolled in study 200622, in a phase III extension study. Overall, 62 (61%) patients experienced on-treatment AEs. The maximum severity was mild and moderate for 18% and 31% of patients, respectively. Treatment-related AEs were reported by 15 (15%) patients and one SAE was considered treatment-related. AEs of special interest were uncommon and no events were fatal [87] [88] [89] .
Treatment with 300mg SC injection of mepolizumab was safe and generally well tolerated, in patients (aged ≥ 12 years; n=108) with hypereosinophilic syndrome (HES), in a phase III trial. No unexpected safety signals were identified. Proportions of patients experiencing on-treatment adverse events (AEs) and serious AEs (SAEs) were similar with mepolizumab and placebo (AEs: 48/54 [89%] and 47/54 [87%]; SAEs: 10/54 [19%] and 8/54 [15%], respectively). One fatality, which was not considered related to study treatment, was reported in the mepolizumab group [91] [94] .
Eosinophilic oesophagitis
Results from a phase I/II pilot trial in 11 adults with active eosinophilic oesophagitis showed that treatment with mepolizumab (750mg, IV-infusion) was well tolerated with no clinically relevant adverse events [124] .
In the MEE103219 trial, 86% of patients reported at least one adverse event. The trial enrolled 59 patients aged 2-17 years with active eosinophilic oesophagitis, who received mepolizumab (0.55, 2.5 or 10mg/kg) once-monthly for a total of 3 infusions. The most frequent adverse events were vomiting (17%), diarrhoea (14%) and upper abdominal pain (10%). Three serious adverse events were reported (chest discomfort, oesophageal injury and food stuck in throat), but none of these was considered by the investigator to be study drug related. A total of 58 patients received all 3 infusions and 52 completed the trial [122] .
Churg-Strauss syndrome
In a 52 week pivotal phase III trial, no difference between the two treatment groups was observed in the proportion of patients experiencing on-treatment adverse events (97% versus 94%). The serious adverse events (SAEs) reported in the mepolizumab group (18%) were fewer than those in the placebo group (26%). The most frequently reported SAEs were asthma worsening (3%) exacerbation (6%). Systemic reactions were infrequent, but were in higher incidence in the mepolizumab group, when compared with placebo group. One death was reported in mepolizumab group, but was not considered to be related to study treatment by the investigator [80] . Most frequent on-treatment serious adverse events reported for mepolizumab and placebo, respectively were asthma (4%, 4%), influenza (0, 3%) and pneumonia (0, 3%). One death was reported in a patient receiving mepolizumab which was not considered by the investigator to be related to study treatment [78] [79] .
Results from the phase III trial LAP trial demonstrated that 71% completed and 3% discontinued mepolizumab due to AEs. Overall, 98% experienced AEs (43% drug-related); 38% reported serious AEs (SAEs; rate:299.5/1000 subject-years), including 6 drug-related and 1 fatal, non-drug-related (cardiac arrest). The most common SAEs were worsening of asthma(6%), worsening of EGPA(3%), and pneumonia(3%), each requiring hospitalization. Within systemic reactions AESI(4%), no anaphylaxis was reported [77] [76]
Chronic obstructive pulmonary disease
Updated results of the randomised, double-blind, pivotal phase III, 117106 (METREX) study, included the frequency of adverse events (AEs) was 80% and the frequency of serious adverse events AEs (SAEs) was 28% in the mepolizumab 100mg group. The frequency of AEs was 82% and the frequency of SAEs was 31% in the placebo group [65] [63] [64] .
Updated results of the randomised, double-blind, pivotal phase III, 117113 (METREO) study, included the frequency of adverse events (AEs) was 86% and 87% in the mepolizumab 100mg and 300mg groups, respectively and 82% in the placebo group. The frequency of serious AEs (SAEs) was 26% and 27% in the mepolizumab 100mg and 300mg groups, respectively and 30% in the placebo group [65] [63] [66] .
Pharmacodynamics
Summary
A reduction in the number of oesophageal oeosinophils was observed across all treatment groups in the MEE103219 trial in patients aged 2-17 years. The trial randomised 59 patients with active eosinophilic oesophagitis (20 eosinophils/high power field [hpf]). Patients received mepolizumab (0.55, 2.5 or 10mg/kg) once-monthly for a total of 3 infusions. Five patients (8.5%) met the primary pharmacodynamic endpoint (<5 cells/hpf at week 12), with no statistical differences among the groups. Marked reductions from baseline were observed in peak (51-74%) and mean (47-75%) oesophageal eosinophil counts. A total of 58 patients received all 3 infusions and 52 completed the trial [122] .
In the phase IV OSMO trial, treatment with mepolizumab resulted in a reduction in blood eosinophils of approximately 80% by Week 4 (vs baseline), which was sustained until Week 32. The trial was conducted in 145 patients [137] [27] .
Churg-Strauss syndrome:
Phase III:
In a pivotal phase III trial from 55 patients with relapsing or refractory EGPA, mepolizumab, 300mg q4W, in addition to standard of care therapy (glucocorticoids with or without immunosuppressants) showed significant reduction in levels of plasma eosinophil-derived neurotoxin (pEDN) at week 4 and urine eosinophil-derived neurotoxin (uEDN) at week 24 compared with samples obtained from placebo treated patients (pEDN; p < 0.0001 and uEDN; p=0.0002). Reduction in pEDN was also correlated positively with absolute eosinophil count (AEC) (R=0.57, p<0.0001 [0.33, 0.74]) and inversely with glucocorticoids dose. Moreover, the concentration of uEDN was increased with relapse of disease than the concentration reported prior initiation of treatment (GM 1420 vs. 958 ng/mg Cr; p=0.01) [81] [79] .
Twenty-four patients with atopic allergies were randomised to receive three infusions of mepolizumab or placebo over an 8-week period. Mepolizumab significantly inhibited eosinophil infiltration in skin biopsies taken at 6h and 48h after intradermal allergen challenge. It also significantly inhibited numbers of tenascin immunoreactive cells at 48h. At 6h and 48h postchallenge, there was no effect on the size of the late-phase cutaneous allergic reaction [129] .
Mepolizumab was administered to 12 male asthmatic patients as a 30 min intravenous infusion of 0.5, 2.5 or 10 mg/kg. In the majority of patients, peripheral eosinophil counts were reduced persistently and dose-dependently, relative to baseline. The maximum decrease in eosinophil counts occurred ≈ 4 days after the maximal drug concentration was achieved, and was a reduction of ≈ 85% from baseline. The IC50 value for eosinophil reduction by mepolizumab was ≈ 0.4 µg/ml [132] .
In a multicentre study, funded by GlaxoSmithKline, 24 patients with allergic asthma received either placebo or mepolizumab 750 mg by injection every 4 weeks for 12 weeks. Patients received three injections of mepolizumab altogether. Mepolizumab significantly reduced both peripheral blood eosinophil concentrations and the levels of mature and immature bone marrow eosinophils, but did not affect progenitor eosinophil cells [130] .
Twenty-four patients with atopic asthma were randomised to three infusions of mepolizumab or placebo over an 8-week period. At baseline, there was a direct correlation btween the expression of tenascin and the number of eosinophils. Mepolizumab treatment was associated with a significant reduction in the concentration of TGFβ1 in BAL fluid, the numbers of eosinophils and the expression (thickness x density) of the three extracellular matrix proteins, tenascin, lumican and procollagen III in the reticular basement membrane, suggesting eosinophils may contribute to tissue remodeling processes in asthma by regulating these proteins [128] .
In a phase II trial, three doses of mepolizumab (750 mg/dose) reduced but did not deplete eosinophils in the bronchial mucosa and bone marrow of patients (n = 24) with mild asthma. Compared with placebo, the three doses of mepolizumab significantly reduced eosinophils in the bronchial mucosa (17.91 vs 61.91; p < 0.01) and bone marrow (4.00 vs 8.00; p < 0.01) of patients [135] .
Immunogenicity
Summary
In a phase III trial conducted in healthy volunteers (n=244), anti-mepolizumab antibodies (none neutralising) were reported in 5% patients across all the group. Mepolizumab, 100 mg, SC was given via prefilled safety syringe (PFS) or prefilled autoinjector (AI) with reconstituted lyophilised mepolizumab [32] [33] .
Therapeutic Trials
Eosinophilic oesophagitis
Trends toward improvements in clinical symptoms of variable magnitude were noted in all treatment groups over weeks 9-12, in the MEE103219 trial in patients aged 2-17 years with eosinophilic oesophagitis. Patients received mepolizumab (0.55, 2.5 or 10mg/kg) once-monthly for a total of 3 infusions. Of 59 children randomised, 58 received all 3 infusions and 52 completed the trial [122] .
Results from a phase I/II pilot trial in 11 adults with active eosinophilic oesophagitis showed a convincing decrease in mean blood eosinophils following treatment with mepolizumab (750mg, iv-infusion) but not with placebo. In the oesophageal tissue, there was a major reduction in mean eosinophil count with mepolizumab from 82 to 27hpf. For placebo the reduction was from 61 to 45. The primary endpoint of peak eosinophils of <5hpf was not met. Treatment-related changes in eosinophil numbers was associated with improvement in swallowing difficulties in 2 subjects at 2 months post last infusion of mepolizumab. One subject who was treated with placebo also reported improvement [124] .
Hypereosinophilic syndrome
Mepolizumab-treated patients with hypereosinophilic syndrome had a significantly improved disease control rate compared with patients receiving placebo in a phase III international study of the agent involving 85 patients (84% versus 43%). A post-hoc analysis revealed that 47% of mepolizumab-treated patients were able to completely taper off corticosteroid treatment and remained steroid-free throughout the duration of the trial compared with 5% of patients receiving placebo (p< 0.001). Furthermore, mepolizumab treatment maintained a blood eosinophil count of ≤ 600 cells/µl for ≥ 8 consecutive weeks in 41 (95%) patients with hypereosinophilic syndrome (EHS) and was significantly higher compared with placebo (n = 19;45%) [123] [125] .
Treatment with mepolizumab 300mg, administered subcutaneously (SC) for 20 weeks, plus standard of care, showed efficacy, in patients (n=102) with uncontrolled FIP1L1-PDGFRA-negative hypereosinophilic syndrome, who were enrolled in study 200622, in a phase III extension study. The mean annualised rates of flares (95% confidence intervals) during 205203 were 0.37 (0.16, 0.86) and 0.14 (0.04, 0.49) events/year for the previous placebo and previous mepolizumab groups, respectively, versus a mean of 2.7 events for each treatment arm in the year preceding 200622. Of the 72 patients using oral corticosteroid (OCS) during weeks 0–4, 20 (28%) achieved a ≥50% reduction in daily dose during weeks 16–20. Reductions in blood eosinophil counts (BEC), observed with mepolizumab in 200622 were maintained in 205203, for the previous placebo group, the adjusted mean reduction from baseline at week 20 was 89%. Overall, there were reductions in flares, OCS use, and BEC [87] [88] [89] .
Treatment with 300mg SC injection of mepolizumab showed a significant reduction in flares, in patients (aged ≥ 12 years; n=108) with hypereosinophilic syndrome (HES), in a phase III trial. The drug showed a statistically significant result with 50% fewer patients experiencing a HES flare (worsening of symptoms or eosinophil threshold requiring an escalation in therapy) when treated with mepolizumab, compared with the placebo, when added to standard of care treatment over the 32-week study period (56% versus 28%; p = 0.002). The time to first flare was increased with mepolizumab versus placebo (p = 0.002). Risk of first HES flare over the study period was 66% lower for patients treated with mepolizumab, compared with placebo (hazard ratio 0.34; 95% CI 0.18, 0.67). There was a 66% reduction in the annualised rate of HES flares versus placebo (rate ratio 0.34; 95% CI 0.19, 0.63). Also, fatigue scores improved in mepolizumab, compared with placebo (p = 0.036) [92] . Mepolizumab showed improvement from baseline to week 32 in HES-DS score (median change: -1.19 vs -0.13, p 0.001) versus placebo. The severity of the most bothersome symptoms including breathing symptoms, skin symptoms, muscle/joint pain, nasal/sinus symptoms,, abdominal pain/ bloating, and chills/sweats, in patients with HES was improved with mepolizumab compared with placebo [95] . In patients with HES, flares were associated with symptoms linked to multiple organ systems, including skin and respiratory. For the small number of flares recorded for patients receiving mepolizumab, there were some differences in the organ systems affected, and the quantity and duration of flares was at least halved, compared with placebo. Approximately 15 flares were reported in 12/54 patients receiving mepolizumab; 35 flares were reported in 23/54 patients receiving placebo, through out the trial. Constitutional (94%, n=47/50), skin (82%, n=41/50), and respiratory (72%, n=36/50) were the most reported flare symptoms. Of the constitutional symptoms, fatigue (n=43/47) and pain (n=37/47) ranked highest. Constitutional symptoms were the most frequently reported symptoms for flares occurring in both treatment groups (mepolizumab: 100%, n=15/15; placebo: 91%, n=32/35). Nasal and respiratory flare symptoms were reported more frequently in patients receiving mepolizumab than for flares occurring in patients receiving placebo (87%, n=13/15 and 80%, n=12/15 vs 60%, n=21/35 and 69%, n=24/35, respectively). Skin and neurological flare symptoms were more common for flares occurring in patients receiving placebo (86%, n=30/35 and 60% n=21/35) than for flares occurring in patients receiving mepolizumab (73%, n=11/15 and 40%, n=6/15). Mepolizumab treatment was also associated with reduced total flare duration versus placebo (median [range] days: 10.0 [4-126] vs 26.0 [1-154]) [96] [94] .
