Reslizumab - Teva Pharmaceuticals
Alternative Names: Anti-interleukin-5-monoclonal antibody-Celltech/Schering-Plough; CDP-835; CEP-38072; CINQAERO; CINQAIR; Cinquil; CTx-55700; DCP-835; SCH 55700; TRFK-5Latest Information Update: 06 Jun 2023
At a glance
- Originator Celltech R&D; Schering-Plough
- Developer Allergy and Asthma Clinical Research; Celltech R&D; Teva Pharmaceutical Industries
- Class Antiasthmatics; Monoclonal antibodies
- Mechanism of Action Interleukin 5 inhibitors
-
Orphan Drug Status
Yes - Oesophagitis
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
- Phase III Sinusitis
- Phase II Churg-Strauss syndrome
- No development reported Oesophagitis
Most Recent Events
- 06 Feb 2023 Launched for Asthma in Austria, Greece, Belgium, Finland, Spain, Denmark, Sweden, Portugal, Czech Republic, Netherlands, Poland, Hungary, United Kingdom, Russia, Norway (IV) prior to February 2023
- 19 Feb 2021 Discontinued - Phase-III for Asthma (In adolescents, In the elderly, Treatment-experienced, In adults) in New Zealand, Poland, Belgium, Russia, Australia, Hungary, South Africa, Spain, Ukraine, Argentina, France, Germany, Czech Republic, Israel, Italy, Mexico, South Korea, Canada, Netherlands, Japan, Turkey, Romania, USA (SC) (Teva Pharmaceuticals pipeline, February 2021)
- 10 Feb 2021 National Jewish Health completes a phase II trial in Churg-Strauss syndrome in USA (IV) (NCT02947945)
Development Overview
Introduction
Reslizumab, an anti-interleukin-5 monoclonal antibody, is being developed by Teva, for the treatment of eosinophilic asthma, Churg-strauss syndrome and eosinophilic oesophagitis. Interleukin-5 (IL-5) stimulates the production, activation and maturation of eosinophils and is therefore thought to play a role in the development of bronchial hyper-responsiveness and eosinophilia. The anti-IL-5 antibody identified by Celltech was initially developed against murine IL-5 and was known as TRFK-5. A humanised form of the antibody was developed when TRFK-5 was shown to also neutralise human IL-5. Intravenous reslizumab is launched in several countries for the treatment of asthma. Clinical development of IV formulations for asthma, sinusitis and Churg-strauss syndrome is underway in several countries.
As of February 2021, development of SC formulation of reslizumab for the treatment of asthma in patients 12 years and older was discontinued (Teva Pharmaceuticals pipeline, February 2021)
Reslizumab was under phase III development for eosinophilic oesophagitis, however no recent reports have been identified. An intranasal formulation was also undergoing preclinical studies in the US. However, development of this product also appears to have been discontinued.
Reslizumab was initially being developed by Celltech and Schering-Plough (now Merck & Co., Inc.). However, development was discontinued by Schering-Plough and the agent was subsequently licensed to Ception Therapeutics. Ception was acquired by Cephalon in 2010, and Cephalon was subsequently acquired by Teva in October 2011. Celltech Group was acquired by UCB in April 2005 [1] [2] .
Company Agreements
In January 2009, Ception and Cephalon signed an agreement providing Cephalon with an option to acquire Ception [3] . Following the announcement in November 2009 that the phase IIb/III Res-05-0002 trial in eosinophilic oesophagitis did not meet one of its co-primary endpoints, the parties agreed to extend Cephalon′s option exercise period until a specified period of time after delivery of the top-line results for the phase II Res-5-0010 trial in eosinophilic asthma [4] . In April 2010, Cephalon completed the acquisition of Ception Therapeutics [5] .
Key Development Milestones
Eosinophilic asthma (IV infusion)
As of February 2023, reslizumab is available for Asthma in Austria, Belgium, Canada, Czech Republic, Denmark, Finland, Greece, Hungary, Israel, Netherlands, Norway, Poland, Portugal, Russia, Spain, Sweden, USA and the UK [6]
In November 2017, The Scottish Medicines Consortium rejected reslizumab for routine use by NHS Scotland for the treatment of eosinophilic asthma. The committee was unable to accept reslizumab as it was not satisfied about its cost effectiveness in relation to other similar preparations [7] .
In July 2017, the National Institute for Helth and Care Excellence (NICE) recommended CINQAERO® (reslizumab) in its Final Appraisal Determination (FAD), which is based on a dossier submitted to NICE for a Single Technology Appraisal [8] .
In June 2016, Teva launched reslizumab, for the treatment of asthma in the US. In March 2016, the US FDA approved reslizumab for the add-on maintenance treatment of asthma in adults with elevated levels of eosinophils [9] [10] . In December 2015, the US FDA's Pulmonary-Allergy Drugs Advisory Committee recommended approval of reslizumab for the treatment of inadequately controlled asthma in adult patients with elevated blood eosinophils, despite an inhaled corticosteroid based treatment regimen. In June 2015, Teva submitted a Biologics License Application with the US FDA seeking approval of reslizumab for the treatment of asthma in adults and adolescents with elevated levels of eosinophils, who were previously treated with inhaled corticosteroid-based regimen. The company expects to launch reslizumab during the second quarter of 2016 [11] [12] .
In July 2016, Health Canada has approved reslizumab for the add-on maintenance treatment of asthma in adults with elevated levels of eosinophils [13] . In December 2015, Teva reported that reslizumab was submitted and was under review by the Health Canada [11] .
In August 2016, reslizumab was granted marketing authorisation by the European Commission, for the treatment of asthma [14] . In June 2016, the Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion for Teva's MAA for the approval of reslizumab in the treatment of asthma [15] . Teva filed a Marketing Authorization Application with the European Medicines Agency (EMA) in July 2015, seeking approval of reslizumab for the treatment of asthma in adults with elevated levels of eosinophils, who were previously treated with inhaled corticosteroid-based regimen [16] . The application is based on the phase III trial programme. The company expects a final decision from the EMA in the second half of 2016 [17] .
In July 2017, Therapeutic Goods Administration of Australia approved reslizumab, for the treatment of severe eosinophilic asthma patients with blood eosinophil count greater than or equal to 400 cells/μl [18] .
In July 2017, the German Federal Joint Committee issued a positive additional medical benefit opinion for reslizumab in patients with severe eosinophilic asthma, who were treated regularly with corticosteroids in addition to the treatment for acute exacerbations, thereby allowing Teva to initiate reimbursement related discussions with the National Association of Statutory Health Insurance Physicians in Germany. The committee's decision was based on data from two pivotal phase III studies, including study 3082 and study 3083 [19] .
In March 2017, Teva completed a phase III trial designed to assess the safety and tolerability of intravenously administered reslizumab in patients with eosinophilic asthma who were enrolled in open-label extension study C38072/3085 (see below) (EudraCT2014-002659-25). The open label trial initiated in July 2016 enrolled 10 patients in France [20] .
In May 2014, Teva completed a phase III trial, which investigated the safety and efficacy of reslizumab (3 mg/kg every 4 weeks) in reducing clinical eosinophilic asthma exacerbations in patients aged 12 to 75 years (C38072/3083; EudraCT2010-024006-35; NCT01285323). The randomised, double-blind, placebo-controlled trial was initiated in March 2011 and enrolled 464 patients in the US, Argentina, Brazil, Canada, France, Germany, Greece, South Korea, Mexico, Peru, Romania, Russia, Slovakia, Taiwan and Ukraine [21] . In March 2011, Cephalon initiated a second, 12-month, randomised, double-blind, placebo-controlled phase III trial to assess the safety and efficacy of reslizumab (3 mg/kg every 4 weeks) in reducing clinical eosinophilic asthma exacerbations in patients aged 12 to 75 years (C38072/3082; NCT01287039). The trial enrolled 489 patients in the US, australia, Belgium, Chile, Colombia, Czech Republic, Denmark, Hungary, India, Israel, Malaysia, New Zealand, Philippines, Poland, Russia, South Africa, Sweden and Thailand, and was completed in April 2014 [22] . In September 2014, Teva reported positive results and announced that the primary endpoint was met in both the trials. Based on the positive results from these two trials, the company plans for regulatory submissions in the US, followed by the EU and other regions, in the first half of 2015 [23] [24] . In September 2015, Teva presented results from a post hoc analysis of two phase III trials at the 25th Annual Congress of the European Respiratory Society (ERS-2015), which demonstrated that reslizumab reduced clinical asthma exacerbations by 75% in patients with late onset asthma and elevated blood eosinophil levels [25] . The Lancet Respiratory Medicine published positive data from these two global phase III trials in February 2015. Treatment with reslizumab compared with placebo significantly reduced the annual rate of clinical asthma exacerbations, improved ling function and maintained improvement in eosinophilic asthma exacerbations [23] . Pooled results from the two duplicate 52-week trials (BREATH programme) of reslizumab in patients with inadequately controlled asthma and blood eosinophils ≥400cells/μL, were presented by the company at the 2016 Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI-2016) in March 2016 [26] . Updated pooled results were presented at the 2017 Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI-2017) in March 2017. In March 2018, the company presented additional data from the trial at the 2018 Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI-2018) [27] [28] .