Updated results from the phase III SYNAPSE study demonstrated at week 52, more patients receiving mepolizumab (104/206) than placebo (57/201) had NPS improvement. Those with NPS improvement had better outcomes {(mepolizumab/placebo): median (Q1, Q3) CFB PNIF 50.0[10.5,87.5]/40.0[0.0,85.0], responders: SNOT-22 91%/75%, overall VAS 83%/61%, nasal obstruction VAS 79%/60%, loss of smell VAS 49%/33%} than those without [CFB PNIF 0.0[-10.0,45.0]/0.0 [-30.0,30.0], responders, SNOT-22 54%/45%, overall VAS 44%/31%, nasal obstruction VAS 41%/27%, loss of smell VAS 23%/14%] Improved NPS was numerically associated with nasal airow in patients with CRSwNP, suggesting PNIF as a useful monitoring tool when endoscopy is not available. Although patients with NPS improvements also reported improved disease burden, NPS was less concordant with PRO than with PNIF. At Week 49–52, 79/206 (38%) patients receiving mepolizumab experienced low-symptom/symptom-free days for the overall VAS score, versus 38/201 (19%) receiving placebo (OR: 2.71; 95% CI: 1.71, 4.3; p<0.001); 145/206 (70%) patients receiving mepolizumab had symptom-reduced days versus 99/201 (49%) receiving placebo (OR: 2.44; 95% CI: 1.61, 3.70; p<0.001). From baseline to Week 49–52, 136/206 (66%) patients receiving mepolizumab experienced improvements (severe to low/moderate) in overall VAS score, versus 88/201 (44%) receiving placebo; 100/205 (48%) patients receiving mepolizumab experienced categorical shifts (severe to low/moderate) in SNOT-22 score versus 65/198 (33%) receiving placebo. Similar trends were observed at Week 21–24/Week 24 [113] [112] [103] . In the phase III SYNAPSE study, treatment with mepolizumab plus standard of care, demonstrated significant improvements in symptoms. Treatment lead to thresholds for meaningful change of -3.0 for nasal obstruction, mucus in throat, loss of smell and -2.5 for nasal discharge, facial pain, overall symptoms. At weeks 49-52, the median change from baseline in visual analogue scale (VAS) score and percentage responders (post-hoc analyses) for mepolizumab and placebo were nasal obstruction [-4.41(60%) vs -0.82(36%)]; nasal discharge [-4.51(64%) vs -0.85(40%)]; mucus in throat [-4.21(57%) vs -0.97(36%)]; loss of smell [-0.53(36%) vs 0.00(19%)]; facial pain [-3.63(58%) vs -0.68(40%)]; and overall symptoms [-4.48(64%) vs -0.90(40%)]. Loss of smell VAS showed greater improvement for patients with one prior surgery presenting a median change from baseline of -1.87 for mepolizumab, compared to placebo (-0.07). However, no differences in those with two prior surgeries were reported, vs. placebo. The results were obtained from around 407 adult patients with highly symptomatic Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) uncontrolled by previous surgery and treated with intranasal corticosteroids. At week 52, mean change from baseline total score was -29.5 (SE1.62) for mepolizumab compared with placebo -15.6 (SE 1.65), with 54% and 32% responders respectively. Odds ratio of response was 2.66 95% CI (1.75, 4.04) favouring mepolizumab. Change from baseline in all domain scores demonstrated approximately twice as large for mepolizumab compared with placebo, with similar magnitude of improvement across all domains. Later, it was reported that over the study period, 25% (52/206) of patients receiving mepolizumab and 37% (74/201) of patients receiving placebo, were treated with ≥1 course of systemic corticosteroids for nasal polyps, indicating that patients were 42% less likely to require ≥1 course of systemic corticosteroids for nasal polyps with mepolizumab treatment versus placebo (odds ratio [95% CI]: 0.58 [0.36, 0.92], P=0.020). Similarly, the probability of an initial course of systemic corticosteroids for nasal polyps was lower with mepolizumab versus placebo, from week 12 onwards. For patients with systemic corticosteroids use for nasal polyps, a similar mean (SD) number of days on systemic corticosteroids was recorded for mepolizumab (21.9 [45.8] days) and placebo (19.0 [18.5] days). However, across all patients, the mean (SD) total oral corticosteroid dose was lower with mepolizumab (109 [257] mg/year) versus placebo (181 [364] mg/year) and fewer patients received ≥200 mg/year of oral corticosteroid with mepolizumab versus placebo (19% [38/205] vs 31% [61/198]). Earlier results from the trial showed statistically significant improvements in both the size of nasal polyps (p<0.001) at week 52 and in nasal obstruction (p<0.001) during weeks 49-52, compared to placebo plus standard of care. Difference in median change from baseline for total endoscopic nasal polyps score was noted as -0.73 (95% CI: -1.11, -0.34), while the difference in median change from baseline for nasal obstruction visual analogue scale score was reported as -3.14 (95% CI: -4.09, -2.18). Statistically significant time to first actual nasal surgery up to week 52 was observed with mepolizumab plus standard of care group which showed a reduction of 57% (p=0.003) in comparison with placebo plus to standard of care group (hazard ratio [95% CI]: 0.43 [0.25, 0.76]). The trial enrolled 413 patients with severe bilateral nasal polyps. For patients with or without comorbid non-steroidal anti-inflammatory drug exacerbated respiratory disease (N-ERD) similar improvements in endoscopic NP score and reductions in surgery were observed, however improvements in obstruction VAS score were greater in patients with N-ERD. There was improvement across all endpoints with BEC ≥150 cells/μL [111] [104] [106] [105] [107] [109] [110] .
Eosinophilic dermatitis
Mepolizumab effectively treated eosinophilic dermatitis in three patients with hypereosinophilic syndrome. Three women aged 60, 62, and 82 years presented with hypereosinophilic syndrome and eosinophilic dermatitis (patients 1, 2, and 3, respectively). The patients were treated with two IV infusions of mepolizumab 750mg separated by 14 days. Within 1 day of the first mepolizumab dose, all three patients' peripheral-blood eosinophil counts and serum levels of eosinophil cationic protein were reduced. Dramatic improvements in pruritus and skin lesions were apparent by 3 days to 3 weeks after the initiation of treatment. Patient 1 remained symptom-free at 17 months' follow-up [127] .
Mepolizumab may have significant therapeutic potential for hypereosinophilic syndrome, according to US-based researchers. They administered 3 intravenous (IV) infusions of mepolizumab at a dose of 10 mg/kg (maximum of 750mg) at 4-week intervals to four patients with hypereosinophilic syndrome. Peripheral blood eosinophilic counts were lowered by mepolizumab in all patients. Throughout the study, patients experienced progressive improvements in specific symptoms, such as improvements in skin pruritus and duration, nasal congestion, exercise tolerance, and constitutional symptoms. They also had improvements in FEV1 values and objective quality of life measurements [126] .
Churg-Strauss syndrome
In a 52 week pivotal phase III trial, mepolizumab treatment in addition to standard of care therapy (glucocorticoids with or without immunosuppressants) demonstrated efficacy based on both co-primary efficacy endpoints and all secondary endpoints. The duration of remission as defined by the proportion of patients achieving at least 24 weeks duration of remission, one of five pre-defined categories of duration, was 28% (19/68) for mepolizumab and 3% (2/68) for placebo (p<0.001). The proportion of patients achieving remission at both weeks 36 and 48 of the study treatment period was 32% (22/68) for mepolizumab and 3% (2/68) for placebo (p<0.001). The patients achieving remission within the first 24 weeks and remained in remission until week 52 (19%) in mepolizumab arm, when compared with patients on placebo arm (1%) (p=0.007). Time to first relapse was significantly longer for patients on mepolizumab (p<0.001) over 52 weeks and time to first major relapse was longer for patients treated with mepolizumab, when compared with placebo (p=0.042), over 52 weeks. During weeks 48 to 52, patients treated with mepolizumab achieved significantly lower average doses of prednisolone/prednisone (44% able to taper their dose to ≤4mg/day), when compared with patients treated with placebo (7%) (p<0.001). Patients did not achieve protocol-defined remission were 47% in mepolizumab arm versus 81% in placebo arm. Approximately, half the patients treated with mepolizumab demonstrated a relapse. The rate of relapse in mepolizumab group (1.14 per year) was 50% lower than placebo group (2.27 per year), showing high morbidity rate in patients. Patients demonstrated statistically significant differences, in favour of mepolizumab, for all secondary endpoints compared to placebo [80] [78] [79] .
Asthma
Results from a randomised phase III extension COSMOS study demonstrated exacerbation rates (0.92) consistent with the pivotal MENSA study (0.91) per year at the end of the combined 84-week period. Risk of exacerbations in patients were decreased from 1.94 per year to 1.04 per year after the treatment with mepolizumab. Improvements in asthma control, as assessed by the Asthma Control Questionnaire-5 (ACQ-5) score was also observed with the improvement in the ACQ-5 score at week-4 by 0.30 points as compared to the baseline and was maintained through week 52. Post-hoc analysis evaluating durability of steriod reduction following mepolizumab treatment among the sub-set of participants from SIRIUS study that completed COSMOS demonstrated reductions in oral corticosterioid, reducing their steriod dose by 50% from a median dose of 10 mg/day to 5 mg/day. For placebo subjects from SIRIUS the median oral corticosteroid (OCS) dose achieved at the end of SIRIUS was 10 mg/day and after 52 weeks of mepolizumab treatment in COSMOS, it was reduced to 5 mg/day. For subjects who continued mepolizumab the median OCS dose achieved, at the end of both SIRIUS and COSMOS, was 2.5 mg/day. The reductions were accompanied by consistent reuctions in exacerbation rate and improvements in symptom control [136] [18] . In a post-hoc analysis combining MENSA and COSMOS studies, exacerbation rate/year remained low in patients continuing mepolizumab (Weeks 0–32: 0.91; Weeks 32–52: 0.92; Weeks 52–84: 0.92) [134] [44] .
In a phase III bridging trial, treatment with mepolizumab in Chinese patient with severe eosinophilic asthma reduced CSEs and improved SGRQ scores and pre-FEV1 values. The modified intent-to-treat population included 300 patients. At Week 52, the rate of CSEs was 65% lower (posterior probability of rate ratio <1:>0.999), and time to first CSE was longer, with mepolizumab versus placebo (p<0.001). The number of CSEs requiring hospitalization/ED visit was lower with mepolizumab versus placebo (p=0.012). There was a mean decline (improvement) in SGRQ score and an increase in pre-bronchodilator FEV1 from baseline to Week 52 in patients receiving mepolizumab versus placebo (p=0.001, p=0.006; respectively). The randomized, placebo-controlled, double-blind, parallel-group study included 300 patients [29] [28] .
Meta-analysis of data from the phase II DREAM and phase III MENSA studies showed a significant improvement in exacerbation rates in patients who received an investigational dose of mepolizumab, as compared to patients receiving placebo. A significant improvement in exacerbation rates was observed in all patient groups, stratified by baseline eosinophil levels (≥150, ≥300, ≥400, ≥500 cells/μL), and receiving mepolizumab, with the greatest improvement occurring in patients with higher levels of eosinophil. Meta-analysis demonstrated a 47% (95% CI: 38, 56) reduction in annual exacerbation rates with mepolizumab versus placebo. Clinically relevant reductions in exacerbation rate ranged from 52% to 70% for patients with a baseline eosinophil threshold of 150 cells/μL or above to 500 cells/μL or above. Phase II and phase III studies enrolled 1 192 patients: 846 patients received mepolizumab and 346 received placebo [120] .
Long-term extended treatment with mepolizumab in the phase III COLUMBA trial in 347 patients enrolled in the phase III DREAM trial, demonstrated consistent exacerbation reduction and improved asthma control. In an average of 3.5 years and a maximum of 4.5 years, the treatment resulted in 61% decrease in exacerbation rate (from 1.74 events/year at enrolment to 0.68 events/year during the treatment period; 95% confidence interval 0.60, 0.78). Consistent exacerbation rates per year over the study period (year one, 0.71, year two, 0.82, year three, 0.71) were observed. The treatment led to an improvement in asthma control (improved (ACQ5) by -0.47) from first assessment (Week 12) and maintained for over four years (until week 228). A sustained, 78% reduction in blood eosinophils (white blood cells that cause inflammation in certain people with severe asthma), from week 4 was observed till the end of the trial [47] [48] .
Administration of adjunctive mepolizumab 75mg IV or 100mg SC once a month to patients with severe eosinophilic asthma during the phase III MENSA trial resulted in a statistically significant reduction in the frequency of clinically significant exacerbations of asthma compared with placebo (primary endpoint). The percentage reductions compared with placebo were 47% (p < 0.001) for IV mepolizumab and 53% (p < 0.001) for SC mepolizumab. Both mepolizumab arms showed improvements in lung function (measured by FEV1), quality of life (measured by St George Respiratory Questionnaire) and asthma control (measured by Asthma Control Questionnaire). A subgroup analysis of time to first exacerbation demonstrated a significant reduction in the risk of exacerbations at week 16 and week 32 in patients in mepolizumab arms compared with patients in the placebo arm. In a subgroup of patients with a blood eosinophil level ≥ 500 cells/µL, 74% and 80% reduction in exacerbations was observed in patients receiving mepolizumab 75mg IV and 100mg SC, respectively. This trial included 576 patients who experienced frequent asthmatic exacerbations despite the use of high dose inhaled corticosteroids and at least one other controller medication. In another phase III trial, SIRIUS, patients with severe eosinophilic asthma who were administered mepolizumab 100mg SC once a month achieved greater reductions in maintenance oral corticosteroid dose, during weeks 20-24, compared with patients on placebo (primary endpoint; p = 0.008), while maintaining asthma control. A significant improvement in asthma control (p = 0.004) and quality of life (p = 0.019) was observed in patients in the mepolizumab arm along with a significant reduction (p = 0.001) in eosinophil count. A total of 135 patients who were on oral corticosteroids and an additional controller medication participated in this study [41] [16] .
In 362 patients with asthma, treatment with mepolizumab did not result in a significant improvement in clinical outcome measures including morning peak expiratory flow, forced expiratory volume in one second, daily β2-agonist use and symptom scores. This was despite a significant reduction in blood and sputum eosinophils. Patients received three 250mg or 750mg IV infusions of mepolizumab at monthly intervals [57] .
Data from a multicentre, randomised, double-blind, parallel, phase II trial showed that three doses of mepolizumab (750 mg/dose) had minimal effects on respiratory parameters among 24 patients with mild asthma. The three doses of mepolizumab did not significantly improve forced expiratory volume in 1 second or morning peak expiratory flow rate, compared with placebo [135] .
In a multicentre study, which was conducted by researchers from the UK and The Netherlands and supported by SmithKline Beecham (UK), 24 men with mild allergic asthma and a history of episodic wheeze and shortness of breath were randomised to receive a single IV infusion of mepolizumab 2.5 mg/kg (n = 8) or 10 mg/kg (8), or placebo. All mepolizumab recipients had substantial reductions in venous blood levels of eosinophils; the reductions were maintained for up to 16 weeks after treatment. Similarly, mepolizumab produced a dose-dependent decrease in sputum eosinophil levels which was maintained for 30 days after treatment. Blood and sputum eosinophil levels were significantly lower in mepolizumab 10 mg/kg, compared with placebo, recipients at days 9 and 30 after dosing. Neither of the mepolizumab doses had any significant effect on airway responsiveness to histamine challenge before and after allergen challenges, or on the early or maximum late asthmatic reaction, on days 8 and 29 after treatment. The researchers stated that "the striking decrease in blood and sputum eosinophil numbers after monoclonal antibody to IL-5 has potential for the treatment of asthma, allergic rhinitis, and atopic dermatitis", and suggested that the lack of effect on the late asthmatic reaction and airway hyper-responsiveness might be due to the involvement of other cell types in such responses [131] .