Reslizumab initiated a phase III trial of reslizumab for the treatment of eosinophilic asthma, in January 2011. The randomised, double-blind phase III BREATH trial (NCT01270464; EudraCT2010-023342-67) evaluated reslizumab compared with placebo in patients with eosinophilic asthma over a 16-week period. Approximately 315 patients aged 12 to 75 years were recruited in the US, Canada, Argentina, Brazil, France, Colombia, Mexico, Poland, Israel, Belgium, Hungary, Netherlands and Sweden. The trial was completed in January 2014 [29] [30] .
A US-based phase III trial, enrolled 510 patients with moderate-to-severe asthma and was completed in October 2013 (C38072/3084; NCT01508936). This study was initiated in January 2012 and investigated efficacy of reslizumab (3 mg/kg, every 4 weeks) over 16 weeks in patients already taking fluticasone (>440 µg/day) [31] . Results from this study showed minimal improvements in asthma control, and supported the eosinophil threshold of = 400 /µL established for the reslizumab phase III programme [29] .
A phase III extension trial evaluating the long-term safety of reslizumab (3.0 mg/kg every 4 weeks) was terminated in February 2015 due to a business purpose. This open-label study was conducted in 1052 patients aged 12 to 75 years with eosinophilic asthma (C38072/3085; EudraCT2010-024540-15; NCT01290887). The study was initiated in June 2011 and was designed to recruit patients at centres throughout the world [32] .
In October 2015, McMaster University, in collaboration with Teva Pharmaceuticals and St. Joseph's Healthcare Hamilton, initiated a phase II/III trial to assess the efficacy of four monthly IV doses of reslizumab 3 mg/kg in prednisone-dependent patients with eosinophilic asthma (RES-38072; NCT02559791). The primary endpoint will determine the changes in sputum eosinophil percentage and blood eosinophil absolute number measured before the placebo phase (week 2), after 2 infusions of placebo (week 10), and after 4 infusions/4 months (week 26) of reslizumab. The single-blind, placebo-controlled trial will recruit 15 patients (aged 18 - 75 years), by invitation only, in Canada [33] .
A phase II trial (Res-5-0010; NCT00587288) of intravenous reslizumab in patients with poorly controlled, eosinophilic asthma was initiated by Ception in November 2007. Patients received reslizumab 3mg/kg or placebo every 28 days, for a total of four treatment cycles. The primary aim was to determine the safety and efficacy of the agent, as measured by an asthma control questionnaire at 15 weeks. The trial enrolled 106 patients aged 18 to 75 years in the US and Canada, and was completed in August 2010 [34] [4] .
Phase II dose-ranging trials of intravenous reslizumab were previously being conducted by Schering-Plough for the treatment of asthma. The trials were evaluating administration of reslizumab once every three months, and were being conducted at several centres worldwide, in countries including Belgium and the US. However, development of reslizumab was discontinued by Schering-Plough [1] .
Teva completed a randomised phase I trial in March 2014, that assessed the absolute bioavailability of reslizumab following a single subcutaneous dose, compared to intravenous administration, in healthy volunteers (C38072/1107; NCT01990443). The trial was initiated in June 2013 and enrolled 75 subjects in the US [35] .
Subcutaneous formulation
Subcutaneous formulation of reslizumab was being developed for the treatment of asthma. However, as of February 2021, development has been discontinued for the same (Teva Pharmaceuticals pipeline, February 2021).
In January 2018, Teva reported that the completed phase III trial did not meet its primary endpoint of significantly reducing the frequency of clinical asthma exacerbations (CAEs) in patients with uncontrolled asthma and elevated blood eosinophils > 300/mcL. Teva completed the 52-week phase III trial that assessed the efficacy and safety of reslizumab 110 mg administered subcutaneously every 4 weeks in adults and adolescents (≥ 12 years) with asthma and elevated blood eosinophils who are inadequately controlled on standard-of-care therapy in September 2015 (C38072-AS-30025; NCT02452190; EudraCT2015-000865-29; P017-2015; P256-2016). The randomised, double-blind, placebo-controlled trial enrolled 469 patients in the US, Australia, Argentina, Belgium, Canada, Japan, Turkey, Romania, New Zealand, Poland, Russia, South Africa, Ukraine, Czech Republic, Hungary, Spain, France, Germany, Israel, Italy, South Korea, Mexico and the Netherlands. The company released topline results showing that a pre-specified a priori-powered subgroup analysis of 80% of the total randomised severe asthma patient population with baseline blood eosinophil count of = 400/mcL showed significant reduction in CAE risk (p <0.025) with no safety concerns and no cases of anaphylaxis [36] [37] .
In January 2018, Teva reported that the phase III trial did not meet its primary endpoint of significantly reducing the frequency of clinical asthma exacerbations (CAEs) in patients with uncontrolled asthma and elevated blood eosinophils >300/mcL. In December 2017, Teva completed a phase III trial that evaluated the efficacy and safety of subcutaneous reslizumab, in patients with oral corticosteroid-dependent asthma and elevated blood eosinophils (C38072-AS-30027; EudraCT2015-001580-39; NCT02501629). Evaluation of the percent reduction in daily OCS dose was the primary endpoint of the trial. The randomised, double blind, placebo controlled trial was initiated in September 2015, and enrolled 177 patients in the US, Australia, Czech Republic, Poland, Argentina, Belgium, France, Germany, Hungary, Israel, Italy, Mexico, South Korea, the Netherlands, Russia, Spain, Ukrain. The company released topline results showing that a pre-specified a priori-powered subgroup analysis of 80% of the total randomised severe asthma patient population with baseline blood eosinophil count of = 400/mcL showed significant reduction in CAE risk (p <0.025) with no safety concerns and no cases of anaphylaxis [36] [38] .
In February 2018, Teva Pharmaceutical terminated an open-label extension phase III trial as the parent studies didn't meet their primary endpoint. The trial was designed to obtain additional long-term safety data for subcutaneous administration of reslizumab treatment, administered at a fixed dose of 110mg, in patients with severe eosinophilic asthma who completed the treatment period of a placebo-controlled phase III trial of SC reslizumab (C38072-AS-30066; EudraCT2016-004661-23; NCT03052725). The trial was initiated in March 2017, and enrolled 391 patients (aged 12 years and older) in the US, Belgium, Czech Republic, Hungary, Germany, France, Spain, Poland, Canada, Israel, Romania, Russia and Ukraine [39] .
Sinusitis
Allergy and Asthma Clinical Research initiated a phase III trial to investigate whether reslizumab is effective for the treatment of patients with chronic sinusitis (NCT02799446; AACR-01). The double-blind, randomised trial will enrol approximately 30 participants in the US [40] .
Intranasal formulation
An intranasal formulation of TRFK-5 was also undergoing preclinical studies in the US. However, development of this product also appears to have been discontinued [41] [42] .
Eosinophilic Granulomatosis With Polyangiitis (Churg-Strauss syndrome in the development table)
In February 2021, Teva Pharmaceuticals in collaboration with National Jewish Health completed a phase II trial that evaluated the efficacy and safety of reslizumab in the treatment of Eosinophilic Granulomatosis With Polyangiitis (EGPA) Study (NCT02947945; HS3025). The open label trial was initiated in September 2017, and enrolled 10 patients in the US [43] .
Eosinophilic oesophagitis
Teva was developing intravenous reslizumab for the treatment of eosinophilic oesophagitis. However, no recent reports on development for eosinophilic oesophagitis were identified (Teva pipeline, May 2015).
In October 2009, Ception completed a 4-month phase IIb/III trial (Res-05-0002; NCT00538434) of intravenous reslizumab in 226 paediatric and adolescent patients (aged 5 to 18 years) with eosinophilic oesophagitis, in the US and Canada. Oesophageal eosinophil counts and an eosinophilic oesophagitis global assessment scale were used to evaluate 1, 2 and 3 mg/kg doses of reslizumab versus placebo. A child health questionnaire and oesophageal eosinophil symptom assessment were used as secondary outcome measures. Interim results showed that the trial did not meet one of its co-primary endpoints. The company stated it would continue to analyse the data from this trial and the Res-5-0004 extension trial to determine the path forward for the development of reslizumab in this indication [4] [44] [45] .
In May 2008, Ception initiated an open-label, phase III extension trial (Res-5-0004; NCT00635089), which enrolled patients who had completed the Res-05-0002 trial. This trial assessed the long term safety and efficacy of reslizumab in paediatric and adolescent patients with eosinophilic oesophagitis. The trial was completed in January 2012 and enrolled 190 patients in the US and Canada [46] .
The US FDA granted orphan drug status to reslizumab for the treatment of eosinophilic oesophagitis [44] .
Patent Information
Teva has patent exclusivity for reslizumab in the US and the EU until 2017 and 2015, respectively. The company expects ten years of regulatory exclusivity in the EU and twelve years of biological exclusivity in the US, starting from the approval date of reslizumab (Teva 20-F, February 2015).