A substantial health impact of exacerbations was demonstrated by differences in SGRQ (St George’s Respiratory Questionnaire) score in post-hoc analysis of phase III MENSA clinical trial of mepolizumab. Mean baseline SGRQ total score among subjects with a history of ≤2 exacerbations was 42.5 compared to 49.4 for those a history of >2 exacerbations (p<0.0001). SGRQ total score for patients with a history of ≤2 exacerbations at 32 weeks was 28.5 compared to 41.5 for subjects experiencing >1 exacerbations during study treatment (p<0.0001) with changes of -15.4 and -8.0, respectively. Similar patterns were observed for SGRQ domain scores [121] [42] .
Results from the phase IIIb MUSCA study demonstrated that there was a statistically significant change in the primary endpoint of the study, that is, the St. Georges Respiratory Questionnaire (SGRQ) score. The SGRQ improved by 7.7 units from baseline vs placebo (p = 0.001) after 24 weeks. Also, at week 24, the lung function, as measured by the pre-bronchodilator FEV1, increased by 120mL (p = 0.001) more than in placebo patients. Improvements in FEV1 and SGRQ scores were sustained throughout the 24-week trial. Asthma control questionnaire showed a significant improvement in the mepolizumab treatment arm by 0.40 units (p <0.001) compared to the placebo arm. Annual rate of exacerbations and number of exacerbations requiring emergency room visits or hospitalisations reduced by 58% and 68% respectively compared with placebo [119] [35] .
Phase III COMET trial met its primary endpoint. Additional results showed that, the patients who stopped mepolizumab, 51.7% of them reported asthma worsening by week 52 versus 35.0% who continued mepolizumab. This lead to a significantly shorter time to first asthma worsening in patients who stopped the treatment. Earlier results indicated that, 46% (66/144) of patients who continued mepolizumab versus 59% (89/151) of patients who stopped mepolizumab (switched to placebo) experienced an exacerbation. Patients continuing versus stopping mepolizumab had a significantly longer time to first clinically significant exacerbation (hazard ratio [HR]: 0.62 [95% confidence interval (CI): 0.45,0.86]; P = 0.004) and time to decrease in asthma control (HR: 0.66 [0.49,0.88]; P = 0.005), with no treatment difference in the time to first exacerbation requiring ED visit/hospitalization (HR: 1.33 [0.50,3.51]; P = 0.570) following few events in both groups. Patients continuing mepolizumab maintained their eosinophil count at 40-60 cells/µL, while counts increased to 270 cells/µL by week 12 for patients who stopped mepolizumab (mepolizumab vs placebo ratio: 0.19 [0.15,0.24]; P = 0.001); this difference was maintained until week 52 (ratio: 0.16 [0.13,0.20]; P = 0.001). Mepolizumab was administered (100 mg) every 4 weeks for 52 weeks (Part C) [40] [38] [39] .
Results from a phase II study in 20 patients with eosinophilic bronchitis showed that patients who received mepolizumab were able to reduce their prednisone dose by 90% of their maximum possible compared with 55% in the placebo arm. They also had fewer eosinophilia exacerbations (n=2) and a longer median time to exacerbation (168 days) than placebo (n=8 and 101 days, respectively). Treatment with mepolizumab was accompanied by a significant decrease in sputum and blood eosinophils and improvements in asthma control. FEV1 and asthma quality of life were maintained for 8 weeks after the last infusion [53] .
Pooled analysis
Results from the primary data analysis demonstrated that patients treated with mepolizumab experienced a reduction in clinically significant exacerbations compared with both benralizumab and reslizumab across all eosinophil levels in the adjusted analysis. Mepolizumab reduced clinically significant exacerbations by 34%–45% versus benralizumab across subgroups (≥400cells/µL- 45%, ≥300cells/µL-39%, ≥150cells/µL-34%, p < 0.05). Mepolizumab reduced clinically significant exacerbations by 45% versus reslizumab in the ≥400cells/µL subgroup (p < 0.007). Asthma control was significantly improved with mepolizumab versus benralizumab (all subgroups: p<0.05), and versus reslizumab in the ≥400 cells/μL subgroup (p=0.004). Benralizumab significantly improved lung function versus reslizumab in the ≥400 cells/μL subgroup (p=0.025).
In a phase III trial conducted in healthy volunteers (n=244), mepolizumab 100 mg, SC showed similar reduction in oeosinophils when given via prefilled safety syringe (PFS) or prefilled autoinjector (AI) with reconstituted lyophilised mepolizumab [32] [33] .
The preliminary results of the pivotal phase III, 117113 trial demonstrated the reduction in the frequency of moderate and severe exacerbations for mepolizumab 100mg or 300mg, when compared with placebo, was not statistically significant (20% for 100mg, p=0.068; 14% for 300mg, p=0.140 after multiplicity adjustment). The randomised, double-blind, METREO trial assessed mepolizumab subcutaneous injection in 674 patients with chronic obstructive pulmonary disease [65] [63] [66] .
Chronic obstructive pulmonary disease
The preliminary results of the pivotal phase III, 117106 trial demonstrated a statistically significant reduction in the frequency of moderate and severe exacerbations for mepolizumab 100mg, when compared with placebo, in the group with higher eosinophils (18%, p=0.036 after multiplicity adjustment). The randomised, double-blind, METREX trial assessed mepolizumab subcutaneous injection in 836 patients with chronic obstructive pulmonary disease [65] [63] [64] .
Future Events
| Expected Date | Event Type | Description | Updated |
|---|---|---|---|
| 31 Dec 2024 | Regulatory Status | GSK anticipates regulatory decision from China's NMPA for Asthma in 2H 2024 (3809807) | 02 Aug 2023 |
| 31 Dec 2024 | Regulatory Status | GSK anticipates regulatory decision from Japan's MHLW for Nasal polyps in 2H 2024 (3809807) | 02 Aug 2023 |
| 31 Dec 2024 | Regulatory Status | GSK announces intention to submit regulatory application to US FDA for Chronic obstructive pulmonary disease in 2H 2024 (3809807) | 02 Aug 2023 |
| 31 Dec 2023 | Regulatory Status | GSK anticipates regulatory submission for Nasal polyps in China in second half of 2023 (3809807) | 01 Aug 2023 |
| 31 Dec 2023 | Regulatory Status | GSK anticipates regulatory submission for Nasal polyps in Japan in second half of 2023 (3809807) | 01 Aug 2023 |
| 31 Jan 2022 | Trial Update | GlaxoSmithKline plans the phase III SPHERE trial for Hypereosinophilic syndrome (In children, In adolescents) in January 2022 (NCT04965636) | 16 Feb 2022 |
| 30 Nov 2021 | Trial Update | GlaxoSmithKline plans an investigator-initiated pilot clinical trial for DRESS syndrome in Australia (SC) in November 2021 (ACTRN12621001333808 ) | 03 Jan 2022 |
| 28 Jan 2021 | Trial Update | GlaxoSmithKline plans the phase III MERIT trial in Nasal polyps and Rhinosinusitis in January 2021 (SC, Injection) (NCT04607005) (700329340) | 07 Jun 2021 |
| 31 Dec 2020 | Regulatory Status | GlaxoSmithKline anticipates regulatory submissions for Nasal polyps in second half of 2020 [118] | 06 Jan 2021 |
| 31 Aug 2019 | Regulatory Status | GlaxoSmithKline expects the first European launches of the two new methods for administering mepolizumab, an autoinjector and a pre-filled safety syringe for Asthma in August 2019 [8] | 07 Aug 2019 |
| 07 Sep 2018 | Regulatory Status | FDA assigns PDUFA action date of 07 /09/2018 for mepolizumab for Chronic obstructive pulmonary disease (Adjunctive-treatment) [59] | 11 Nov 2021 |
| 17 Aug 2018 | Trial Update | GlaxoSmithKline plans a phase III trial for Asthma in August 2018 (700296943), (NCT03562195) | 05 Oct 2018 |
| 31 Dec 2017 | Regulatory Status | GlaxoSmithKline plans to file an regulatory application for Chronic obstructive pulmonary disease in 2017 [65] | 08 Nov 2017 |
| 31 Jul 2017 | Trial Update | GlaxoSmithKline plans a phase III trial for Hypereosinophilic syndrome (In adolescents, In adults, In the elderly) in Argentina, Belgium, Brazil, Mexico, Russia and USA (EudraCT2017-000184-32) | 15 Dec 2017 |
| 31 May 2017 | Trial Update | GlaxoSmithKline plans a phase III trial for Nasal polyps (NCT03085797) | 25 Jul 2017 |
| 05 May 2017 | Trial Update | GlaxoSmithKline plans a phase III trial for Asthma (NCT03099096) | 02 Jun 2017 |
| 30 Apr 2017 | Trial Update | GlaxoSmithKline plans a phase II trial for Atopic dermatitis in USA (NCT03055195) | 11 Nov 2021 |
Development History
| Event Date | Update Type | Comment |
|---|---|---|
| 23 Feb 2024 | Scientific Update | Efficacy and pharmacokinetics from the phase III long term access trial for Churg-Strauss syndrome presented at the 2024 Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI-2024) [77] Updated 01 Apr 2024 |
| 23 Feb 2024 | Scientific Update | Updated efficacy data from the phase-III SYNAPSE trial in Nasal Polyps presented at the Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI-2024) [113] Updated 01 Apr 2024 |
| 05 Nov 2023 | Financial Update | Credit Suisse financial data update Updated 05 Nov 2023 |
| 26 Jul 2023 | Phase Change - Preregistration | Preregistration for Asthma in China (SC) prior to July 2023 [1] Updated 02 Aug 2023 |
| 26 Jul 2023 | Regulatory Status | GSK announces intention to submit regulatory application to US FDA for Chronic obstructive pulmonary disease in 2H 2024 [1] Updated 02 Aug 2023 |
| 26 Jul 2023 | Regulatory Status | GSK anticipates regulatory decision from China's NMPA for Asthma in 2H 2024 [1] Updated 02 Aug 2023 |
| 26 Jul 2023 | Regulatory Status | GSK anticipates regulatory decision from Japan's MHLW for Nasal polyps in 2H 2024 [1] Updated 02 Aug 2023 |
| 26 Jul 2023 | Regulatory Status | GSK anticipates regulatory submission for Nasal polyps in China in second half of 2023 [1] Updated 01 Aug 2023 |
| 26 Jul 2023 | Regulatory Status | GSK anticipates regulatory submission for Nasal polyps in Japan in second half of 2023 [1] Updated 01 Aug 2023 |
| 19 May 2023 | Scientific Update | Efficacy and adverse event data from a phase III trial in Asthma presented at the119th International Conference of the American Thoracic Society (ATS-2023) [29] Updated 08 Jul 2023 |
| 12 Apr 2023 | Trial Update | GlaxoSmithKline completes a phase III MERIT trial in Nasal polyps in China, Russia, Japan (SC) (NCT04607005) Updated 26 Feb 2024 |
| 24 Feb 2023 | Scientific Update | Updated efficacy data from a phase III SYNAPSE trial in Nasal Polyps presented at the Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI-2023) [112] Updated 19 Apr 2023 |
| 16 Feb 2023 | Trial Update | GlaxoSmithKline completes a phase III long term access trial for Churg-Strauss syndrome (Adjunctive treatment) in the USA, Belgium, Canada, France, Germany, Japan and the United Kingdom (NCT03298061) (EudraCT2014-003162-25) Updated 31 Jan 2024 |
| 06 Feb 2023 | Phase Change - Marketed | Launched for Asthma (Adjunctive treatment, In adolescents, In adults) in Argentina (SC) prior to February 2023 [2] Updated 06 Jun 2023 |
| 06 Feb 2023 | Phase Change - Marketed | Launched for Asthma (Adjunctive treatment, In adolescents, In adults) in Australia (SC) prior to February 2023 [2] Updated 06 Jun 2023 |
| 06 Feb 2023 | Phase Change - Marketed | Launched for Asthma (Adjunctive treatment, In adolescents, In adults) in Chile (SC) prior to February 2023 [2] Updated 06 Jun 2023 |
| 06 Feb 2023 | Phase Change - Marketed | Launched for Asthma (Adjunctive treatment, In adolescents, In adults) in Japan (SC) prior to February 2023 [2] Updated 06 Jun 2023 |
| 06 Feb 2023 | Phase Change - Marketed | Launched for Asthma (Adjunctive treatment, In adolescents, In adults) in Mexico (SC) prior to February 2023 [2] Updated 06 Jun 2023 |
| 06 Feb 2023 | Phase Change - Marketed | Launched for Asthma (Adjunctive treatment, In adolescents, In adults, In children) in Russia (SC) prior to February 2023 [2] Updated 06 Jun 2023 |
| 06 Feb 2023 | Phase Change - Marketed | Launched for Asthma (Adjunctive treatment, In adolescents, In children, In adults) in Poland, Belgium, Germany, Denmark, Hungary, Austria, Ireland, France, Netherlands, Spain, Czech Republic, Sweden, Portugal, Finland, Norway (SC) prior to February 2023 [2] Updated 06 Jun 2023 |
| 06 Feb 2023 | Phase Change - Marketed | Launched for Asthma (Adjunctive treatment, In adults) in Switzerland (SC) prior to February 2023 [2] Updated 06 Jun 2023 |
| 06 Feb 2023 | Phase Change - Marketed | Launched for Asthma (In adolescents, In children, In adults) in United Kingdom (SC) prior to February 2023 [2] Updated 06 Jun 2023 |
| 06 Feb 2023 | Phase Change - Marketed | Launched for Asthma (In children) in Japan (SC) prior to February 2023 [2] Updated 06 Jun 2023 |
| 06 Feb 2023 | Phase Change - Marketed | Launched for Asthma in New Zealand, Singapore, Turkey, Hong Kong (SC) prior to February 2023 [2] Updated 06 Jun 2023 |
| 06 Feb 2023 | Phase Change - Marketed | Launched for Nasal polyps (Adjunctive treatment, In adults) in USA, Austria, Belgium, Chile, Czech Republic, Denmark, Finland, France, Greece, Ireland, Norway, Poland, Portugal, Spain, Sweden, Netherlands, Hungary, Germany (SC) prior to February 2023 [2] Updated 06 Jun 2023 |