Drug Properties & Chemical Synopsis
- Route of administration Intranasal, IV, Parenteral, SC
- Formulation Infusion, Injection, unspecified
- Class Antiasthmatics, Monoclonal antibodies
- Target Interleukin 5
- Mechanism of Action Interleukin 5 inhibitors
-
WHO ATC code
R03D (Other Systemic Drugs for Obstructive Airway Diseases)
-
EPhMRA code
R3X2 (All other anti-asthma and COPD products, systemic)
- Chemical name Immunoglobulin G4 (human-rat monoclonal SCH 55700 γ4-chain anti-human interleukin 5), disulfide with human-rat monoclonal SCH 55700 light chain, dimer
- CAS Registry Number 241473-69-8
Biomarkers Sourced From Trials
| Indication | Biomarker Function | Biomarker Name | Number of Trials |
|---|---|---|---|
|
asthma |
Outcome Measure |
Uric acid T-cell surface antigen CD4 T-Cell differentiation antigen CD8 LOC102724197 L-Aspartic acid immunoglobulin heavy constant epsilon Hematopoietic progenitor cell antigen CD34 GGTLC5P GGTLC4P GGT gamma-glutamyltransferase light chain 3 gamma-glutamyltransferase light chain 1 gamma-glutamyltransferase 2 Fc fragment of IgG receptor Ib ALT alpha-1 antitrypsin (SERPINA1) |
|
|
asthma |
Brief Title |
Interleukin-5 (IL-5) |
|
|
asthma |
Detailed Description |
T-cell surface antigen CD4 T-Cell differentiation antigen CD8 Hematopoietic progenitor cell antigen CD34 Fc fragment of IgG receptor Ib |
|
|
asthma |
Eligibility Criteria |
filamin C, gamma COPD |
|
|
asthma |
Official Title |
Interleukin-5 (IL-5) |
|
|
asthma |
Brief Summary |
T-cell surface antigen CD4 T-Cell differentiation antigen CD8 Hematopoietic progenitor cell antigen CD34 Fc fragment of IgG receptor Ib |
|
|
atopic dermatitis |
Brief Title |
Interleukin-5 (IL-5) |
|
|
atopic dermatitis |
Official Title |
Interleukin-5 (IL-5) |
|
|
chronic obstructive pulmonary disease |
Brief Title |
Interleukin-5 (IL-5) |
|
|
chronic obstructive pulmonary disease |
Official Title |
Interleukin-5 (IL-5) |
|
|
Churg-Strauss syndrome |
Brief Title |
Interleukin-5 (IL-5) |
|
|
Churg-Strauss syndrome |
Official Title |
Interleukin-5 (IL-5) |
|
|
eosinophilia |
Outcome Measure |
Uric acid T-cell surface antigen CD4 T-Cell differentiation antigen CD8 Hematopoietic progenitor cell antigen CD34 Fc fragment of IgG receptor Ib |
|
|
eosinophilia |
Brief Title |
Interleukin-5 (IL-5) |
|
|
eosinophilia |
Detailed Description |
T-cell surface antigen CD4 T-Cell differentiation antigen CD8 Hematopoietic progenitor cell antigen CD34 Fc fragment of IgG receptor Ib |
|
|
eosinophilia |
Eligibility Criteria |
filamin C, gamma COPD |
|
|
eosinophilia |
Official Title |
Interleukin-5 (IL-5) |
|
|
eosinophilia |
Brief Summary |
T-cell surface antigen CD4 T-Cell differentiation antigen CD8 Hematopoietic progenitor cell antigen CD34 Fc fragment of IgG receptor Ib |
|
|
eosinophilic oesophagitis |
Brief Title |
Interleukin-5 (IL-5) |
|
|
eosinophilic oesophagitis |
Official Title |
Interleukin-5 (IL-5) |
|
|
eosinophilic oesophagitis |
Outcome Measure |
D-Urobilinogen Bilirubin |
|
|
hypereosinophilic syndrome |
Brief Title |
Interleukin-5 (IL-5) |
|
|
hypereosinophilic syndrome |
Official Title |
Interleukin-5 (IL-5) |
|
|
nasal polyps |
Brief Title |
Interleukin-5 (IL-5) |
|
|
nasal polyps |
Official Title |
Interleukin-5 (IL-5) |
|
|
sinusitis |
Brief Title |
Interleukin-5 (IL-5) |
|
|
sinusitis |
Official Title |
Interleukin-5 (IL-5) |
Biomarker
| Drug Name | Biomarker Name | Biomarker Function |
|---|---|---|
| Reslizumab - Teva Pharmaceuticals | ALT | Outcome Measure |
| Bilirubin | Outcome Measure | |
| COPD | Eligibility Criteria | |
| D-Urobilinogen | Outcome Measure | |
| Fc fragment of IgG receptor Ib | Brief Summary, Detailed Description, Outcome Measure | |
| filamin C, gamma | Eligibility Criteria | |
| gamma-glutamyltransferase 2 | Outcome Measure | |
| gamma-glutamyltransferase light chain 1 | Outcome Measure | |
| gamma-glutamyltransferase light chain 3 | Outcome Measure | |
| GGT | Outcome Measure | |
| GGTLC4P | Outcome Measure | |
| GGTLC5P | Outcome Measure | |
| Hematopoietic progenitor cell antigen CD34 | Brief Summary, Detailed Description, Outcome Measure | |
| interleukin 5 receptor subunit alpha | Arm Group Description, Arm Group Label | |
| Interleukin-5 (IL-5) | Brief Title, Official Title | |
| L-Aspartic acid | Outcome Measure | |
| LOC102724197 | Outcome Measure | |
| T-Cell differentiation antigen CD8 | Brief Summary, Detailed Description, Outcome Measure | |
| T-cell surface antigen CD4 | Brief Summary, Detailed Description, Outcome Measure | |
| Uric acid | Outcome Measure |
Development Status
Summary Table
| Indication | Qualifier | Patient Segment | Phase | Countries | Route / Formulation | Developers | Event Date |
|---|---|---|---|---|---|---|---|
| Asthma | - | - | Marketed | Austria, Belgium, Canada, Czech Republic, Denmark, Finland, Greece, Hungary, Israel, Netherlands, Norway, Poland, Portugal, Russia, Spain, Sweden, USA, United Kingdom | IV / Infusion | Teva Pharmaceutical Industries | 06 Feb 2023 |
| Asthma | - | - | Registered | Australia, European Union, Iceland, Liechtenstein | IV / Infusion | Teva Pharmaceutical Industries | 25 Jul 2017 |
| Asthma | - | - | Phase III | Argentina, Brazil, Chile, Colombia, India, Malaysia, Mexico, New Zealand, Peru, Philippines, South Africa, South Korea, Taiwan, Thailand, Ukraine | IV / Infusion | Teva Pharmaceutical Industries | 01 Apr 2011 |
| Asthma | - | In adolescents, In adults, In the elderly, Treatment-experienced | Discontinued (III) | Argentina, Australia, Belgium, Canada, Czech Republic, France, Germany, Hungary, Israel, Italy, Japan, Mexico, Netherlands, New Zealand, Poland, Romania, Russia, South Africa, South Korea, Spain, Turkey, USA, Ukraine | SC / Injection | Teva Pharmaceutical Industries | 19 Feb 2021 |
| Asthma | - | - | Discontinued (Preclinical) | USA | Intranasal / unspecified | Celltech R&D | 20 Mar 2003 |
| Churg-Strauss syndrome | - | - | Phase II | USA | IV / unspecified | Teva Pharmaceutical Industries | 12 Sep 2017 |
| Oesophagitis | Eosinophilic oesophagitis | In adolescents, In children | No development reported (III) | Canada, USA | IV / Infusion | Teva Pharmaceutical Industries | 18 May 2015 |
| Sinusitis | - | - | Phase III | USA | IV / unspecified | Allergy and Asthma Clinical Research | 01 Jun 2016 |
Orphan Status
| Indication | Patient Segment | Country | Organisation | Event Date |
|---|---|---|---|---|
| Oesophagitis | In adolescents, In children | USA | Ception Therapeutics | 05 Mar 2008 |
Commercial Information
Involved Organisations
| Organisation | Involvement | Countries |
|---|---|---|
| Schering-Plough | Originator | USA |
| Celltech R&D | Originator | United-Kingdom |
| Schering-Plough | Owner | USA |
| Celltech R&D | Owner | United-Kingdom |
| Teva Pharmaceutical Industries | Licensee | Israel |
| Allergy and Asthma Clinical Research | Collaborator | USA |
| National Jewish Health | Collaborator | USA |
| McMaster University | Collaborator | Canada |
Brand Names
| Brand Name | Organisations | Indications | Countries |
|---|---|---|---|
| CINQAERO | Teva Pharmaceutical Industries | Asthma | European Union, Russia |
| CINQAIR | Teva Pharmaceutical Industries | Asthma | Australia, Canada, Israel, USA |
| Cinquil | Teva Pharmaceutical Industries | Asthma, Oesophagitis | - |
Scientific Summary
Pharmacokinetics
Preclinical studies
ovalbumin-sensitized mice were treated with TRFK-5 100µg delivered either by the intranasal or intraperitoneal routes prior to ovalbumin airway challenge. The intraperitoneal formulation produced TRFK-5 serum concentrations > 40 µg·ml−1. The intranasal formulation produced a serum concentration of 1226 ng·ml−1 [41] .