| 09 Dec 2022 | Trial Update | University of North Carolina in collaboration with GlaxoSmithKline completes a phase-II trial in Eosinophilic oesophagitis (In adults, In adolescents) in USA (SC) (NCT03656380) Updated 27 Dec 2022 |
| 07 Sep 2022 | Trial Update | GlaxoSmithKline completes a phase-III clinical trial in Asthma (Adjunctive treatment, In adolescents, In adults) in China (SC) (NCT03562195) Updated 31 Oct 2022 |
| 14 Jul 2022 | Phase Change - III | Phase-III clinical trials in Hypereosinophilic syndrome (Adjunctive treatment, In children, In adolescents) in Argentina (SC) (NCT04965636) Updated 26 Aug 2022 |
| 14 Jul 2022 | Phase Change - III | Phase-III clinical trials in Hypereosinophilic syndrome (Adjunctive treatment, In children, In adolescents) in USA (SC) (NCT04965636) Updated 26 Aug 2022 |
| 25 Feb 2022 | Scientific Update | Efficacy data from a phase-III trial in chronic rhinosinusitis with nasal polyps (CRSwNP) presented at the Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI-2022) [111] Updated 12 Apr 2022 |
| 31 Jan 2022 | Phase Change - III | Phase-III clinical trials in Hypereosinophilic syndrome (Adjunctive therapy, In children, In adolescents) in Spain (SC) (EudraCT2021-000933-15) Updated 16 Feb 2022 |
| 01 Dec 2021 | Biomarker Update | Biomarkers information updated Updated 03 Dec 2021 |
| 17 Nov 2021 | Phase Change - Marketed | Launched for Asthma (Adjunctive treatment, In adolescents, In adults) in Canada, prior to November 2021 (IV) Updated 17 Nov 2021 |
| 08 Nov 2021 | Phase Change - Registered | Registered for Nasal polyps (Adjunctive treatment) in Canada (SC) [101] Updated 11 Nov 2021 |
| 01 Nov 2021 | Phase Change - Preregistration | Preregistration for Nasal polyps (Adjunctive treatment) in Canada (SC) before November 2021 [101] Updated 11 Nov 2021 |
| 13 Oct 2021 | Phase Change - Registered | Registered for Churg-Strauss syndrome (Adjunctive treatment, In adolescents, In adults, In children) in European Union (SC) [72] Updated 25 Jan 2023 |
| 13 Oct 2021 | Phase Change - Registered | Registered for Hypereosinophilic syndrome (Adjunctive treatment, In adults) in European Union (SC) [72] Updated 25 Jan 2023 |
| 13 Oct 2021 | Phase Change - Registered | Registered for Nasal polyps (Adjunctive treatment, In adults) in European Union (SC) [72] Updated 25 Jan 2023 |
| 06 Oct 2021 | Trial Update | GlaxoSmithKline plans an investigator-initiated pilot clinical trial for DRESS syndrome in Australia (SC) in November 2021 (ACTRN12621001333808 ) Updated 03 Jan 2022 |
| 16 Sep 2021 | Phase Change - Preregistration | Preregistration for Hypereosinophilic syndrome (Adjunctive treatment) in Canada, prior to September 2021 (SC) [82] Updated 17 Sep 2021 |
| 16 Sep 2021 | Phase Change - Registered | Registered for Hypereosinophilic syndrome (Adjunctive treatment) in Canada (SC) [82] Updated 17 Sep 2021 |
| 05 Sep 2021 | Scientific Update | Efficacy data from a phase III SYNAPSE trial in Nasal polyps (Adjunctive treatment) presented at the 31st Annual Congress of the European Respiratory Society (ERS-2021) [103] Updated 14 Feb 2022 |
| 30 Jul 2021 | Phase Change - Registered | Registered for Nasal polyps (Adjunctive treatment, In adults) in USA (SC) [99] Updated 02 Aug 2021 |
| 16 Jul 2021 | Trial Update | GlaxoSmithKline plans the phase III SPHERE trial for Hypereosinophilic syndrome (In children, In adolescents) in January 2022 (NCT04965636) Updated 16 Feb 2022 |
| 09 Jun 2021 | Scientific Update | Updated safety and efficacy data from a phase III extension trial in Hypereosinophilic syndrome presented at the 26th Congress of the European Haematology Association (EHA-2021) [87] Updated 05 Aug 2021 |
| 14 May 2021 | Scientific Update | Efficacy data from a phase III trial in Hypereosinophilic syndrome presented at the 117th International Conference of the American Thoracic Society (ATS-2021) [96] Updated 03 Jul 2021 |
| 14 May 2021 | Scientific Update | Safety and efficacy data from a phase III extension trial in Hypereosinophilic syndrome presented at the 117th International Conference of the American Thoracic Society (ATS-2021) [88] Updated 03 Jul 2021 |
| 14 May 2021 | Scientific Update | Updated efficacy data from the phase III SYNAPSE trial in Nasal polyps presented at the 117th International Conference of the American Thoracic Society (ATS-2021) [104] Updated 03 Jul 2021 |
| 29 Apr 2021 | Trial Update | National Institute of Allergy and Infectious Diseases in collaboration with GlaxoSmithKline completes phase II clinical trial in Asthma (Adjunctive treatment, In children, In adolescents) in USA (SC) in April 2021 (NCT03292588) Updated 06 May 2021 |
| 21 Apr 2021 | Scientific Update | Efficacy data from the phase III SYNAPSE trial in Nasal polyps presented at the Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI-2021) [106] [105] Updated 22 Apr 2021 |
| 26 Feb 2021 | Scientific Update | Efficacy data from a phase-III clinical trial in Hypereosinophilic syndrome presented at the Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI-2021) [95] Updated 22 Apr 2021 |
| 08 Feb 2021 | Phase Change - III | Phase-III clinical trials in Nasal polyps in China (SC) (NCT04607005) Updated 26 Feb 2024 |
| 08 Feb 2021 | Phase Change - III | Phase-III clinical trials in Nasal polyps in Japan (SC) (NCT04607005) Updated 07 Jun 2021 |
| 08 Feb 2021 | Phase Change - III | Phase-III clinical trials in Nasal polyps in Russia (SC) (NCT04607005) Updated 07 Jun 2021 |
| 08 Dec 2020 | Phase Change - Preregistration | Preregistration for Nasal polyps (Adjunctive treatment) in USA (SC) before December 2020 [100] (GlaxoSmithKline pipeline, January 2021) Updated 06 Jan 2021 |
| 08 Dec 2020 | Regulatory Status | US FDA accepts regulatory filing for Nasal polyps (Adjunctive treatment) for review [100] Updated 06 Jan 2021 |
| 13 Nov 2020 | Scientific Update | Efficacy data from the phase III trial for Nasal polyps (Adjunctive treatment) presented at the Annual Scientific Meeting of the American College of Allergy, Asthma & Immunology (ACAAI-2020) [107] Updated 08 Jan 2021 |
| 29 Oct 2020 | Phase Change - Preregistration | Preregistration for Churg-Strauss syndrome (Adjunctive treatment) in European Union (SC) [73] Updated 04 Nov 2020 |
| 29 Oct 2020 | Phase Change - Preregistration | Preregistration for Hypereosinophilic syndrome (Adjunctive treatment) in European Union (SC) [73] Updated 04 Nov 2020 |
| 29 Oct 2020 | Phase Change - Preregistration | Preregistration for Nasal polyps (associated with chronic rhinosinusitis ) (Adjunctive treatment) in European Union (SC) [73] Updated 04 Nov 2020 |
| 29 Oct 2020 | Regulatory Status | European Medicines Agency accepts regulatory filings for mepolizumab for Hypereosinophilic syndrome, Churg-Strauss syndrome and Nasal polyps for review [73] Updated 04 Nov 2020 |
| 28 Oct 2020 | Trial Update | GlaxoSmithKline plans the phase III MERIT trial in Nasal polyps and Rhinosinusitis in January 2021 (SC, Injection) (NCT04607005) Updated 07 Jun 2021 |
| 01 Oct 2020 | Phase Change - Discontinued(I/II) | Discontinued - Phase-I/II for Eosinophilic oesophagitis (In adolescents, In children) in Australia, Canada, USA, United Kingdom (IV), before October 2020 (GlaxoSmithKline pipeline, October 2020) Updated 01 Oct 2020 |
| 01 Oct 2020 | Phase Change - Discontinued(I/II) | Discontinued - Phase-I/II for Eosinophilic oesophagitis in Switzerland (IV), before October 2020 (GlaxoSmithKline pipeline, October 2020) Updated 01 Oct 2020 |
| 01 Oct 2020 | Phase Change - Discontinued(II) | Discontinued - Phase-II for Atopic dermatitis (In the elderly, In adults) in Canada, USA (SC), before October 2020 (GlaxoSmithKline pipeline, October 2020) Updated 01 Oct 2020 |
| 28 Sep 2020 | Phase Change - Marketed | Launched for Asthma (In adolescents, In adults, In children, Adjunctive treatment) in Greece (SC), prior to September 2020 Updated 28 Feb 2023 |
| 28 Sep 2020 | Phase Change - Registered | Registered for Hypereosinophilic syndrome (In adolescents, In adults) in USA (SC) [84] [83] Updated 29 Sep 2020 |
| 07 Sep 2020 | Scientific Update | Efficacy data from the phase III COMET trial in Asthma presented at 30th Annual Congress of the European Respiratory Society (ERS-2020) [40] Updated 15 Dec 2020 |
| 27 Jun 2020 | Scientific Update | Safety and adverse event data from a phase III COMET trial in Asthma presented at 116th International Conference of the American Thoracic Society (ATC-2020) [38] Updated 14 Jul 2020 |
| 16 Jun 2020 | Trial Update | GlaxoSmithKline re-initiates a phase III MATINEE trial in Chronic obstructive pulmonary disease (Adjunctive treatment) in USA, Denmark, Israel, Hungary, New Zealand, Germany, Netherlands, Spain, Australia, Belgium, Canada, Israel, Poland and United Kingdom (NCT04133909) Updated 26 Jun 2020 |
| 29 May 2020 | Regulatory Status | Mepolizumab receives priority review status for Hypereosinophilic syndrome in USA [70] Updated 29 May 2020 |
| 15 May 2020 | Scientific Update | Safety data from a phase III trial in Hypereosinophilic syndrome presented at the 116th International Conference of the American Thoracic Society (ATS-2020) [91] Updated 14 Jul 2020 |
| 29 Apr 2020 | Regulatory Status | GlaxoSmithKline anticipates regulatory submissions for Nasal polyps in second half of 2020 [118] Updated 06 Jan 2021 |
| 08 Apr 2020 | Trial Update | GlaxoSmithKline suspends phase III trial in Chronic obstructive pulmonary disease (Adjunctive treatment, In adults, In the elderly) in Hungary (SC) due to COVID-19 pandemic ( NCT04133909) Updated 17 Apr 2020 |
| 06 Apr 2020 | Scientific Update | Efficacy and adverse events data from the phase III SYNAPSE trial for Nasal polyps released by GlaxoSmithKline [109] Updated 07 Apr 2020 |
| 27 Mar 2020 | Phase Change - Preregistration | Preregistration for Hypereosinophilic syndrome in USA (SC) (GlaxoSmithKline pipeline, April 2020) Updated 05 May 2020 |
| 25 Mar 2020 | Phase Change - Registered | Registered for Asthma (In children) in Japan (SC) [24] Updated 08 Apr 2021 |
| 17 Mar 2020 | Phase Change - Registered | Registered for Asthma (Adjunctive treatment, In adolescents, In adults) in Canada (IV) Updated 20 Mar 2020 |
| 12 Mar 2020 | Trial Update | GlaxoSmithKline initiates enrolment in a phase III trial for Churg-Strauss syndrome (Adjunctive treatment) in Canada, France, Japan, USA before March 2020(NCT03298061) Updated 09 Dec 2020 |
| 30 Dec 2019 | Trial Update | GlaxoSmithKline completes a phase III extension trial for Hypereosinophilic syndrome (In adolescents, In adults, In the elderly) in Argentina, Belgium, Brazil, France, Germany, Italy, Mexico, Poland, Romania, Russia, Spain, United Kingdom and USA (SC) (NCT03306043) Updated 21 Jan 2020 |
| 11 Dec 2019 | Trial Update | GlaxoSmithKline and Bristol-Myers Squibb complete the phase III SYNAPSE trial for Nasal polyps (Adjunctive treatment) in Argentina, Canada, Germany, South Korea, Netherlands, Romania, Russia, Sweden, United Kingdom and USA (SC) (NCT03085797) Updated 22 Jan 2020 |
| 13 Nov 2019 | Regulatory Status | Mepolizumab receives Fast Track designation for Hypereosinophilic syndrome [SC,Injection] in USA, prior to November 2019 [92] Updated 26 Nov 2019 |
| 13 Nov 2019 | Scientific Update | Efficacy data from a phase III trial in Hypereosinophilic syndrome released by GlaxoSmithKline [92] Updated 26 Nov 2019 |
| 30 Oct 2019 | Phase Change - III | Phase-III clinical trials in Chronic obstructive pulmonary disease (Adjunctive treatment) in Israel, New Zealand (SC) NCT04133909) Updated 26 Jun 2020 |
| 30 Oct 2019 | Trial Update | GlaxoSmithKline initiates a phase III MATINEE trial in Chronic obstructive pulmonary disease (Adjunctive treatment) in USA, Denmark, Germany, Netherlands, Spain, Australia, Belgium, Canada, Israel, Poland and United Kingdom (NCT04133909) Updated 26 Jun 2020 |
| 09 Oct 2019 | Regulatory Status | Health Canada approves two new methods for administration of mepolizumab, an autoinjector and a pre-filled safety syringe, in patients with Severe eosinophilic asthma and Churg-Strauss syndrome [4] Updated 16 Oct 2019 |
| 28 Sep 2019 | Regulatory Status | Mepolizumab available in France as a part of early access programme (Temporary Authorization for Utilization (ATU)) for Eosinophilic asthma before European approval [11] Updated 04 Mar 2020 |
| 12 Sep 2019 | Phase Change - Registered | Registered for Asthma (Adjunctive treatment, In children) in USA (SC) [22] Updated 16 Sep 2019 |
| 08 Aug 2019 | Trial Update | GlaxoSmithKline completes a phase III trial for Hypereosinophilic syndrome (Adjunctive treatment, In adolescents, In adults, In the elderly) in Germany, France, Italy, Poland, Romania, USA, Belgium, Spain, the United Kingdom, Argentina, Brazil, France, Italy, Mexico, Poland, Romania, Russia (SC) (NCT02836496) Updated 04 Sep 2019 |
| 02 Aug 2019 | Regulatory Status | The European Commission approves two new methods for administration of mepolizumab, an autoinjector and a pre-filled safety syringe for Asthma [8] Updated 07 Aug 2019 |
| 01 Aug 2019 | Regulatory Status | GlaxoSmithKline expects the first European launches of the two new methods for administering mepolizumab, an autoinjector and a pre-filled safety syringe for Asthma in August 2019 [8] Updated 07 Aug 2019 |