Clinical studies
the plasma half-life of reslizumab was approximately 25 days in patients with asthma. The drug was still detectable in blood 3 months after administration [47] .
Adverse Events
According to post-hoc analysis of two pivotal phase III trials, asthma, nasopharyngitis, upper respiratory infections, sinusitis, influenza and headache were the common adverse events (> 5% of patients) occurring in the reslizumab treatment arm when compared with placebo (NCT01287039; NCT01285323). Two patients in the reslizumab arm, experienced anaphylactic reactions, eventually these patients withdrew from the study. Both the patients responded to standard treatment administered at the study centre. In two phase III trials, adverse events (AEs) observed in reslizumab treated group were comparable with the placebo group. The most common AEs were observed in >5% patients, the most frequent being asthma, headache and upper respiratory tract infections. The randomised, double-blind trials enrolled a total of 953 patients aged 12-75 years [25] [24] . In another phase III trial, the most common AEs were asthma, headache, nasopharyngitis and upper respiratory tract infections. The majority of AEs were comparable across treatment groups and were considered mild to moderate. The trial evaluated reslizumab 3 mg/kg and 0.3 mg/kg intravenous injection every 4 weeks in patients with uncontrolled moderate to severe asthma with elevated eosinophils, treated with standard of care therapies [29] .
Reslizumab was well tolerated, with an adverse event profile comparable to placebo, according to interim results of a 4-month phase IIb/III trial (Res-05-0002) in 226 children and adolescents with eosinophilic oesophagitis. Reslizumab was dosed once-monthly at 1, 2 and 3 mg/kg [4] .
Pharmacodynamics
Summary
Preclinical studies
TRFK-5 inhibited the ovalbumin-induced accumulation of eosinophils and total cells in the bronchoalveolar lavage fluid of guinea-pigs. Pretreatment also inhibited eosinophil accumulation in the bronchi and bronchioles, and almost completely protected against substance P-induced airway hyperreactivity [48] .
Ovalbumin-sensitised mice were treated with TRFK-5 100µg delivered either by the intranasal or intraperitoneal routes prior to ovalbumin airway challenge. TRFK-5 delivered via either route significantly decreased the number of eosinophils and significantly increased the number of macrophages in bronchoalveolar lavage fluid, relative to mice receiving no antibody treatment or mice receiving an isotype-matched control antibody. Lung histopathology analysis showed that intranasally administered TRFK-5 significantly reduced the degree of lung tissue inflammatory cell changes induced by ovalbumin challenge. The effect of intraperitoneally delivered TRFK-5 was similar, but the intranasal formulation was significantly more effective at reducing lung tissue eosinophil numbers. TRFK-5 delivered either intranasally or intraperitoneally before ovalbumin challenge significantly reduced the average response to methacholine of ovalbumin-sensitised mice [41] .
Ovalbumin-sensitised mice received either intranasally delivered TRFK-5 (50µg) or intraperitoneally delivered anti-IgE antibody 1-5 (200µg; a nonanaphylactogenic rat anti-mouse antibody) before ovalbumin airway challenge. Anti-IgE antibody treatment significantly reduced serum anti-ovalbumin IgE levels and prevented anaphylaxis development but did not affect T cell function, eosinophil airway infiltration or airway hyperresponsiveness. TRFK-5 treatment did not affect the function of B cells, T cells or mast cells, but completely suppressed eosinophilic lung inflammation and airway hyperresponsiveness [42] .
Clinical studies
in a multicentre, randomised, parallel-group study, 32 patients with severe persistent asthma received a single dose of intravenous reslizumab at dosages of 0.03, 0.1, 0.3 or 1.0 mg/kg/dose. The highest dose (1.0 mg/kg/dose) of reslizumab significantly reduced blood eosinophil counts [51] .
Therapeutic Trials
In a 4-month phase IIb/III trial (Res-05-0002) in 226 children and adolescents with eosinophilic oesophagitis, those randomised to reslizumab had a significant reduction in peak oesophageal eosinophil levels (p<0.0001 vs placebo for all dose levels). In the second co-primary endpoint, patients treated with reslizumab showed an improvement in their clinical symptoms, but this improvement was not significantly different to that of the placebo group. Reslizumab was dosed once-monthly at 1, 2 and 3 mg/kg [4] .
Pooled analysis results
Pooled results from two duplicate 52-weeks, placebo-controlled phase III trials of 3 mg/kg reslizumab administered intravenously every four weeks demonstrated FEV1 (forced expiratory volume change in one second) of ≥430mL (highest quartile) to ≤-100mL (lowest quartile); ACQ-6 (Asthma Control Questionnaire) changes of ≥-2.00 to ≤-0.67 and AQLQ (Asthma Quality of Life Questionnaire) changes of ≥2.00 to ≤0.44. For FEV1 (highest vs lowest quartile), baseline characteristics that differed significantly were: proportion using OCS (22% vs 11%, p = 0.0356), mean ACQ-6 (2.71 vs 2.39, p = 0.0137), and mean blood EOS (858 vs 514 cells/μL, p = 0.0008). For ACQ-6: baseline mean blood EOS (824 vs 551, p = 0.0094) and mean age of asthma onset (30 vs 23 years, p = 0.0044). For AQLQ: baseline mean ACQ-6 (3.08 vs 2.20, p < 0.0001), mean blood EOS (829 vs 577, p = 0.0183), and mean asthma age of onset (29 vs 23, p = 0.0383). Earlier reported data showed reduced frequency of asthma exacerbations and improved asthma control, lung function and quality of life in patients. In the overall patient population (n = 953), reductions in clinical asthma exacerbations (CAE) was 67% (95% CI:29%, 85%) in patients ≥65 years (n = 77), while that in patients of age 18-64 years old (n = 851) was 53% (95% CI:40%, 64%). The mean change in FEV1 was 150mL (95% CI:17, 283) and 126mL (95% CI:67, 184), in ACQ-7 was -0.997 (95% CI:-1.447, -0.547) and -0.305 (95% CI:-0.438, -0.173); and was 0.876 (95% CI:0.417, 1.336) and 0.316 (95% CI:0.169, 0.462) in AQLQ as compared to placebo at 52 weeks in patients ≥65 and in younger adults (18-64 years), repectively.The observed improvements in patients ≥65 years, were numerically larger than for younger adults, indicating changes in ACQ-7 and AQLQ both exceeding the minimally important difference for the measure [26] . Additional data from 953 randomised patients amongst which 150 (16%) had chronic sinusitis with nasal polyps (CSwNP) and 252 (26%) patients with chronic sinusitis alone (CS) suggested that the patients received significant therapeutic benefit with reslizumab. As compared with placebo, 83% and 70% reduction in annual rate of CAE was observed in patients with CSwNP (RR 0.17 [95% CI: 0.10, 0.32]; p=0.0002) and CS alone (RR 0.30 [95% CI: 0.20, 0.44]; p=0.0103), respectively [49] . Clinically significant results from the trials investigating AQLQ, as defined by (activity limitations [AL], symptoms [S], emotional function [EF] and environmental stimuli [ES]) indicated significant differences (≥ 0.5) from the baseline at week 52. The differences between study 1 and study 2 for AL was 0.335(study1) and 0.219(study2), p ≤ 0.05(both studies), for S was defined as 0.393(study1) and 0.383(study2), p≤0.05(both studies), for EF was defined as 0.411(study1) and 0.375(study2), p≤0.05(both studies), and for ES was defined as 0.419(study1) and 0.013(study2), p≤0.05(study1)/NSD(study2). Minimally important difference from baseline for AL, S, EF and ES was 67%, 79% and 77%, 72% and 76% and 60% for the reslizumab groups while it was 59% and 61%, 68%, 61% and 60% and 67% and 63% for the placebo groups, respectively [50] . Updated results demonstrated that 11% patients had ASA sensitivity and 6% (n = 56) patients had CRSwNP. Forty-eight patients with ASA sensitivity and treated with reslizumab had a reduction of 62% in the annual rate of CAE (RR 0.38 [95% CI 0.21, 0.70]). Furthermore, 79% reduction in the annual rate of CAE was observed in patients with ASA sensitivity and known CRSwNP (RR 0.21 [95% CI 0.08, 0.58]). Both the groups achieved clinically meaningful improvements in FEV in 1 second [27] [28] [21] [22] .
According to a post-hoc analysis of two pivotal phase III trials, in the subgroup of patients with late onset asthma, reslizumab showed a 75% reduction in asthma exacerbation and improvement in lung function as measured by forced expiratory volume in one second. In the overall pooled patient population, treatment with reslizumab reduced asthma exacerbations by 54%, while in the subgroup of patients diagnosed with asthma at <40 years of age, exacerbations were reduced by 42%. Treatment with reslizumab, in two phase III trials, showed significant reductions in the frequency of clinical asthma exacerbation in patients with inadequately controlled moderate to severe asthma with elevated levels of blood eosinophil. The reductions were 50% and 60% in both trials respectively, compared with placebo (p < 0.0001). Reslizumab also showed positive effect on lung function (as measured by overall change in forced expiratory volume in 1 second; FEV1) and asthma control (using the Asthma Control Questionnaire [ACQ]). The randomised, double-blind trials enrolled a total of 953 patients aged 12-75 years [25] [24] . In another phase III trial, significant improvements in lung function versus placebo and in patient reported asthma control were also noted. Improvements were observed 4 weeks after initial dose administration and were sustained until the end of the 16-week treatment period. The trial evaluated reslizumab 3.0 mg/kg and 0.3 mg/kg intravenous injection every 4 weeks in patients with uncontrolled moderate to severe asthma with elevated eosinophils, treated with standard of care therapies. FEV1 and ACQ improvements for the 0.3 mg/kg dose were numerically less than those for the 3 mg/kg dose [29] .
Development History
| Event Date | Update Type | Comment |
|---|---|---|
| 06 Feb 2023 | Phase Change - Marketed | Launched for Asthma in Austria, Greece, Belgium, Finland, Spain, Denmark, Sweden, Portugal, Czech Republic, Netherlands, Poland, Hungary, United Kingdom, Russia, Norway (IV) prior to February 2023 [6] Updated 06 Jun 2023 |
| 05 Oct 2022 | Phase Change - Marketed | Launched for Asthma in Canada (IV) as of October 2022 Updated 06 Jun 2023 |
| 19 Jan 2022 | Phase Change - Marketed | Launched for Asthma in Israel (IV) as of January 2022 Updated 06 Jun 2023 |
| 23 Aug 2021 | Biomarker Update | Biomarkers information updated Updated 24 Oct 2021 |
| 19 Feb 2021 | Phase Change - Discontinued(III) | Discontinued - Phase-III for Asthma (In adolescents, In the elderly, Treatment-experienced, In adults) in New Zealand, Poland, Belgium, Russia, Australia, Hungary, South Africa, Spain, Ukraine, Argentina, France, Germany, Czech Republic, Israel, Italy, Mexico, South Korea, Canada, Netherlands, Japan, Turkey, Romania, USA (SC) (Teva Pharmaceuticals pipeline, February 2021) Updated 19 Feb 2021 |
| 10 Feb 2021 | Trial Update | National Jewish Health completes a phase II trial in Churg-Strauss syndrome in USA (IV) (NCT02947945) Updated 19 Feb 2021 |
| 02 Mar 2018 | Scientific Update | Pooled efficacy data from two phase III trials in Asthma presented at the 2018 Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAI-2018) [27] Updated 23 Mar 2018 |
| 22 Feb 2018 | Trial Update | Teva terminates a phase III open-label extension trial as the parent studies didn't meet their primary endpoint in Asthma (In adolescents, In adults, In the elderly) in USA, Belgium, Czech Republic, Hungary, Germany, France, Spain, Poland, Canada, Israel, Romania, Russia and Ukraine (SC) (NCT03052725) Updated 23 May 2018 |
| 31 Jan 2018 | Trial Update | Teva completes a phase III trial in Asthma (In adolescents, In the elderly, Treatment-experienced, In adults) in USA, Australia, Argentina, Belgium, Canada, Japan, Turkey, Romania, New Zealand, Poland, Russia, South Africa, Ukraine, Czech Republic, Hungary, Spain, France, Germany, Israel, Italy, South Korea, Mexico and Netherlands (SC) (NCT02452190) Updated 03 Apr 2018 |
| 04 Dec 2017 | Trial Update | Teva completes a phase III study in Asthma (In adolescents, In adults, In the elderly, Treatment-experienced) in USA, Australia, Czech Republic, Poland, Argentina, Belgium, France, Germany, Hugery, Israel, Italy, Mexico, South Korea, the Netherlands, Russia, Spain, Ukrain (NCT02501629) Updated 28 Dec 2017 |
| 13 Nov 2017 | Regulatory Status | The Scottish Medicines Consortium rejects reslizumab for routine use by NHS Scotland for the treatment of Eosinophilic asthma [7] Updated 17 Nov 2017 |
| 12 Sep 2017 | Phase Change - II | Phase-II clinical trials in Churg-Strauss syndrome in USA (IV) (NCT02947945) Updated 28 Sep 2017 |
| 25 Jul 2017 | Phase Change - Registered | Registered for Asthma in Australia (IV) [18] Updated 26 Sep 2017 |
| 20 Jul 2017 | Regulatory Status | The National Institute for Health and Care Excellence recommends reslizumab for Eosinophilic Asthma [8] Updated 25 Jul 2017 |
| 07 Jul 2017 | Regulatory Status | The German Federal Joint Committee issues added benefit opinion for reslizumab for Asthma [19] Updated 10 Jul 2017 |
| 13 Mar 2017 | Trial Update | Teva initiates a phase III open-label extension trial in Asthma (In adolescents, In adults, In the elderly) in USA, Belgium, Czech Republic, Hungary (NCT03052725; EudraCT2016-004661-23) Updated 24 Apr 2017 |
| 10 Mar 2017 | Trial Update | Teva initiates a phase III open-label extension trial in Asthma (In adolescents, In adults, In the elderly) in Germany, France, Spain, Poland, Canada, Israel, Romania, Russia and Ukraine (SC) (NCT03052725) (EudraCT2016-004661-23) after March 2017 Updated 23 May 2018 |
| 06 Mar 2017 | Trial Update | Teva completes a phase III trial in Asthma in France (IV) (EudraCT2014-002659-25) Updated 20 Mar 2019 |
| 03 Mar 2017 | Scientific Update | Updated pooled efficacy data from two phase III trials in Asthma presented at the 2017 Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI-2017) [28] Updated 22 Mar 2017 |
| 16 Feb 2017 | Trial Update | Teva Pharmaceutical plans a phase III trial for Asthma (NCT03052725) Updated 16 Feb 2017 |
| 18 Aug 2016 | Phase Change - Registered | Registered for Asthma in Liechtenstein, Iceland, Norway, European Union (IV) [14] Updated 22 Aug 2016 |
| 25 Jul 2016 | Phase Change - Registered | Registered for Asthma in Canada (IV) [13] Updated 29 Jul 2016 |
| 04 Jul 2016 | Trial Update | Teva initiates a phase III trial in Asthma in France(IV) (EudraCT2014-002659-25) Updated 20 Mar 2019 |
| 24 Jun 2016 | Regulatory Status | The Committee for Medicinal Products for Human Use (CHMP) recommends approval of reslizumab for Asthma in European Union [15] Updated 27 Jun 2016 |
| 07 Jun 2016 | Phase Change - Marketed | Launched for Asthma in USA before June 2016 (IV) Updated 28 Oct 2016 |
| 01 Jun 2016 | Phase Change - III | Phase-III clinical trials in Sinusitis in USA (IV) (NCT02799446) Updated 17 Jun 2016 |
| 23 Mar 2016 | Phase Change - Registered | Registered for Asthma in USA (IV) - First global approval [9] Updated 28 Mar 2016 |
| 04 Mar 2016 | Scientific Update | Pooled efficacy data from two phase III trials in Asthma presented at the 2016 Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI-2016) [26] Updated 17 Mar 2016 |
| 10 Dec 2015 | Phase Change - Preregistration | Preregistration for Asthma in Canada (IV) [11] Updated 12 Dec 2015 |
| 10 Dec 2015 | Regulatory Status | The Pulmonary-Allergy Drugs Advisory Committee recommends approval of reslizumab for Asthma in USA [11] Updated 12 Dec 2015 |
| 01 Oct 2015 | Trial Update | McMaster University and Teva Pharmaceuticals initiate a phase II/III trial for Asthma in Canada (IV) (NCT02559791) Updated 24 Feb 2016 |
| 01 Oct 2015 | Phase Change - III | Phase-III clinical trials in Asthma (In adolescents, In the elderly, In adults, Treatment-experienced) in Hungary (SC) Updated 27 Oct 2015 |