| 29 Jul 2019 | Phase Change - III | Phase-III clinical trials in Chronic obstructive pulmonary disease (Adjunctive treatment, In adults, In the elderly) in Hungary (SC) (EudraCT2018-001540-56) Updated 08 Aug 2019 |
| 24 Jul 2019 | Trial Update | GlaxoSmithKline completes a phase III trial in Asthma in USA, Australia, Canada, France, Germany, Japan, South Korea, Netherlands, Romania, Russia, Spain, Argentina, Poland, and Ukraine (SC) (NCT02555371) Updated 19 Aug 2019 |
| 06 Jun 2019 | Regulatory Status | The US FDA approves two new methods for administration of mepolizumab, an autoinjector and a pre-filled safety syringe, in patients with Severe eosinophilic asthma and Churg-Strauss syndrome [5] Updated 12 Jun 2019 |
| 04 Jun 2019 | Regulatory Status | The European Medicines Agency’s Committee for Medicinal Products for Human Use issues positive opinion for two new methods for administration of mepolizumab, an a pre-filled pen and a pre-filled safety syringe, in patients with severe eosinophilic Asthma [9] Updated 20 Jun 2019 |
| 17 May 2019 | Scientific Update | Efficacy, adverse events, pharmacokinetics and immunogenicity data from a phase III trial (In volunteers) presented at the 115th International Conference of the American Thoracic Society (ATS-2019) [32] Updated 23 Sep 2019 |
| 20 Mar 2019 | Phase Change - II | Phase-II clinical trials in Eosinophilic oesophagitis (In adults, In adolescents) in USA (SC) (NCT03656380) Updated 22 Feb 2019 |
| 22 Feb 2019 | Scientific Update | Pharmacodynamics data from a phase III trial in Churg-Strauss syndrome (Eosinophilic granulomatosis with polyangiitis (EGPA)) presented at the Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI-2019) [81] Updated 19 Mar 2019 |
| 19 Nov 2018 | Phase Change - Preregistration | Preregistration for Asthma (In children, Adjunctive treatment) in USA (SC) [23] Updated 22 Nov 2018 |
| 13 Sep 2018 | Phase Change - III | Phase-III clinical trials in Asthma (Adjunctive treatment, In adolescents, In adults) in China (SC) (NCT03562195) Updated 05 Oct 2018 |
| 10 Sep 2018 | Phase Change - Registered | Registered for Churg-Strauss syndrome (Adjunctive treatment) in Canada (SC) [75] Updated 11 Oct 2018 |
| 10 Sep 2018 | Scientific Update | Pooled efficacy data from clinical trials in Asthma released by GlaxoSmithKline Updated 12 Sep 2018 |
| 07 Sep 2018 | Regulatory Status | GlaxoSmithKline receives complete response letter from the US FDA for mepolizumab in Chronic obstructive pulmonary disease (COPD) [58] Updated 10 Sep 2018 |
| 30 Aug 2018 | Phase Change - Registered | Registered for Asthma (Adjunctive treatment, In adolescents, In children) in European Union, Norway, Liechtenstein and Iceland (SC) [10] Updated 06 Sep 2018 |
| 27 Jul 2018 | Phase Change - Preregistration | Preregistration for Asthma (In children, Adjunctive treatment, In adolescents) in European Union (SC) [12] before July 2018 Updated 06 Sep 2018 |
| 27 Jul 2018 | Regulatory Status | Committee for Medicinal Products for Human Use (CHMP) recommends approval of mepolizumab for eosinophilic Asthma in European Union [12] Updated 31 Jul 2018 |
| 26 Jul 2018 | Regulatory Status | Pulmonary Allergy Drugs Advisory Committee of US FDA does not recommend approval of mepolizumab for Chronic obstructive pulmonary disease (Adjunctive treatment) [59] Updated 27 Jul 2018 |
| 25 Jul 2018 | Regulatory Status | FDA assigns PDUFA action date of 07 /09/2018 for mepolizumab for Chronic obstructive pulmonary disease (Adjunctive-treatment) [59] Updated 11 Nov 2021 |
| 19 Jun 2018 | Trial Update | GlaxoSmithKline plans a phase III trial for Asthma in August 2018 , (NCT03562195) Updated 05 Oct 2018 |
| 25 May 2018 | Phase Change - Registered | Registered for Churg-Strauss syndrome (Adjunctive treatment) in Japan (SC) [74] Updated 11 Oct 2018 |
| 21 May 2018 | Scientific Update | Efficacy and adverse events data from the phase III COLUMBA trial presented at the 114th International Conference of the American Thoracic Society (ATS-2018) [47] Updated 28 May 2018 |
| 31 Jan 2018 | Trial Update | GlaxoSmithKline completes a phase II trial in Asthma (In children) in Japan, Poland, United Kingdom and USA (SC) (NCT02377427) Updated 16 Apr 2018 |
| 12 Dec 2017 | Phase Change - Registered | Registered for Churg-Strauss syndrome (Adjunctive treatment) in USA (SC) [68] Updated 15 Dec 2017 |
| 12 Dec 2017 | Regulatory Status | Mepolizumab received priority review status for Churg-Strauss syndrome in USA, before December 2017 [68] Updated 15 Dec 2017 |
| 06 Dec 2017 | Trial Update | GlaxoSmithKline terminates phase II trial in Atopic dermatitis (In the elderly, In adults) in USA and Canada (SC) as the study reached pre-determined futility criteria following interim analysis (NCT03055195) Updated 13 Feb 2018 |
| 30 Nov 2017 | Trial Update | GlaxoSmithKline completes a phase III trial in Asthma (Adjunctive treatment, In adolescents, In adults) in Germany, Australia, Canada, Russia and United Kingdom, USA and Sweden (SC) (NCT03099096) (EudraCT2016-001832-36) Updated 05 Jan 2018 |
| 13 Nov 2017 | Trial Update | GlaxoSmithKline initiates enrolment in a phase III extension trial for Hypereosinophilic syndrome (In adolescents, In adults, In the elderly) in Belgium, Germany, Spain (SC) (EudraCT2017-000184-32) (NCT03306043) Updated 15 Dec 2017 |
| 07 Nov 2017 | Phase Change - Preregistration | Preregistration for Chronic obstructive pulmonary disease (Adjunctive treatment) in USA (SC) [60] Updated 08 Nov 2017 |
| 31 Oct 2017 | Phase Change - II | Phase-II clinical trials in Asthma (Adjunctive treatment, In children, In adolescents) in USA (SC) (NCT03292588) Updated 16 Nov 2017 |
| 05 Oct 2017 | Trial Update | GlaxoSmithKline completes a phase III trial in Asthma in USA, Argentina, Australia, Belgium, Canada, Chile, Czech Republic, France, Germany, Italy, Japan, Mexico, Russia, South Korea, Spain, Ukraine and United Kingdom (NCT02135692) Updated 01 Dec 2017 |
| 12 Sep 2017 | Regulatory Status | GlaxoSmithKline plans to file an regulatory application for Chronic obstructive pulmonary disease in 2017 [65] Updated 08 Nov 2017 |
| 12 Sep 2017 | Scientific Update | Safety and efficacy data from the two phase III METREX and METREO trials in Chronic obstructive pulmonary disease released by GlaxoSmithKline [65] Updated 14 Sep 2017 |
| 11 Aug 2017 | Trial Update | GlaxoSmithKline completes a phase III trial in pharmacokinetics trial for Asthma (In volunteers) in USA, Germany and United Kingdom (SC) (NCT03014674) Updated 07 Sep 2017 |
| 08 Aug 2017 | Trial Update | GlaxoSmithKline completes a phase III trial in Asthma (Adjunctive treatment, In adolescents, In adults) in USA, Canada, the Netherlands, Sweden and Russia (NCT03021304) Updated 30 Aug 2017 |
| 25 Jul 2017 | Trial Update | GlaxoSmithKline plans a phase III trial for Hypereosinophilic syndrome (In adolescents, In adults, In the elderly) in Argentina, Belgium, Brazil, Mexico, Russia and USA (EudraCT2017-000184-32) Updated 15 Dec 2017 |
| 28 Jun 2017 | Phase Change - Preregistration | Preregistration for Churg-Strauss syndrome (Adjunctive treatment) in USA (SC) [69] Updated 05 Jul 2017 |
| 28 Jun 2017 | Regulatory Status | GlaxoSmithKline announces intention to submit regulatory filings in other countries for Churg-Strauss syndrome in 2017 and 2018 [69] Updated 05 Jul 2017 |
| 06 Jun 2017 | Trial Update | Johannes Gutenberg University Mainz terminates the phase III MEMORY trial for Asthma in Germany (SC) (EudraCT2015-001868-19) Updated 12 Jun 2017 |
| 31 May 2017 | Trial Update | GlaxoSmithKline completes a long term extension phase III trial for Asthma in USA, Argentina, Australia, Canada, Chile, France, Germany, South Korea, Poland, Romania, Russia, Ukraine and United Kingdom (SC) (NCT01691859) Updated 06 Jul 2017 |
| 25 May 2017 | Phase Change - III | Phase-III clinical trials in Nasal polyps (Adjunctive treatment) in Argentina, Australia, Canada, South Korea, Netherlands, Romania, Russia, United Kingdom (SC) (NCT03085797) Updated 22 Jan 2020 |
| 25 May 2017 | Phase Change - III | Phase-III clinical trials in Nasal polyps (Combination therapy) in Sweden, Germany, USA (SC) (NCT03085797) Updated 22 Jun 2017 |
| 17 May 2017 | Scientific Update | Positive adverse events and efficacy data from a phase III trial in Churg-Strauss syndrome (eosinophilic granulomatosis with polyangiitis) released by GlaxoSmithKline [80] Updated 02 Jun 2017 |
| 12 May 2017 | Scientific Update | Preliminary efficacy and adverse events data from two phase III METREX and METREO trials in Chronic obstructive pulmonary disease released by GlaxoSmithKline [63] Updated 30 May 2017 |
| 06 Apr 2017 | Trial Update | GlaxoSmithKline plans a phase III trial for Asthma (NCT03099096) Updated 02 Jun 2017 |
| 23 Mar 2017 | Trial Update | GlaxoSmithKline plans a phase III trial for Nasal polyps (NCT03085797) Updated 25 Jul 2017 |
| 23 Mar 2017 | Trial Update | GlaxoSmithKline initiates enrolment in a phase III trial for Churg-Strauss syndrome (Adjunctive treatment) in Germany (EudraCT2014-003162-25) before March 2017 Updated 24 Mar 2017 |
| 21 Mar 2017 | Phase Change - II | Phase-II clinical trials in Atopic dermatitis (In the elderly, In adults) in USA (SC) (NCT03055195) Updated 13 Feb 2018 |
| 21 Mar 2017 | Phase Change - II | Phase-II clinical trials in Atopic dermatitis (In adults, In the elderly) in Canada (SC) (NCT03055195) Updated 13 Apr 2017 |
| 16 Mar 2017 | Trial Update | GlaxoSmithKline plans a phase II trial for Atopic dermatitis in USA (NCT03055195) Updated 11 Nov 2021 |
| 16 Mar 2017 | Trial Update | GlaxoSmithKline initiates enrolment in a phase III trial in Asthma (Adjunctive treatment, In adolescents, In adults) in Germany, Australia, Canada, Russia and United Kingdom (SC) (NCT03099096) (EudraCT2016-001832-36)after March 2017 Updated 05 Jan 2018 |
| 16 Mar 2017 | Phase Change - III | Phase-III clinical trials in Asthma (Adjunctive treatment, In adolescents, In adults) in Sweden (SC) (NCT03099096) Updated 02 Jun 2017 |
| 16 Mar 2017 | Trial Update | GlaxoSmithKline initiates a phase-III trial in Asthma (Adjunctive treatment, In adolescents, In adults) in USA (SC) (NCT03099096) Updated 02 Jun 2017 |
| 07 Mar 2017 | Phase Change - III | Phase-III clinical trials in Hypereosinophilic syndrome (Adjunctive treatment, In adolescents, In adults, In the elderly) in Russia, Mexico, Brazil, Argentina (SC) (NCT02836496) Updated 04 Sep 2019 |
| 07 Mar 2017 | Trial Update | GlaxoSmithKline initiates enrolment in a phase III trial for Hypereosinophilic syndrome (Adjunctive treatment, In adolescents, In adults, In the elderly) inFrance, Italy, Poland, Romania, USA, Belgium, Spain and the United Kingdom (SC) (NCT02836496) Updated 04 Sep 2019 |
| 06 Mar 2017 | Scientific Update | Adverse events and efficacy data from the phase IIIb MUSCA trial in Asthma released by GlaxoSmithKline [119] Updated 08 Mar 2017 |
| 01 Feb 2017 | Phase Change - III | Phase-III clinical trials in Asthma (In adolescents, In adults, Adjunctive treatment) in Sweden (SC) (NCT03021304) Updated 30 Aug 2017 |
| 01 Feb 2017 | Trial Update | GlaxoSmithKline initiates a phase IIIa trial in Asthma (Adjunctive treatment, In adolescents, In adults) in Canada and Russia (NCT03021304) Updated 30 Aug 2017 |
| 01 Feb 2017 | Trial Update | GlaxoSmithKline initiates a phase IIIa trial in Asthma (In adolescents, In adults) in Netherlands(EudraCT2016-001831-10) Updated 24 Feb 2017 |
| 01 Feb 2017 | Trial Update | GlaxoSmithKline initiates a phase IIIa trial in Asthma (Adjunctive treatment, In adolescents, In adults) in USA (NCT03021304) Updated 16 Feb 2017 |
| 12 Jan 2017 | Trial Update | GlaxoSmithKline plans a phase IIIa trial in Asthma (Adjunctive treatment, In adolescents, In adults) in USA, Canada, Russia, the Netherlands and Sweden (NCT03021304) Updated 19 Jan 2017 |
| 05 Jan 2017 | Trial Update | GlaxoSmithKline initiates a phase III pharmacokinetics trial for Asthma (In volunteers) in Germany (SC) (EudraCT2016-002405-19) Updated 12 Jan 2017 |
| 01 Jan 2017 | Trial Update | GlaxoSmithKline completes the 117113 phase III trial in Chronic obstructive pulmonary disease in USA, Argentina, Chile, Canada, Denmark, Germany, Netherlands, Japan, Romania, Ukraine, South Korea,Taiwan, Slovakia and United Kingdom (NCT02105961) Updated 17 Mar 2017 |
| 01 Jan 2017 | Trial Update | GlaxoSmithKline completes a phase III trial in Chronic obstructive pulmonary disease (Adjunctive treatment) in US, Australia, Belgium, Canada, Czech Republic, Estonia, France, Greece, Italy, Mexico, Norway, Peru, Poland, Russia, Sweden and Spain (NCT02105948) Updated 16 Feb 2017 |
| 01 Jan 2017 | Trial Update | GlaxoSmithKline initiates a phase III pharmacokinetics trial for Asthma (In volunteers) in USA and United Kingdom (SC) (NCT03014674) Updated 16 Feb 2017 |
| 23 Nov 2016 | Scientific Update | Adverse events and efficacy data from a phase III trial in Churg-Strauss syndrome released by GlaxoSmithKline [78] Updated 28 Nov 2016 |
| 07 Oct 2016 | Phase Change - Registered | Registered for Asthma (Adjunctive treatment, In adolescents, In adults) in South Korea, Chile, Taiwan, Switzerland (SC) before October 2016 [49] Updated 13 Oct 2016 |