| 01 Oct 2015 | Phase Change - III | Phase-III clinical trials in Asthma (In adolescents, Treatment-experienced, In adults, In the elderly) in Spain and Czech Republic (SC) Updated 16 Oct 2015 |
| 27 Sep 2015 | Scientific Update | Efficacy and adverse events data from two phase III trials in Asthma presented at 25th Annual Congress of the European Respiratory Society (ERS-2015) [25] Updated 20 Oct 2015 |
| 22 Sep 2015 | Phase Change - III | Phase-III clinical trials in Asthma (In adolescents, In the elderly, Treatment-experienced, In adults) in Romania, Turkey, Japan, Canada (SC) (NCT02452190) Updated 03 Apr 2018 |
| 22 Sep 2015 | Phase Change - III | Phase-III clinical trials in Asthma (In adolescents, In the elderly, Treatment-experienced, In adults) in Netherlands, South Korea, Mexico, Italy, Israel, Germany, France, Argentina (SC) (NCT02501629) Updated 28 Dec 2017 |
| 22 Sep 2015 | Trial Update | Teva initiates a phase III study in Asthma (In adolescents, In adults, In the elderly, Treatment-experienced) in Belgium, Hugery, Russia, Spain, Ukrain (NCT02501629) Updated 28 Dec 2017 |
| 01 Sep 2015 | Phase Change - III | Phase-III clinical trials in Asthma (In adolescents, In the elderly, Treatment-experienced, In adults) in Ukraine, South Africa, Russia, Poland, New Zealand, Belgium, Australia (SC) after September 2015 (NCT02452190) Updated 28 Mar 2016 |
| 01 Sep 2015 | Trial Update | Teva initiates a phase III study in Asthma (In adolescents, In adults, In the elderly, Treatment-experienced) in Australia, Czech Republic and Poland (SC) after September 2015 (NCT02501629) Updated 28 Mar 2016 |
| 01 Sep 2015 | Trial Update | Teva initiates a phase III study in Asthma (In adolescents, In adults, In the elderly, Treatment-experienced) in USA (SC) (NCT02501629) Updated 19 Nov 2015 |
| 01 Sep 2015 | Phase Change - III | Phase-III clinical trials in Asthma (In adults, In adolescents, Treatment-experienced, In the elderly) in USA (SC) (NCT02452190) Updated 01 Oct 2015 |
| 28 Jul 2015 | Phase Change - Preregistration | Preregistration for Asthma in European Union (IV) Updated 30 Jul 2015 |
| 20 Jul 2015 | Trial Update | Teva plans a phase III trial for Asthma in USA (NCT02501629) Updated 20 Jul 2015 |
| 15 Jun 2015 | Phase Change - Preregistration | Preregistration for Asthma in USA (IV) Updated 17 Jun 2015 |
| 29 May 2015 | Trial Update | Teva plans a phase III trial for Asthma (In adolescents, In adults) in USA (NCT02452190) Updated 29 May 2015 |
| 18 May 2015 | Active Status Review | Reslizumab is still in phase-III development for Asthma in Canada Updated 10 Sep 2015 |
| 18 May 2015 | Phase Change - No development reported(III) | No development reported - Phase-III for Oesophagitis (In adolescents, In children) in USA, Canada (IV) Updated 18 May 2015 |
| 13 Feb 2015 | Trial Update | Teva terminates enrolment in a phase III extension trial for Asthma in USA, Argentina, Australia, Belgium, Brazil, Canada, Columbia, Czech Republic, Denmark, France, Germany, Greece, Hungary, Israel, South Korea, Malaysia, Mexico, Netherlands, New Zealand, Peru, Philippines, Poland, Romania, Russia, Slovakia, South Africa, Sweden, Taiwan, Thailand and Ukraine (NCT01290887) Updated 26 Feb 2015 |
| 11 Feb 2015 | Patent Information | Teva has patent protection for reslizumab in USA and European Union (Teva 20-F, February 2015) Updated 05 Nov 2015 |
| 08 Sep 2014 | Scientific Update | Efficacy and adverse events data from a phase III trial in Asthma released by Teva [29] Updated 11 Sep 2014 |
| 02 Sep 2014 | Scientific Update | Efficacy and adverse events data from two phase III trials in Asthma released by Teva [24] Updated 06 Sep 2014 |
| 01 May 2014 | Trial Update | Teva completes a phase III trial in Asthma in USA, Canada, Argentina, Brazil, France, Germany, Greece, India, South Korea, Mexico, Peru, Romania, Russia, Slovakia, Taiwan and Ukraine (NCT01285323) Updated 22 Jul 2014 |
| 01 Apr 2014 | Trial Update | Cephalon completes a phase III trial in Asthma in Australia, Belgium, Chile, Colombia, Czech Republic, Denmark, Hungary, Israel, Malaysia, New Zealand, Philippines, Poland, Russia, South Africa, Sweden, Thailand and USA (NCT01287039) Updated 01 Jul 2014 |
| 01 Mar 2014 | Trial Update | Cephalon completes a phase I bioavailability trial in Healthy volunteers in USA (NCT01990443) Updated 09 Jun 2014 |
| 22 Jan 2014 | Trial Update | Cephalon completes enrolment in its phase I bioavailability trial in Healthy volunteers in USA (NCT01990443) Updated 11 Mar 2014 |
| 11 Jan 2014 | Trial Update | Cephalon completes a phase III trial in Asthma in Argentina, Belgium, Brazil, Canada, Colombia, France, Hungary, Israel, Mexico, Netherlands, Poland, Romania, Sweden and USA (NCT01270464) Updated 03 Feb 2014 |
| 01 Oct 2013 | Trial Update | Cephalon completes a phase III in Asthma in USA (NCT01508936) Updated 21 Nov 2013 |
| 30 Jun 2013 | Phase Change - I | Phase-I clinical trials in Asthma in USA (SC) Updated 27 Nov 2013 |
| 26 Feb 2013 | Trial Update | Cephalon completes enrolment in its phase III trial for Asthma in USA, Argentina, Belgium, Canada, Colombia, Hungary, Israel, Mexico, Netherlands, Poland and Sweden (NCT01270464) Updated 11 Mar 2013 |
| 07 Feb 2013 | Trial Update | Cephalon completes enrolment in its phase III trial for Asthma in USA (NCT01508936) Updated 15 Mar 2013 |
| 06 Feb 2013 | Trial Update | Cephalon completes enrolment in its phase III trial for Asthma in USA, Canada, Argentina, Brazil, France, Germany, Greece India, South Korea, Mexico, Peru, Romania, Russia, Slovakia, Taiwan and Ukraine (NCT01285323) Updated 11 Mar 2013 |
| 06 Feb 2013 | Trial Update | Cephalon completes enrolment in its phase III trial for Asthma in Australia, Belgium, Chile, Colombia, Czech Republic, Denmark, Hungary, Israel, Malaysia, New Zealand, Philippines, Poland, Russia, South Africa, Sweden, Thailand and USA (NCT01287039) Updated 11 Mar 2013 |
| 31 Jan 2012 | Trial Update | Ception Therapeutics completes a phase III trial in eosinophilic Oesophagitis (in paediatric and adolescent patients) in USA and Canada (NCT00635089) Updated 11 Mar 2013 |
| 01 Jan 2012 | Trial Update | Cephalon initiates a phase III trial in Asthma in USA (NCT01508936) Updated 15 Mar 2013 |
| 14 Oct 2011 | Company Involvement | Cephalon has been acquired by Teva Pharmaceutical Industries Updated 20 Feb 2015 |
| 01 Jun 2011 | Trial Update | Cephalon initiates enrolment in a phase III extension trial for Asthma in Argentina, Australia, Belgium, Brazil, Canada, Columbia, Czech Republic, Denmark, France, Germany, Greece, Hungary, Israel, South Korea, Malaysia, Mexico, Netherlands, New Zealand, Peru, Philippines, Poland, Romania, Russia, Slovakia, South Africa, Sweden, Taiwan, Thailand and Ukraine (NCT01290887) after June 2011 Updated 26 Feb 2015 |
| 01 Jun 2011 | Trial Update | Cephalon initiates enrolment in a phase III extension trial for Asthma in USA (NCT01290887) Updated 03 Jun 2011 |
| 17 May 2011 | Phase Change - III | Phase-III clinical trials in Asthma in Canada (IV) Updated 22 Jun 2011 |
| 01 Apr 2011 | Phase Change - III | Phase-III clinical trials in Asthma in Australia (IV) Updated 11 Mar 2013 |
| 01 Apr 2011 | Phase Change - III | Phase-III clinical trials in Asthma in Chile (IV) Updated 11 Mar 2013 |
| 01 Apr 2011 | Phase Change - III | Phase-III clinical trials in Asthma in Czech Republic (IV) Updated 11 Mar 2013 |
| 01 Apr 2011 | Phase Change - III | Phase-III clinical trials in Asthma in Denmark (IV) Updated 11 Mar 2013 |
| 01 Apr 2011 | Phase Change - III | Phase-III clinical trials in Asthma in Malaysia (IV) Updated 11 Mar 2013 |
| 01 Apr 2011 | Phase Change - III | Phase-III clinical trials in Asthma in New Zealand (IV) Updated 11 Mar 2013 |