| 01 Sep 2016 | Trial Update | GlaxoSmithKline completes a phase III trial in in Churg-Strauss syndrome in USA, Belgium, Canada, France, Germany, Italy, Japan, Spain, and United Kingdom (NCT02020889) Updated 22 Nov 2016 |
| 20 Jul 2016 | Trial Update | GlaxoSmithKline plans a phase III trial for Nasal polyps (Treatment-experienced, In adolescents, In adults) in United Kingdom (SC) (UKCRN31173) Updated 28 Jul 2016 |
| 14 Jul 2016 | Trial Update | GlaxoSmithKline plans a phase III trial for Hypereosinophilic Syndrome (Adjunctive treatment, In adolescents, In adults, In the elderly) in Russia, USA, Spain, Italy, Romania, Argentina, France, United Kingdom, Germany, Mexico, Poland and Sweden (SC) (NCT02836496) Updated 21 Jul 2016 |
| 01 Jun 2016 | Trial Update | GlaxoSmithKline completes a phase III trial for Asthma (Adjunctive treatment, In adolescents, In adults) in USA, Argentina, Belgium, Bulgaria, Canada, Czech Republic, Estonia, France, Germany, Norway, Greece, Italy, the Netherlands, Russia, Slovakia, Spain, Ukraine and United Kingdom (SC) (NCT02281318; EudraCT2014-002513-27) Updated 29 Jun 2016 |
| 29 Mar 2016 | Phase Change - Registered | Registered for Asthma (Adjunctive treatment, In adolescents, In adults) in Japan (SC) [25] Updated 30 Mar 2016 |
| 07 Mar 2016 | Scientific Update | Efficacy data from a phase II and phase III trial in Asthma presented at the Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI-2016) [120] Updated 10 Mar 2016 |
| 05 Mar 2016 | Phase Change - Preregistration | Preregistration for Asthma (Adjunctive treatment, In adolescents, In adults) in Australia (SC) before March 2016 [18] Updated 15 Mar 2016 |
| 05 Mar 2016 | Phase Change - Registered | Registered for Asthma (Adjunctive treatment, In adolescents, In adults) in Australia (SC) [18] Updated 15 Mar 2016 |
| 05 Mar 2016 | Scientific Update | Safety and efficacy data from a phase III extension, COSMOS study in Asthma presented at the Annual Meeting of the American Academy of Allergy , Asthma and Immunology (AAAAI-2016) [18] Updated 15 Mar 2016 |
| 04 Mar 2016 | Scientific Update | Efficacy data from post-hoc analysis of a phase III MESNA trial in Asthma presented at the Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI-2016) [121] Updated 17 Mar 2016 |
| 04 Mar 2016 | Scientific Update | Updated efficacy and adverse events data from a phase III MESNA and COSMOS trial in Asthma presented at the Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI-2016) (3176232; 3176295) Updated 17 Mar 2016 |
| 07 Jan 2016 | Phase Change - III | Phase-III clinical trials in Asthma (In adolescents, In adults, In the elderly, Adjunctive treatment) in Argentina, Poland, Romania and Ukraine (SC) (NCT02555371) Updated 19 Aug 2019 |
| 07 Jan 2016 | Trial Update | GlaxoSmithKline initiates a phase III trial for Asthma (Adjunctive treatment, In adolescents, In adults, In the elderly) in Australia, Canada, France, Germany, Japan, South Korea, Netherlands, Russia and Spain (SC) (NCT02555371) Updated 26 May 2017 |
| 07 Jan 2016 | Trial Update | GlaxoSmithKline initiates a phase III trial for Asthma (Adjunctive treatment, In adolescents, In adults, In the elderly) in USA (SC) (NCT02555371) Updated 25 Jan 2016 |
| 10 Dec 2015 | Phase Change - Registered | Registered for Asthma (Adjunctive treatment, In adults) in Canada (SC) [6] Updated 12 Dec 2015 |
| 02 Dec 2015 | Phase Change - Registered | Registered for Asthma (Adjunctive treatment, In adults) in European Union, Norway, Iceland, Liechtenstein (SC) [13] Updated 12 Dec 2015 |
| 02 Dec 2015 | Phase Change - Marketed | Launched for Asthma (Adjunctive treatment, In adolescents, In adults) in USA (SC) - First global launch [17] Updated 05 Dec 2015 |
| 01 Dec 2015 | Trial Update | GlaxoSmithKline Research & Development initiates the phase III/IV OSMO trial for Asthma (Adjunctive treatment, In adolescents, In adults) in Netherlands, USA, Argentina, Belgium, Canada, France, Germany, Spain and Sweden (SC) (EudraCT2015-003697-32) (NCT02654145) Updated 25 Jan 2016 |
| 01 Dec 2015 | Phase Change - Preregistration | Preregistration for Asthma (Adjunctive treatment, In adults) in Canada (SC) before December 2015 [6] Updated 12 Dec 2015 |
| 04 Nov 2015 | Phase Change - Registered | Registered for Asthma (Adjunctive treatment, In adolescents, In adults) in USA (SC) Updated 06 Nov 2015 |
| 15 Oct 2015 | Trial Update | Johannes Gutenberg University Mainz initiates enrolment in the phase III MEMORY trial for Asthma in Germany (SC) (EudraCT2015-001868-19) Updated 03 Nov 2015 |
| 24 Sep 2015 | Regulatory Status | The Committee of Medicinal Products for Human Use recommends approval of Mepolizumab for severe eosinophilic Asthma in European Union (SC) [14] Updated 28 Sep 2015 |
| 23 Sep 2015 | Trial Update | GlaxoSmithKline plans a phase III trial for Asthma (Adjunctive treatment, In adolescents, In adults) in Argentina, Australia, Belgium, Canada, Chile, Czech Republic, France, Germany, Japan, the Netherlands, Poland, Romania, Russia, South Korea, Spain, Ukraine and USA (SC) (NCT02555371) Updated 23 Sep 2015 |
| 01 Sep 2015 | Trial Update | McMaster University completes a phase III clinical trials in Chronic obstructive pulmonary disease (In adults, In the elderly) in Canada (IV) (NCT01463644) Updated 02 Oct 2015 |
| 31 Aug 2015 | Trial Update | EudraCT2014-003162-25 - Added trial initiation info Updated 31 Aug 2015 |
| 25 Aug 2015 | Trial Update | GlaxoSmithKline initiates a phase II trial in Asthma (In children) in USA (SC) (NCT02377427) Updated 16 Apr 2018 |
| 01 Aug 2015 | Phase Change - II | Phase-II clinical trials in Asthma (In children) in Poland (SC) (NCT02377427) Updated 16 Apr 2018 |
| 01 Aug 2015 | Phase Change - III | Phase-III clinical trials in Asthma (In adolescents, In children, In adults) in Australia, Switzerland (SC) (NCT02543112) Updated 27 Apr 2017 |
| 01 Aug 2015 | Phase Change - III | Phase-III clinical trials in Asthma (In adolescents, In children, In adults) in Argentina, Bulgaria, Czech Republic, Estonia, France, Germany, Greece, Italy, Norway, Peru, Slovakia, Ukraine, United Kingdom, USA (SC) (NCT02543112) after August 2015 Updated 17 Feb 2017 |
| 01 Aug 2015 | Phase Change - III | Phase-III clinical trials in Asthma (In adolescents, In children, In adults) in Canada, Russia, Spain after August 2015 (SC) (NCT02543112) Updated 03 Nov 2015 |
| 01 Aug 2015 | Phase Change - II | Phase-II clinical trials in Asthma (In children) in Japan and the United Kingdom (SC) (NCT02377427) Updated 15 Oct 2015 |
| 01 Aug 2015 | Phase Change - III | Phase-III clinical trials in Asthma (In children, In adults, In adolescents) in Netherlands, Belgium (SC) (NCT02543112) Updated 01 Oct 2015 |
| 11 Jun 2015 | Regulatory Status | The US FDA sets PDUFA date of 04 November 2015 for BLA review for Asthma (In Adults) (SC) [20] Updated 30 Sep 2015 |
| 11 Jun 2015 | Regulatory Status | Pulmonary Allergy Drugs Advisory Committee of the US FDA recommends approval of mepolizumab in adults with asthma and does not recommend approval of the drug in adolescents with asthma [20] Updated 13 Jun 2015 |
| 26 May 2015 | Active Status Review | Mepolizumab (IV) is still in phase III development for Asthma in European Union, Japan and USA Updated 26 May 2015 |
| 26 May 2015 | Active Status Review | Mepolizumab is still available for compassionate use for Hypereosinophilic syndrome in USA, Australia, Belgium, Canada, France, Germany, Italy, Netherlands, Norway, Spain, Switzerland and United Kingdom Updated 26 May 2015 |
| 26 May 2015 | Active Status Review | Mepolizumab is still in phase II development for Nasal polyps in Netherlands, Belgium and United Kingdom Updated 26 May 2015 |
| 26 May 2015 | Active Status Review | Mepolizumab (SC, IV) is still in phase III development for Asthma in Australia, Argentina, Mexico, Russia, Canada, South Korea and Ukraine Updated 26 May 2015 |
| 22 May 2015 | Phase Change - Preregistration | Preregistration for Asthma (In adolescents, In adults, Adjunctive treatment) in Japan (SC) [26] Updated 25 May 2015 |
| 19 Mar 2015 | Trial Update | GlaxoSmithKline initiates enrolment in a phase III trial for Churg-Strauss syndrome (Adjunctive treatment) in Belgium (EudraCT2014-003162-25) after March 2015 Updated 22 Nov 2016 |
| 19 Mar 2015 | Trial Update | GlaxoSmithKline initiates enrolment in a phase III trial for Churg-Strauss syndrome (Adjunctive treatment) in United Kingdom (EudraCT2014-003162-25) Updated 31 Aug 2015 |
| 01 Mar 2015 | Trial Update | GlaxoSmithKline completes a long-term phase III extension trial in Asthma in Argentina, Australia, Belgium, Canada, Chile, Czech Republic, France, Germany, Italy, Japan, South Korea, Mexico, Netherlands, Poland, Russia, Spain, Ukraine, USA and United Kingdom (NCT01842607; EudraCT2012-001644-21) Updated 14 May 2015 |
| 26 Feb 2015 | Trial Update | GlaxoSmithKline plans a phase II trial for Asthma (In children) in USA, European Union and Japan (NCT02377427) Updated 09 Mar 2015 |
| 01 Dec 2014 | Phase Change - III | Phase-III clinical trials in Asthma (Adjunctive treatment, In adults, In adolescents) in Peru, Norway (SC) (NCT02281318) Updated 01 Oct 2015 |
| 01 Dec 2014 | Trial Update | GlaxoSmithKline initiates enrolment in a phase III trial for Asthma (Adjunctive treatment, In adolescents, In adults) in USA, Argentina, Belgium, Bulgaria, Canada, Czech Republic, Estonia, France, Germany, Norway, Greece, Italy, the Netherlands, Russia, Slovakia, Spain, Ukraine and United Kingdom (SC) (NCT02281318; EudraCT2014-002513-27) Updated 01 Oct 2015 |
| 01 Dec 2014 | Trial Update | GlaxoSmithKline completes a phase II trial in Nasal polyps in United Kingdom, Belgium and Netherlands (NCT01362244) Updated 10 Jan 2015 |
| 05 Nov 2014 | Phase Change - Preregistration | Preregistration for Asthma (In adolescents, In adults, Adjunctive treatment) in USA (SC) Updated 07 Nov 2014 |
| 05 Nov 2014 | Phase Change - Preregistration | Preregistration for Asthma (In adults, Adjunctive treatment) in European Union (SC) Updated 07 Nov 2014 |
| 05 Nov 2014 | Trial Update | GlaxoSmithKline plans a phase III trial for Asthma (Adjunctive therapy, In adults, In adolescents) in the US, the UK, Slovakia, Russia, Estonia, Italy, Bulgaria, Germany, Belgium, France, Norway, Argentina, Czech Republic, Spain, Ukraine, Greece, the Netherlands and Canada (NCT02281318) Updated 05 Nov 2014 |
| 08 Sep 2014 | Scientific Update | Efficacy and adverse events data from phase III trials in Asthma presented at the 24th Annual Congress of the European Respiratory Society (ERS-2014) [41] Updated 12 Sep 2014 |
| 01 May 2014 | Trial Update | GlaxoSmithKline initiates a long-term phase III extension trial for Asthma in USA, Australia and Belgium (NCT02135692) Updated 01 Jul 2014 |
| 29 Apr 2014 | Phase Change - III | Phase-III clinical trials in Chronic obstructive pulmonary disease (Adjunctive treatment) in Taiwan (SC) (NCT02105961) Updated 17 Mar 2017 |
| 29 Apr 2014 | Phase Change - III | Phase-III clinical trials in Chronic obstructive pulmonary disease (Adjunctive treatment) in Argentina, Chile, Denmark, Germany, Japan, Romania, Ukraine and United Kingdom (SC) Updated 12 Sep 2014 |
| 29 Apr 2014 | Phase Change - III | Phase-III clinical trials in Chronic obstructive pulmonary disease (Adjunctive treatment) in Czech Republic, France, Italy and Norway (SC) Updated 12 Sep 2014 |
| 29 Apr 2014 | Phase Change - III | Phase-III clinical trials in Chronic obstructive pulmonary disease (adjunctive treatment) in Australia, Belgium, Canada, Estonia, Greece, Poland, Slovakia, South Korea, Sweden and Spain (SC) Updated 01 Jul 2014 |
| 29 Apr 2014 | Phase Change - III | Phase-III clinical trials in Chronic obstructive pulmonary disease (add-on therapy) in USA (SC) Updated 01 May 2014 |
| 03 Apr 2014 | Active Status Review | GlaxoSmithKline plans a phase III trial for Chronic obstructive pulmonary disease (adjunctive treatment) in USA (NCT02105961) Updated 11 Apr 2014 |
| 03 Apr 2014 | Trial Update | GlaxoSmithKline plans a phase III trial for Chronic obstructive pulmonary disease (adjunctive treatment) in USA (NCT02105948) Updated 10 Apr 2014 |
| 01 Apr 2014 | Phase Change - III | Phase-III clinical trials in Chronic obstructive pulmonary disease (Adjunctive treatment) in Mexico, Peru, Russia after April 2014 (SC) (NCT02105948) Updated 02 Oct 2015 |
| 01 Apr 2014 | Phase Change - III | Phase-III clinical trials in Chronic obstructive pulmonary disease (Adjunctive treatment) in Netherlands after April 2014 (SC) (NCT02105961) Updated 02 Oct 2015 |
| 01 Apr 2014 | Phase Change - III | Phase-III clinical trials in Churg-Strauss syndrome in Belgium (SC) Updated 08 May 2014 |
| 01 Apr 2014 | Phase Change - III | Phase-III clinical trials in Churg-Strauss syndrome in Canada (SC) Updated 08 May 2014 |
| 01 Apr 2014 | Phase Change - III | Phase-III clinical trials in Churg-Strauss syndrome in France (SC) Updated 09 Apr 2014 |
| 01 Apr 2014 | Phase Change - III | Phase-III clinical trials in Churg-Strauss syndrome in Italy (SC) Updated 09 Apr 2014 |
| 14 Mar 2014 | Active Status Review | Mepolizumab is still in a phase II trial for Nasal polyps in the European Union. Updated 14 Mar 2014 |
| 12 Mar 2014 | Scientific Update | Efficacy and adverse events data from two phase III trials in Asthma released by GlaxoSmithKline [16] Updated 14 Mar 2014 |