| 01 Apr 2011 | Phase Change - III | Phase-III clinical trials in Asthma in Philippines (IV) Updated 11 Mar 2013 |
| 01 Apr 2011 | Phase Change - III | Phase-III clinical trials in Asthma in South Africa (IV) Updated 11 Mar 2013 |
| 01 Apr 2011 | Phase Change - III | Phase-III clinical trials in Asthma in Thailand (IV) Updated 11 Mar 2013 |
| 14 Mar 2011 | Phase Change - III | Phase-III clinical trials in Asthma in Brazil (IV) Updated 11 Mar 2013 |
| 14 Mar 2011 | Phase Change - III | Phase-III clinical trials in Asthma in France (IV) Updated 11 Mar 2013 |
| 14 Mar 2011 | Phase Change - III | Phase-III clinical trials in Asthma in Germany (IV) Updated 11 Mar 2013 |
| 14 Mar 2011 | Phase Change - III | Phase-III clinical trials in Asthma in Greece (IV) Updated 11 Mar 2013 |
| 14 Mar 2011 | Phase Change - III | Phase-III clinical trials in Asthma in India (IV) Updated 11 Mar 2013 |
| 14 Mar 2011 | Phase Change - III | Phase-III clinical trials in Asthma in Peru (IV) Updated 11 Mar 2013 |
| 14 Mar 2011 | Phase Change - III | Phase-III clinical trials in Asthma in Romania (IV) Updated 11 Mar 2013 |
| 14 Mar 2011 | Phase Change - III | Phase-III clinical trials in Asthma in Russia (IV) Updated 11 Mar 2013 |
| 14 Mar 2011 | Phase Change - III | Phase-III clinical trials in Asthma in Slovakia (IV) Updated 11 Mar 2013 |
| 14 Mar 2011 | Phase Change - III | Phase-III clinical trials in Asthma in South Korea (IV) Updated 11 Mar 2013 |
| 14 Mar 2011 | Phase Change - III | Phase-III clinical trials in Asthma in Taiwan (IV) Updated 11 Mar 2013 |
| 14 Mar 2011 | Phase Change - III | Phase-III clinical trials in Asthma in Ukraine (IV) Updated 11 Mar 2013 |
| 14 Mar 2011 | Trial Update | Cephalon initiates enrolment in two phase III trials for Asthma in USA (NCT01287039 & NCT01285323) Updated 24 Mar 2011 |
| 25 Jan 2011 | Phase Change - III | Phase-III clinical trials in Asthma in Argentina (IV) Updated 11 Mar 2013 |
| 25 Jan 2011 | Phase Change - III | Phase-III clinical trials in Asthma in Belgium (IV) Updated 11 Mar 2013 |
| 25 Jan 2011 | Phase Change - III | Phase-III clinical trials in Asthma in Colombia (IV) Updated 11 Mar 2013 |
| 25 Jan 2011 | Phase Change - III | Phase-III clinical trials in Asthma in Hungary (IV) Updated 11 Mar 2013 |
| 25 Jan 2011 | Phase Change - III | Phase-III clinical trials in Asthma in Israel (IV) Updated 11 Mar 2013 |
| 25 Jan 2011 | Phase Change - III | Phase-III clinical trials in Asthma in Mexico (IV) Updated 11 Mar 2013 |
| 25 Jan 2011 | Phase Change - III | Phase-III clinical trials in Asthma in Netherlands (IV) Updated 11 Mar 2013 |
| 25 Jan 2011 | Phase Change - III | Phase-III clinical trials in Asthma in Poland (IV) Updated 11 Mar 2013 |
| 25 Jan 2011 | Phase Change - III | Phase-III clinical trials in Asthma in Sweden (IV) Updated 11 Mar 2013 |
| 25 Jan 2011 | Phase Change - III | Phase-III clinical trials in Asthma in USA (IV) Updated 25 Feb 2011 |
| 01 Dec 2010 | Trial Update | Teva initiates enrolment in a phase III trial for Asthma in Canada, Argentina, Brazil, France, Colombia, Mexico, Poland, Israel, Belgium, Hungary, Netherlands and Sweden (NCT01270464) Updated 28 Mar 2016 |
| 06 Aug 2010 | Trial Update | Cephalon completes a phase II trial in Asthma in USA & Canada (NCT00587288) Updated 25 Mar 2011 |
| 02 May 2010 | Trial Update | Ception Therapeutics completes enrolment in its phase-III trial [NCT00635089] for eosinophilic oesophagitis in adolescents and children in the USA and Canada Updated 10 Aug 2010 |
| 05 Apr 2010 | Company Involvement | Ception Therapeutics has been acquired by Cephalon Updated 07 Apr 2010 |
| 24 Nov 2009 | Scientific Update | Interim efficacy & adverse events data from the phase IIb/III Res-05-0002 trial in Eosinophilic oesophagitis released by Ception [4] Updated 25 Nov 2009 |
| 31 May 2008 | Phase Change - III | Phase-III clinical trials in Eosinophilic oesophagitis in Canada (IV) Updated 10 Feb 2009 |
| 31 May 2008 | Phase Change - III | Phase-III clinical trials in Eosinophilic oesophagitis in USA (IV) Updated 10 Feb 2009 |
| 10 Mar 2008 | Phase Change - II/III | Phase-II/III clinical trials in Eosinophilic oesophagitis in Canada (IV) Updated 10 Feb 2009 |
| 10 Mar 2008 | Phase Change - II/III | Phase-II/III clinical trials in Eosinophilic oesophagitis in USA (IV) Updated 10 Mar 2008 |
| 10 Mar 2008 | Regulatory Status | Reslizumab receives orphan drug status for paediatric eosinophilic oesophagitis in USA Updated 10 Mar 2008 |
| 20 Dec 2007 | Phase Change - Preclinical | Preclinical trials in Eosinophilic oesophagitis in USA (IV) Updated 23 Jan 2008 |
| 30 Nov 2007 | Phase Change - II | Phase-II clinical trials in Asthma in USA (IV) Updated 10 Feb 2009 |
| 30 Nov 2007 | Licensing Status | Reslizumab has been licensed to Ception Therapeutics Updated 23 Jan 2008 |
| 30 Nov 2007 | Phase Change - II | Phase-II clinical trials in Asthma in Canada (IV) Updated 23 Jan 2008 |
| 20 Mar 2003 | Phase Change - Discontinued(II) | Discontinued - Phase-II for Asthma in Belgium (Injection) Updated 20 Mar 2003 |
| 20 Mar 2003 | Phase Change - Discontinued(II) | Discontinued - Phase-II for Asthma in USA (Injection) Updated 20 Mar 2003 |
| 20 Mar 2003 | Phase Change - Discontinued(Preclinical) | Discontinued - Preclinical for Asthma in USA (Intranasal) Updated 20 Mar 2003 |
| 02 May 2001 | Company Involvement | Celltech Chiroscience Discovery is now called Celltech R&D Updated 02 May 2001 |
| 02 Feb 2000 | Company Involvement | Medeva has been merged into Celltech Chiroscience, which is now called Celltech Group Updated 02 Feb 2000 |
| 22 Oct 1999 | Company Involvement | Celltech has merged with Chiroscience to form Celltech Chiroscience Updated 22 Oct 1999 |
| 14 Oct 1999 | Scientific Update | A preclinical study of intranasal TRFK-5 has been added to the pharmacodynamics section [42] Updated 14 Oct 1999 |
| 07 Sep 1999 | Phase Change - Preclinical | Preclinical development for Asthma in USA (Intranasal) Updated 07 Sep 1999 |
| 07 Sep 1999 | Scientific Update | A preclinical study of intranasal TRFK-5 has been added to the pharmacodynamics section [41] Updated 07 Sep 1999 |
| 18 Jan 1999 | Scientific Update | Clinical data have been added to the pharmacokinetics section [47] Updated 18 Jan 1999 |
| 19 Jun 1998 | Phase Change - II | Phase-II clinical trials for Asthma in Belgium (Injection) Updated 19 Jun 1998 |
| 19 Jun 1998 | Phase Change - II | Phase-II clinical trials for Asthma in USA (Injection) Updated 19 Jun 1998 |
| 27 Nov 1997 | Phase Change - I | Phase-I clinical trials for Asthma in USA (Injection) Updated 27 Nov 1997 |
| 24 Oct 1997 | Phase Change - I | Phase-I clinical trials for Asthma in Belgium (Injection) Updated 24 Oct 1997 |
| 26 Apr 1995 | Phase Change - Preclinical | Preclinical development for Asthma in European Union (Unknown route) Updated 26 Apr 1995 |
| 26 Apr 1995 | Phase Change - Preclinical | Preclinical development for Asthma in USA (Unknown route) Updated 26 Apr 1995 |
References
-
Reslizumab BLA. Internet-Doc 2016;.
Available from: URL: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/Pulmonary-AllergyDrugsAdvisoryCommittee/UCM475759.pdf -
Teva Completes Acquisition of Cephalon.
Media Release -
Cephalon Signs Option Agreement to Acquire Ception Therapeutics.
Media Release -
Ception Therapeutics and Cephalon Provide Initial Results of a Phase IIb/III Study of CINQUIL in Pediatric Eosinophilic Esophagitis.
Media Release -
Cephalon Completes Acquisition of Ception Therapeutics.
Media Release -
REGENERON PHARMACEUTICALS - FORM 10K. Internet-Doc 2023;.
Available from: URL: https://www.sec.gov/ix?doc=/Archives/edgar/data/872589/000180422023000008/regn-20221231.htm -
SMC accepts three new medicines for use by NHSScotland.
Media Release -
NICE Recommends CINQAERO(Rm) (reslizumab) for the Treatment of Severe Eosinophilic Asthma.
Media Release -
Teva Announces FDA Approval of CINQAIR(R) (reslizumab) Injection.
Media Release -
FDA approves Cinqair to treat severe asthma.
Media Release -
FDA Advisory Committee Recommends Approval of Tevas Asthma Biologic Reslizumab.
Media Release -
Teva Announces FDA Acceptance of the Biologics License Application for Reslizumab.
Media Release -
Teva Canada Innovation Announces Approval of CINQAIR(TM) by Health Canada.
Media Release -
European Commission Grants Marketing Authorization for Tevas CINQAERO (reslizumab).
Media Release -
Teva Receives CHMP Positive Opinion for CINQAERO(R) (reslizumab).
Media Release -
Teva Announces European Medicines Agency (EMA) Confirms Successful Validation of Reslizumab Marketing Authorization Application.
Media Release -
Teva Announces European Medicines Agency (EMA) Confirms Successful Validation of Reslizumab Marketing Authorisation Application.
Media Release -
CINQAIR (reslizumab) approval by TGA, Australia. Internet-Doc 2017;.
Available from: URL: https://www.ebs.tga.gov.au/servlet/xmlmillr6?dbid=ebs/PublicHTML/pdfStore.nsf&docid=34EE29F58DCDC012CA258168004226E3&agid=(PrintDetailsPublic)&actionid=1 -
German Federal Joint Committee (G-BA) Confirms Evidence for Additional Benefit for CINQAERO(Rm) (reslizumab) in Severe Asthma Patients with an Elevated Eosinophil Count.
Media Release -
An Open-Label Safety Study of Patients with Severe Eosinophilic Asthma Who Were Previously Enrolled in the Reslizumab Open Label Extension Study C38072/3085
ctiprofile -
A 12-Month, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Reslizumab (3.0 mg/kg) in the Reduction of Clinical Asthma Exacerbations in Patients (12-75 Years of Age) With Eosinophilic Asthma
ctiprofile -
A 12-Month, Double-Blind, Placebo-Controlled, Parallel-Group Study to evaluate the Efficacy and Safety of Reslizumab (3.0 mg/kg) in the reduction of Clinical Asthma Exacerbations and Change in Lung Function in Patients (12-75 years of age) with Eosinophilic Asthma
ctiprofile -
The Lancet Respiratory Medicine and AAAAI Publish Positive Data from Phase III Trials of Tevas Reslizumab for the Treatment of Moderate to Severe Asthma in Patients with Elevated Blood Eosinophils.
Media Release -
Tevas Reslizumab Delivers Clinically and Statistically Significant Reduction in Asthma Exacerbations in Two Pivotal Phase III Studies.
Media Release -
Teva Presents New Reslizumab Data at European Respiratory Society (ERS) International Congress 2015.
Media Release -
Bernstein DI, Mansfield L, Zangrilli J, Garin M. Efficacy of Reslizumab in Older Patients (=65 years) with Asthma and Elevated Blood Eosinophils: Results from a Pooled Analysis of Two Phase 3, Placebo-Controlled Trials. AAAAI-2016 2016; abstr. 284.
Available from: URL: http://www.jacionline.org/ -
Chipps BE, McDonald M, Garin M. Baseline Characteristics Associated with Quartiles of Reslizumab Effect: Pooled Analysis Of Two Phase 3 Studies. AAAAI-WAO-2018 2018; abstr. 47.
Available from: URL: http://www.jacionline.org/article/S0091-6749(17)31949-8/fulltext -
Katial R, Hoyte F, Germinaro M, McDonald M. Efficacy of Reslizumab in Asthma Patients with Aspirin Sensitivity and Elevated Blood Eosinophils. AAAAI-2017 2017; abstr. 26.
Available from: URL: http://link.adisinsight.com/Ki4q2 -
Successful Completion of Phase III Program for Tevas Reslizumab Two More Phase Iii Studies Support the Benefits of Reslizumab Treatment in Asthma Patients with Eosinophilia.
Media Release -
A 16-Week, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Reslizumab (0.3 or 3.0 mg/kg) as Treatment for Patients (12-75 Years of Age) With Eosinophilic Asthma.
ctiprofile -
A 16-Week, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Reslizumab (3.0 mg/kg) Treatment in Patients With Moderate to Severe Asthma.
ctiprofile -
An Open-Label Extension Study to Evaluate the Long-Term Safety and Efficacy of Reslizumab (3.0 mg/kg) as Treatment for Patients With Eosinophilic Asthma Who Completed a Prior Teva-Sponsored Study in Eosinophilic Asthma
ctiprofile -
Route of Administration of Anti-IL5 Monoclonal Antibody in Prednisone-dependent Eosinophilic Asthma
ctiprofile -
An Efficacy and Safety Study of Reslizumab in the Treatment of Poorly Controlled Asthma in Subjects With Eosinophilic Airway Inflammation.
ctiprofile -
A Randomized, Open-Label, Parallel-Group, Single-Dose Study to Characterize the Absolute Bioavailability of Reslizumab (220 mg) Following Subcutaneous Administration to Healthy Subjects
ctiprofile -
Teva Announces Top-Line Results from Phase III Studies of Subcutaneously Administered Reslizumab in Patients with Severe Eosinophilic Asthma.
Media Release -
A 52-Week Double-Blind, Placebo-Controlled, Parallel-Group Efficacy and Safety Study of Reslizumab 110 mg Fixed, Subcutaneous Dosing in Patients With Uncontrolled Asthma and Elevated Blood Eosinophils
ctiprofile -
A Phase 3, 24-Week Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy and Safety Study of Reslizumab Subcutaneous Dosing (110 mg Every 4 Weeks) in Patients With Oral Corticosteroid Dependent Asthma and Elevated Blood Eosinophils
ctiprofile -
An Open-Label Extension Study of Reslizumab 110-mg Fixed, Subcutaneous Dosing in Patients 12 Years of Age and Older With Severe Eosinophilic Asthma
ctiprofile -
Efficacy of Reslizumab for the Treatment of Chronic Rhinosinusitis A Double Blind, Randomized, Placebo-controlled, Phase III Trial
ctiprofile -
Shardonofsky FR, Venzor III J, Barrios R, et al. Therapeutic efficacy of an anti-IL-5 monoclonal antibody delivered into the respiratory tract in a murine model of asthma. J-Allergy-Clin-Immunol 1999;.
PubMed | CrossRef Fulltext -
Hamelmann E, Cieslewicz G, Schwarze J, et al. Anti-interleukin 5 but not anti-IgE prevents airway inflammation and airway hyperresponsiveness. Am-J-Respir-Crit-Care-Med 1999;160934-941.
PubMed | CrossRef Fulltext -
Open-Label, to Evaluate the Efficacy and Safety of Reslizumab in the Treatment of Eosinophilic Granulomatosis With Polyangiitis (EGPA) Study: RITE Study
ctiprofile -
Ception Therapeutics Initiates Phase II/III Clinical Trial for Its Lead Product Reslizumab in Eosinophilic Esophagitis (EE) in Children.
Media Release -
An Efficacy and Safety Study of Reslizumab (CTx55700) in the Treatment of Eosinophilic Esophagitis in Subjects Aged 5 to 18 Years.
ctiprofile -
An Open-Label Safety and Efficacy Study of Reslizumab (CTx55700) for the Treatment of Pediatric Subjects With Eosinophilic Oesophagitis Who Completed Study Res-5-0002 [EXTENSION OF 700027517]
ctiprofile -
SCH55700 - asthma.
-
Mauser PJ, Pitman A, Witt A, et al. Inhibitory effect of the TRFK-5 anti-IL-5 antibody in a guinea pig model of asthma. Am-Rev-Respir-Dis 1993;1481623-1627.
PubMed -
Weinstein SF, Germinaro M, Bardin P, Korn S, Bateman ED. Efficacy of Reslizumab with Asthma, Chronic Sinusitis with Nasal Polyps and Elevated Blood Eosinophils. AAAAI-2016 2016; abstr. 283.
Available from: URL: http://www.jacionline.org/article/S0091-6749(15)02151-X/fulltext -
Maspero J, Jacobs J, Garin M. Improvements in Asthma Quality of Life Questionnaire (AQLQ) Domains with Reslizumab in Patients with Inadequately Controlled Asthma and Elevated Blood Eosinophils. AAAAI-2016 2016; abstr. 44.
Available from: URL: http://www.jacionline.org/article/S0091-6749(15)01789-3/fulltext -
Kips JC, O'Connor BJ, Langley SJ, Woodcock A, Kerstjens HAM, et al. Results of a phase I trial with SCH55700, a humanized anti-IL-5 antibody, in severe persistent asthma. Am-J-Respir-Crit-Care-Med 2000;161 (Suppl.)505.
Adis International Ltd. Part of Springer Science+Business Media
© Springer Nature Switzerland AG