| 28 Feb 2014 | Trial Update | GlaxoSmithKline completes a phase III trial in Asthma (Adjunctive treatment, In adolescents, In adults) in USA, Argentina, Australia, Belgium, Canada, Chile, the Czech Republic, France, Germany, Italy, Japan, Mexico, Russia, South Korea, Spain, Ukraine and United Kingdom (NCT01691521) Updated 15 May 2014 |
| 14 Feb 2014 | Phase Change - III | Phase-III clinical trials in Churg-Strauss syndrome in USA and Japan (SC) after February 2014 (NCT02020889) Updated 11 Dec 2014 |
| 14 Feb 2014 | Phase Change - III | Phase-III clinical trials in Churg-Strauss syndrome in Germany, Spain and the United Kingdom (SC) Updated 14 Mar 2014 |
| 01 Jan 2014 | Trial Update | GlaxoSmithKline completes phase-III clinical trials in Asthma (Adjunctive treatment, In adolescents, In adults) in USA, Canada, Australia, Belgium, France, Germany, Italy, Spain, Ukraine, United Kingdom, Chile, South Korea, Russia, Argentina, Mexico, Japan (IV) and (SC) (NCT01691521) Updated 07 Dec 2015 |
| 19 Dec 2013 | Trial Update | GSK plans a phase-III trial for Churg-Strauss syndrome in Belgium (NCT02020889) Updated 04 Feb 2014 |
| 01 Dec 2013 | Trial Update | GlaxoSmithKline completes a phase III corticosteroid-sparing trial in Asthma in USA, Australia, Canada, France, the Czech Republic, Mexico, Germany, the Netherlands, Poland and United Kingdom (NCT01691508) Updated 15 May 2014 |
| 13 Sep 2013 | Regulatory Status | Mepolizumab - GlaxoSmithKline receives Orphan Drug status for Churg-Strauss syndrome in Japan (PMDA website, September 2013) Updated 13 Mar 2020 |
| 01 May 2013 | Trial Update | GlaxoSmithKline initiates a long-term phase III extension trial for Asthma in Argentina, Australia, Belgium, Canada, Chile, Czech Republic, France, Germany, Italy, Japan, South Korea, Mexico, Netherlands, Poland, Russia, Spain, Ukraine, USA and United Kingdom (NCT01842607; EudraCT2012-001644-21) Updated 14 May 2015 |
| 07 Feb 2013 | Phase Change - III | Phase-III clinical trials in Asthma in Romania (SC) Updated 26 Feb 2013 |
| 01 Oct 2012 | Phase Change - III | Phase-III clinical trials in Asthma in Poland (SC) Updated 15 May 2014 |
| 01 Oct 2012 | Phase Change - III | Phase-III clinical trials in Asthma in Netherlands (SC) Updated 29 Nov 2012 |
| 01 Oct 2012 | Trial Update | GlaxoSmithKline initiates enrolment in a phase III corticosteroid-sparing trial for Asthma in the US, EU, Canada and Australia (NCT01691508) Updated 29 Nov 2012 |
| 28 Sep 2012 | Trial Update | GlaxoSmithKline initiates enrolment in a long term phase III trial for Asthma in USA, Argentina, Australia, Canada, Chile, France, Germany, South Korea, Poland, Romania, Russia, Ukraine and United Kingdom (SC) (NCT01691859) Updated 01 Oct 2015 |
| 20 Aug 2012 | Phase Change - III | Phase-III clinical trials in Asthma (Adjunctive treatment, In adolescents, In adults) in Czech Republic (IV) (NCT01691521) Updated 14 May 2015 |
| 20 Aug 2012 | Phase Change - III | Phase-III clinical trials in Asthma (Adjunctive treatment, In adolescents, In adults) in South Korea, South Korea, Mexico, Japan, Chile, Canada, Australia, Argentina, United Kingdom, Ukraine, Spain, Russia, Italy, Germany, France, Belgium, USA (SC) (NCT01691521) Updated 05 Sep 2012 |
| 20 Aug 2012 | Phase Change - III | Phase-III clinical trials in Asthma (Adjunctive treatment, In adolescents, In adults) in USA, Canada, Australia, Belgium, France, Germany, Italy, Spain, Ukraine, United Kingdom, Chile, South Korea, Russia, Argentina, Mexico, Japan (IV) (NCT01691521) Updated 05 Sep 2012 |
| 01 May 2012 | Trial Update | GlaxoSmithKline completes a phase I trial for Asthma in Australia (NCT01471327) Updated 01 Oct 2015 |
| 01 Mar 2012 | Trial Update | GlaxoSmithKline completes a phase II trial for Asthma in USA, Estonia, France and Germany (NCT01366521) Updated 01 Oct 2015 |
| 29 Feb 2012 | Phase Change - No development reported(I/II) | No development reported - Phase-I/II for Eosinophilic oesophagitis in Australia, Canada, Switzerland, USA and United Kingdom (IV) Updated 05 Sep 2012 |
| 31 Jan 2012 | Phase Change - III | Phase-III clinical trials in Chronic obstructive pulmonary disease (In adults, In the elderly) in Canada (IV) (NCT01463644) Updated 14 Mar 2014 |
| 26 Jan 2012 | Trial Update | GlaxoSmithKline completes enrolment in its phase I trial in Japanese volunteers in Australia (NCT01471327) Updated 15 Feb 2012 |
| 04 Aug 2011 | Trial Update | GlaxoSmithKline completes a phase III trial in Hypereosinophilic syndrome in US, Canada, Australia, and the EU (NCT00097370) Updated 16 Aug 2011 |
| 07 Jul 2011 | Regulatory Status | Mepolizumab receives Orphan Drug status for Churg-Strauss syndrome in USA [71] Updated 05 Sep 2012 |
| 01 Feb 2011 | Phase Change - II | Phase-II clinical trials in Asthma in European Union (SC) Updated 05 Sep 2012 |
| 01 Feb 2011 | Phase Change - II | Phase-II clinical trials in Asthma in USA (SC) Updated 05 Sep 2012 |
| 01 Feb 2011 | Trial Update | GlaxoSmithKline initiates enrolment in a phase II trial for Asthma in USA, Estonia, France and Germany (NCT01366521) Updated 05 Jul 2011 |
| 01 Sep 2010 | Trial Update | GlaxoSmithKline terminates phase III trial in Hypereosinophilic syndrome in USA, Australia, Belgium, Canada, France, Germany and Italy (NCT00097370) Updated 22 Jun 2016 |
| 13 May 2010 | Phase Change - II | Phase-II clinical trials in Asthma in Russia (IV) Updated 20 May 2010 |
| 13 May 2010 | Phase Change - II | Phase-II clinical trials in Asthma in Ukraine (IV) Updated 20 May 2010 |
| 31 Mar 2010 | Phase Change - II | Phase-II clinical trials in Asthma in Chile (IV) Updated 07 Apr 2010 |
| 31 Mar 2010 | Phase Change - II | Phase-II clinical trials in Asthma in South Korea (IV) Updated 07 Apr 2010 |
| 18 Feb 2010 | Phase Change - II | Phase-II clinical trials in Asthma in Australia (IV) Updated 01 Mar 2010 |
| 18 Feb 2010 | Phase Change - II | Phase-II clinical trials in Asthma in European Union (IV) Updated 01 Mar 2010 |
| 25 Nov 2009 | Scientific Update | Pharmacodynamics, adverse events & efficacy data from the phase I/II MEE103219 trial in Paediatric eosinophilic oesophagitis presented at the GASTRO 2009 Joint Meeting (GASTRO-2009) [122] Updated 27 Nov 2009 |
| 19 Nov 2009 | Trial Update | GlaxoSmithKline initiates the phase II DREAM trial in Asthma in USA Updated 27 Nov 2009 |
| 01 Nov 2009 | Trial Update | GlaxoSmithKline completes the phase II DREAM trial for Asthma (In adolscents, In adults) in USA, Argentina, Australia, Canada, Chile, France, Germany, South Korea, Poland, Romania, Russia, Ukraine and United Kingdom (NCT01000506) Updated 01 Oct 2015 |
| 29 Jul 2009 | Phase Change - Suspended(Preregistration) | Suspended - Preregistration for Hypereosinophilic syndrome in European Union (IV) Updated 31 Jul 2009 |
| 06 May 2009 | Phase Change - II | Phase-II clinical trials in Nasal polyps in Netherlands, Belgium and United Kingdom (IV) Updated 26 May 2015 |
| 05 Sep 2008 | Phase Change - Preregistration | Preregistration for Hypereosinophilic syndrome in European Union (IV) Updated 30 Oct 2008 |
| 21 May 2008 | Scientific Update | Efficacy data from a phase II pednisone-sparing trial in asthma presented at the 104th International Conference of the American Thoracic Society (ATS-2008) [53] Updated 19 Jun 2008 |
| 25 Mar 2008 | Scientific Update | Efficacy and safety data from a phase III trial in hypereosinophilic syndrome released by GlaxoSmithKline [123] Updated 25 Mar 2008 |
| 01 Jan 2008 | Trial Update | GlaxoSmithKline completes a phase II trial in Asthma in Canada (NCT00292877) Updated 01 Oct 2015 |
| 01 Dec 2007 | Scientific Update | Efficacy data from a trial in asthma released by GlaxoSmithKline [57] Updated 03 Dec 2007 |
| 31 Oct 2007 | Scientific Update | Efficacy and adverse events data presented at the 15th United European Gastroenterology Week (UEGW-2007) [124] Updated 31 Oct 2007 |
| 02 Mar 2007 | Scientific Update | Efficacy data presented at the American Academy of Allergy, Asthma and Immunology (AAAAI-2007) [125] Updated 02 Mar 2007 |
| 31 Aug 2006 | Phase Change - I/II | Phase-I/II clinical trials in Eosinophilic oesophagitis in Canada (IV) (NCT00358449) Updated 03 Dec 2007 |
| 31 Aug 2006 | Phase Change - I/II | Phase-I/II clinical trials in Eosinophilic oesophagitis in United Kingdom (IV) (NCT00358449) Updated 03 Dec 2007 |
| 31 Aug 2006 | Phase Change - I/II | Phase-I/II clinical trials in Eosinophilic oesophagitis in USA (IV) (NCT00358449) Updated 03 Dec 2007 |
| 31 Aug 2006 | Phase Change - II | Phase-II clinical trials in Eosinophilic oesophagitis in Australia (IV) Updated 27 Dec 2006 |
| 09 Jan 2006 | Company Involvement | Protein Design Labs is now called PDL BioPharma Updated 18 Jan 2006 |
| 06 Dec 2005 | Phase Change - II | Phase-II clinical trials in Nasal polyps (IV) Updated 06 Dec 2005 |
| 01 Dec 2005 | Phase Change - I/II | Phase-I/II clinical trials in Eosinophilic oesophagitis in Switzerland (IV) Updated 29 May 2007 |
| 30 Sep 2005 | Phase Change - III | Phase-III clinical trials in Hypereosinophilic syndrome in European Union (IV) Updated 30 Oct 2008 |
| 30 Sep 2005 | Phase Change - III | Phase-III clinical trials in Hypereosinophilic syndrome in Switzerland (IV) Updated 30 Oct 2008 |
| 28 Feb 2005 | Active Status Review | This compound is still in active development for Asthma Updated 14 Sep 2005 |
| 01 Jan 2005 | Phase Change - II | Phase-II clinical trials in Asthma in Canada (IV) Updated 29 May 2007 |
| 01 Dec 2004 | Phase Change - III | Phase-III clinical trials in Hypereosinophilic syndrome in USA (IV) Updated 27 Dec 2006 |
| 01 Dec 2004 | Phase Change - III | Phase-III clinical trials in Hypereosinophilic syndrome in USA (IV) Updated 01 Dec 2004 |
| 30 Sep 2004 | Phase Change - III | Phase-III clinical trials in Hypereosinophilic syndrome in Australia (IV) Updated 30 Oct 2008 |
| 30 Sep 2004 | Phase Change - III | Phase-III clinical trials in Hypereosinophilic syndrome in France (IV) Updated 30 Oct 2008 |
| 30 Sep 2004 | Phase Change - III | Phase-III clinical trials in Hypereosinophilic syndrome in Germany (IV) Updated 30 Oct 2008 |
| 30 Sep 2004 | Phase Change - III | Phase-III clinical trials in Hypereosinophilic syndrome in Italy (IV) Updated 30 Oct 2008 |
| 01 Sep 2004 | Trial Update | GlaxoSmithKline initiates enrolment in a phase III extension trial in Hypereosinophilic syndrome in USA, Australia, Belgium, Canada, France, Germany and Italy (NCT00097370) Updated 22 Jun 2016 |
| 29 Jul 2004 | Regulatory Status | Mepolizumab receives Orphan Drug status for Hypereosinophilic syndrome in European Union Updated 29 May 2007 |
| 28 May 2004 | Phase Change | Mepolizumab receives Orphan Drug Status for Hypereosinophilic syndrome in USA Updated 21 Apr 2005 |
| 31 Mar 2004 | Phase Change - II | Phase-II clinical trials in Hypereosinophilic syndrome in Australia (IV) Updated 30 Oct 2008 |
| 31 Mar 2004 | Phase Change - II | Phase-II clinical trials in Hypereosinophilic syndrome in France (IV) Updated 30 Oct 2008 |
| 31 Mar 2004 | Phase Change - II | Phase-II clinical trials in Hypereosinophilic syndrome in Germany (IV) Updated 30 Oct 2008 |
| 31 Mar 2004 | Phase Change - II | Phase-II clinical trials in Hypereosinophilic syndrome in Italy (IV) Updated 30 Oct 2008 |
| 31 Mar 2004 | Phase Change - II | Phase-II clinical trials in Hypereosinophilic syndrome in Switzerland (IV) Updated 30 Oct 2008 |
| 30 Mar 2004 | Phase Change - III | Phase-III clinical trials in Eosinophilia in Canada (IV) Updated 29 May 2007 |
| 08 Mar 2004 | Scientific Update | A study has been added to the Haematological Disorders therapeutic trials section [126] Updated 08 Mar 2004 |
| 05 Jan 2004 | Scientific Update | A study has been added to the Haematological Disorders therapeutic trials section [127] Updated 05 Jan 2004 |
| 29 Dec 2003 | Phase Change - II | Phase-II clinical trials in Hypereosinophilic syndrome in USA (IV) Updated 29 Dec 2003 |
| 19 Mar 2003 | Scientific Update | Data presented at the 60th Anniversary Meeting of the American Academy of Allergy and Asthma and Immunology (AAAAI-2003) have been added to the Obstructive Airways Disease and Haematological Disorders pharmacodynamics sections [128] , [129] Updated 19 Mar 2003 |
| 12 Aug 2002 | Scientific Update | A clinical study has been added to the Obstructive Airways Disease pharmacodynamics section [130] Updated 12 Aug 2002 |
| 21 May 2002 | Phase Change - II | Phase-II clinical trials in Atopic dermatitis in USA (IV) Updated 21 May 2002 |
| 23 Jan 2001 | Company Involvement | SmithKline Beecham has merged with Glaxo Wellcome to form GlaxoSmithKline Updated 23 Jan 2001 |
| 23 Jan 2001 | Scientific Update | A study in patients with allergic asthma has been added to the Obstructive Airways Disease pharmacodynamics section [131] Updated 23 Jan 2001 |
| 04 May 1999 | Scientific Update | A study in asthmatic patients has been added to the pharmacokinetics and the Obstructive Airways Disease pharmacodynamics sections [132] Updated 04 May 1999 |
| 03 Jun 1998 | Phase Change - II | Phase-II clinical trials for Asthma in USA (IV) Updated 03 Jun 1998 |
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Mepolizumab- ODD. Internet-Doc 2020;.
Available from: URL: https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=345111 -
EMA approval - Nucala (mepolizumab). Internet-Doc 2023;.
Available from: URL: https://www.ema.europa.eu/en/documents/overview/nucala-epar-medicine-overview_en.pdf -
GSK Nucala (mepolizumab) filings accepted by European Medicines Agency for three additional eosinophil-driven diseases.
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Pfizer 6-K July 2018. Internet-Doc 2018;.
Available from: URL: https://otp.investis.com/clients/us/gskqc/SEC/sec-show.aspx?FilingId=12872987&Cik=0001131399&Type=PDF&hasPdf=1 -
Pfizer 6-K September 2018. Internet-Doc 2018;.
Available from: URL: https://otp.investis.com/clients/us/gskqc/SEC/sec-show.aspx?FilingId=12956035&Cik=0001131399&Type=PDF&hasPdf=1 -
Mepolizumab Long-term Access Programme for Subjects who Participated in Study MEA115921 (Placebo-controlled Study of Mepolizumab in the Treatment of Eosinophilic Granulomatosis with Polyangiitis in Subjects Receiving Standard-of-care Therapy)
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Khoury P, Silver J, Wolff G, Verghis R, Wechsler M. Long-Term Safety of Mepolizumab in EGPA: Results From the Long-Term Access Programme. AAAAI-2024 2024; abstr. L35.
Available from: URL: https://annualmeeting.aaaai.org/ -
GSK announces phase lll study of mepolizumab meets co-primary endpoints and all secondary endpoints in patients with eosinophilic granulomatosis with polyangiitis.
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A Double-blind, Randomised, Placebo-controlled Study to Investigate the Efficacy and Safety of Mepolizumab in the Treatment of Eosinophilic Granulomatosis With Polyangiitis in Subjects Receiving Standard of Care Therapy
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GSK announces NEJM publication of positive phase III study investigating mepolizumab in patients with Eosinophilic Granulomatosis with Polyangiitis (EGPA).
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Khoury P, Makiya M, Dyer A-M, Akuthota P, Bochner BS, Chinchilli VM, et al. Urine eosinophil-derived neurotoxin declines following mepolizumab treatment in subjects with Eosinophilic Granulomatosis with Polyangiitis. AAAAI-2019 2019; abstr. 877.
Available from: URL: http://link.adisinsight.com/k6Q5L -
NUCALA (mepolizumab) approved in Canada as the first and only biologic treatment for adults with hypereosinophilic syndrome.
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FDA Approves Nucala as the First and Only Biologic Treatment for Hypereosinophilic Syndrome (HES).
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FDA Approves First Drug to Treat Group of Rare Blood Disorders in Nearly 14 Years.
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Regulatory update: mepolizumab for the treatment of hypereosinophilic syndrome (HES).
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A Phase 3, 52-week, Open-label, Single Arm Study to Investigate the Efficacy and Safety of Mepolizumab SC in Participants Aged 6 to 17 Years With Hypereosinophilic Syndrome
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Roufosse F, Steinfeld J, Gleich GJ, Chupp G, Faguer S, Reiter A, et al. Safety and Efficacy of Mepolizumab in Hypereosinophilic Syndrome: an Open-Label Extension Study. EHA-2021 2021; abstr. EP1087.
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Steinfeld J, Gleich GJ, Roufosse F, Chupp G, Faguer S, Reiter A, et al. Safety and Efficacy of Mepolizumab in Hypereosinophilic Syndrome: An Open-Label Extension Study. ATS-2021 2021; abstr. A1351.
Available from: URL: https://conference.thoracic.org/program/abstract-search.php?sid=P8560 -
A multi-centre, open-label extension, safety study to describe the longterm clinical experience of mepolizumab in participants with hypereosinophilic syndrome (HES) from Study 200622
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104317: An Open-Label Compassionate Use Access and Long-Term Access Study of Anti IL-5 (Mepolizumab) Treatment in Subjects With Hypereosinophilic Syndrome. 201956: A Long-term Access Programme for Subjects With Severe Asthma Who Participated in a GSK-sponsored Mepolizumab Clinical Study. 112562: Expanded Access to Mepolizumab for Patients With Hypereosinophilic Syndrome
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Steinfeld J, Rofousse F, Kahn J, Gleich G, Rothenberg M, Wardlaw A, et al. Efficacy and Safety of Mepolizumab in Hypereosinophilic Syndrome: A Phase III, Randomized, Placebo-Controlled Trial. ATS-2020 2020; abstr. N/A.
Available from: URL: http://link.adisinsight.com/p8F2R -
Nucala (mepolizumab) is the first treatment to show a significant reduction in flares for patients with Hypereosinophilic Syndrome (HES).
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GSK starts phase III study with mepolizumab in patients with severe hypereosinophilic syndrome.
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Study 200622: A Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy and Safety of Mepolizumab in the Treatment of Adolescent and Adult Subjects With Severe Hypereosinophilic Syndrome
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Roufosse F, Butter?eld J, von Maltzahn R, Nelsen L, Bentley J, Kwon N, et al. Impact of mepolizumab on symptom severity in patients with hypereosinophilic syndrome. AAAAI-2021 2021; abstr. 446.
Available from: URL: https://annualmeeting.aaaai.org/ -
Pane F, Lefevre G, Kwon N, Bentley JH, Yancey SW, Steinfeld J. Impact of Mepolizumab on Disease Flares in Patients with Hypereosinophilic Syndrome. ATS-2021 2021; abstr. A1809.
Available from: URL: https://conference.thoracic.org/program/abstract-search.php?sid=P5516 -
A Multicenter, Double-blind, Placebo-controlled, Study to to Evaluate the Corticosteroid- Sparing Effects of Mepolizumab in Subjects With Hypereosinophilic Syndromes (HES) and Evaluate Efficacy and Safety of Mepolizumab in Controlling the Clinical Signs and Symptoms of Subjects With HES
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An Open Label Extension Study to Evaluate Safety and Efficacy of Mepolizumab in Patients With Hypereosinophilic Syndromes.
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GSK announces FDA approval for Nucala (mepolizumab) for use in adults with chronic rhinosinusitis with nasal polyps.
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FDA accepts GSK's filing of Nucala (mepolizumab) for use in chronic rhinosinusitis with nasal polyps.
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NUCALA (mepolizumab) the first and only anti-IL-5 add-on treatment approved in Canada that targets eosinophilic inflammation in adults with chronic rhinosinusitis with nasal polyps (CRSwNP).
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A Randomised, Double-blind, Placebo Controlled, Parallel Group Phase III Study to Assess the Clinical Efficacy and Safety of 100 mg SC Mepolizumab in Adults With Chronic Rhinosinusitis With Nasal Polyps (CRSwNP) / Eosinophilic Chronic Rhinosinusitis (ECRS) MERIT: Mepolizumab in Eosinophilic Chronic RhinosinusITis Study
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Hopkins C, Han JK, Lund VJ, Bachert C, Diamant Z, Fokkens W, et al. Late Breaking Abstract - Response to mepolizumab in patients with severe CRSwNP using EUFOREA 2021 criteria. ERS-2021 2021; abstr. N/A.
Available from: URL: https://erj.ersjournals.com/content/58/suppl_65/PA3536 -
Chupp GL, Alobid I, Lugogo N, Kariyawasam HH, Bourdin A, Chaker AM, et al. Mepolizumab Reduces Systemic Corticosteroid Use in Patients with Chronic Rhinosinusitis with Nasal Polyps. ATS-2021 2021; abstr. A1344.
Available from: URL: https://conference.thoracic.org/program/abstract-search.php?sid=P6073 -
Lee S, Tabberer M, Trigg A, Han J, Fokkens W, Naclerio R, et al. Mepolizumab Improves Health Related Quality of Life for Patients with Chronic Rhinosinusitis with Nasal Polyps: Data from the SYNAPSE study. AAAAI-2021 2021; abstr. 399.
Available from: URL: https://annualmeeting.aaaai.org/ -
Tabberer M, Trigg A, Busse W, Lund V, Lee J, Bachert C, et al. Mepolizumab reduces disease symptoms for Patients with Chronic Rhinosinusitis with Nasal Polyps: Data from the SYNAPSE study. AAAAI-2021 2021; abstr. 402.
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Bachert C, Sousa A, Han J, Schlosser R, Sowerby L, Hopkins C, et al. Mepolizumab for Chronic Rhinosinusitis with Nasal Polyps: Comorbid Asthma, Nsaid Exacerbated Respiratory Disease, Eosinophil Stratification. ACAAI-2020 2020; abstr. P503.
Available from: URL: https://www.sciencedirect.com/science/article/pii/S1081120620307304 -
GSK starts phase III study with mepolizumab in patients with nasal polyps.
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Nucala (mepolizumab) is the first anti-IL5 biologic to report positive phase 3 results in patients with nasal polyps.
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A Randomised, Double-blind, Parallel Group PhIII Study to Assess the Clinical Efficacy and Safety of 100 mg SC Mepolizumab as an Add on to Maintenance Treatment in Adults With Severe Bilateral Nasal Polyps - SYNAPSE (StudY in NAsal Polyps Patients to Assess the Safety and Efficacy of Mepolizumab)
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Mullol J, Lund V, Wagenmann M, Han J, Sousa A, Smith S, et al. Mepolizumab Induced Loss of Smell Improvement in Patients With Chronic Rhinosinusitis With Nasal Polyps From the SYNAPSE Study. AAAAI-2022 2022; abstr. 481.
Available from: URL: https://annualmeeting.aaaai.org/ -
Luong A, Levy J, Klimek L, Harvey R-c, Silver J, Smith S, et al. Change in nasal polyp size as an indicator of treatment response: SYNAPSE trial analysis. AAAAI-2023 2023; abstr. 336.
Available from: URL: https://annualmeeting.aaaai.org/ -
Profiling Symptomatic and Quality of Life Benefits of Mepolizumab for Patients With Chronic Rhinosinusitis With Nasal Polyps (CRSwNP) in the SYNAPSE Trial. AAAAI-2024 2024;.
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A Randomised PhIII study to assess the effect of 100 mg SC Mepolizumab in the nasal polyp score and symptoms in subjects with bilateral Nasal polyps (NP) and in current need of NP surgery
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A Randomised, Double-Blind, Placebo Controlled, Multi-Center Study To Investigate The Use Of Mepolizumab (Sb-240563) In Reducing The Need For Surgery In Subjects With Severe Bilateral Nasal Polyposis
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A Multi-center, Randomized, Double Blind, Parallel-arm, Placebo Controlled Trial of Mepolizumab for Treatment of Adults and Adolescents With Active Eosinophilic Esophagitis and Dysphagia-predominant Symptoms
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Study 205050: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Investigate the Efficacy and Safety of Mepolizumab Administered Subcutaneously in Subjects With Moderate to Severe Atopic Dermatitis
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GSK delivers strong Q1: sales Lstg9.1 billion +19% AER, +19% CER (Proforma +10% CER*).
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GSK's MUSCA study shows Nucala(Rm) (mepolizumab) significantly improves quality of life and lung function in severe asthma patients with an eosinophilic phenotype.
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GSK presents data at AAAAI on efficacy of Nucala(R) (mepolizumab) in severe asthma patients stratified by eosinophil levels.
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Cockle S, Nelsen L, Kimel M, Albers FC, Jones P. Impact of Asthma Exacerbations on Health Status in Patients with Severe Asthma. AAAAI-2016 2016; abstr. 23.
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Thomson M. Safety and Pharmacodynamics of Mepolizumab, a Humanised Monoclonal Antibody Against Il-5, in Paediatric Subjects with Eosinophilic Oesophagitis: a Randomised, Double-blind, Controlled Clinical Trial. 2009-UEGW-WCOG 2009; abstr. OP002.
Available from: URL: http://www.gastro2009.org -
Phase III study of Bosatria (mepolizumab) showed disease control with reduced corticosteroid use in hypereosinophilic syndrome.
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Straumann A, Conus S, Kita H, Gail K, Bussmann C, Beglinger C, et al. Mepolizumab, a humanized monoclonal antibody to IL-5, for severe eosinophilic esophagitis in adults: a randomized, placebo-controlled double-blind trial. Gut 2007;56 (Suppl. 3)7.
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Weller PF, Gleich GJ, Busse WW, Rothenberg ME, Mepolizumab HES Study. Effects of mepolizumab, an anti-interleukin-5 monoclonal antibody, on blood eosinophil counts in patients with hypereosinophilic syndrome. J-Allergy-Clin-Immunol 2007;119 (Suppl.)(1):209.
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Garrett JK, Jameson SC, Thomson B, Collins MH, Wagoner LE, et al. Anti-interleukin-5 (mepolizumab) therapy for hypereosinophilic syndromes. J-Allergy-Clin-Immunol 2004;113(1):115-119.
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Phipps S, Flood-Page P, Menzies-Gow A, Wangoo A, Barnes N, et al. Anti-IL-5 (mepolizumab) reduces the expression of tenascin, procollagen III and lumican in the reticular basement membrane of human atopic asthmatics. J-Allergy-Clin-Immunol 2003;111 (Suppl.)278 (plus oral presentation).
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Flood-Page P, Phipps S, Menzies-Gow A, Ong Y, Kay AB. Effect of intravenous administration of an anti-IL-5 mAb (mepolizumab) on allergen-induced tissue eosinophilia, the late-phase allergic reaction and the expression of a marker of repair/remodeling in human atopic subjects. J-Allergy-Clin-Immunol 2003;111 (Suppl.)261 (plus poster).
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Nucala (mepolizumab) improved asthma control in patients uncontrolled on Xolair (omalizumab).
Media Release
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