GSK presents new data on the long-term efficacy & safety of Nucala® for the treatment of severe asthma with an eosinophilic phenotype

05 March 2016
Issued: London

GlaxoSmithKline plc (LSE/NYSE: GSK) today presented new safety and efficacy data for Nucala® (mepolizumab) from the open-label COSMOS (MEA115661) study at the American Academy of Allergy, Asthma & Immunology annual meeting. The data shows that the risk/benefit profile generated through the pivotal studies for Nucala was maintained over an extended 52-week period. Exacerbation risk reduction, asthma control improvement and oral corticosteroid dose reduction seen in earlier trials was also demonstrated in the study.

A total of 651 patients participated in the COSMOS study. Of these patients, 414 had received mepolizumab in either the 32-week phase III MENSA (MEA115588) exacerbation study or the 24-week SIRIUS (MEA115575) steroid-reduction study, providing up to 84 weeks of on-treatment safety and efficacy data. The study also included 237 patients who had received placebo in the previous phase III trials. For patients switching from placebo to mepolizumab, findings from COSMOS showed similar improvements in asthma control to those in the mepolizumab arms of the previous studies.

Frank Albers, Global Medical Affairs Lead for Nucala, GSK said: "Severe asthma with an eosinophilic phenotype is a chronic condition that affects a small, but significant, number of patients who need to take multiple medications to control their day-to-day symptoms and reduce the risk of frequent and serious asthma attacks. As a first-in-class anti-IL-5 biologic therapy, Nucala was specifically developed for these difficult-to-treat patients. Results from COSMOS support the long-term safety profile and durability of response for Nucala and further our understanding of this novel therapeutic approach."

Study findings
The primary objective of the study was to describe the safety profile of long-term mepolizumab treatment. Findings from COSMOS showed that the safety profile of mepolizumab was similar to that reported in the previous Phase III randomised studies. The most frequently reported adverse events during the treatment period were nasal congestion (30%), upper respiratory tract infection (16%), asthma (worsening/exacerbation) (14%), and headache (14%).

The secondary objective of the study was to evaluate the effect of long-term dosing on clinical markers of asthma control. In patients continuing mepolizumab from the MENSA trial, exacerbation rates per year remained consistent with the pivotal studies – the exacerbation rate was 0.91 exacerbations per year at the end of MENSA and 0.92 per year at the end of the combined 84-week period. Improvements in asthma control, measured by the Asthma Control Questionnaire-5 (ACQ-5) score, seen in earlier trials were also maintained. For patients previously treated with placebo, their risk of an exacerbation was nearly halved when they switched to mepolizumab, decreasing over time from 1.94 per year to 1.04 per year, which was consistent with previous data. In addition, ACQ-5 scores improved by 0.30 points by week 4 compared to baseline (where a minimal clinically important change is 0.50 points) and the change maintained through to week 52 for patients previously treated with placebo.

A post-hoc analysis evaluated the durability of steroid reduction following open-label mepolizumab treatment among the sub-set of subjects from the SIRIUS study that completed COSMOS. The impact of mepolizumab on oral corticosteroid dose seen in SIRIUS was consistent with that seen in COSMOS. For patients who continued treatment with mepolizumab, the median oral corticosteroid dose was maintained at 2.5mg/day, having been reduced from 10mg at the start of the SIRIUS study. Patients switching to mepolizumab from placebo in SIRIUS demonstrated reductions in oral corticosteroid similar to those seen in the previous trial, reducing their steroid dose by 50%, from a median dose of 10mg/day down to 5mg/day. In contrast to the SIRIUS study, the COSMOS study did not require physicians to follow an oral corticosteroid reduction protocol with a formal step-down algorithm. However, reductions in oral corticosteroid dose were achieved in COSMOS and were accompanied by consistent reductions in exacerbation rate and improvements in symptom control.

About the COSMOS study (MEA115661) – Poster no. 43 & 49
A total of 651 patients were enrolled in the study and received mepolizumab 100mg subcutaneously once every four weeks for 52 weeks. Patients remained on their current standard of care asthma therapy throughout the study. All patients had previously completed either the MENSA or SIRIUS studies, with 414 patients having received mepolizumab in the prior studies (the remaining 237 patients had been randomised to placebo in their previous study). All participants in the MENSA and SIRIUS trials had severe asthma with peripheral blood eosinophil levels greater than or equal to 150 cells/μL at initiation of treatment or greater than or equal to 300 cells/μL within the past 12 months.

All participants in COSMOS received a 100mg dose of mepolizumab subcutaneously every four weeks in addition to their standard of care respiratory medications. This is the same dose and administration regimen for which mepolizumab is licensed, under the brand name Nucala.

The summary results of study MEA115661 are available on the GSK clinical study register.

Additional GSK severe asthma and mepolizumab poster presentations at American Academy of Allergy, Asthma & Immunology annual meeting 2016

Comparative effectiveness of mepolizumab and omalizumab in severe asthma: An indirect comparison – Poster no. 271
Exacerbation reduction in severe eosinophilic asthma based on eosinophil thresholds – Poster no. 677
The identification and description of severe asthma patients in a cross-sectional study (the IDEAL Study) – Poster no. 335
About asthma
Current estimates indicate that as many as 242 million people live with asthma worldwide. For many of these patients, existing therapies can provide adequate control of their symptoms if used appropriately. However, up to 5% of patients with asthma have difficulty in achieving symptom control with existing therapies.

About severe asthma and eosinophilic inflammation
Severe asthma is defined as asthma which requires treatment with high dose inhaled corticosteroids (ICS) plus a second controller (and/or systemic corticosteroids) to prevent it from becoming 'uncontrolled' or which remains 'uncontrolled' despite this therapy. Severe asthma patients are also often categorised by long-term use of oral corticosteroids (OCS). In a sub-set of severe asthma patients, the over-production of eosinophils (a type of white blood cell) is known to cause inflammation in the lungs that can affect the airways, limiting breathing and increasing the frequency of asthma attacks. Interleukin-5 (IL-5) is the main promoter of eosinophil growth, activation and survival and provides an essential signal for the movement of eosinophils from the bone marrow into the lung. Studies suggest that approximately 60% of patients with severe asthma have eosinophilic airway inflammation.

About Nucala
Nucala is a monoclonal antibody that binds to IL-5, preventing it from binding to its receptor on the surface of eosinophils. Inhibiting IL-5 binding in this way reduces blood, tissue and sputum eosinophil levels.

In the US Nucala is licensed as an add-on maintenance treatment for patients with severe asthma aged 12 years and older, and with an eosinophilic phenotype. Nucala is not approved for the treatment of other eosinophilic conditions or relief of acute bronchospasm or status asthmaticus. Full US Prescribing Information is available at US Prescribing Information Nucala.

In the EU Nucala is licensed as an add-on treatment for severe refractory eosinophilic asthma in adult patients. For the EU Summary of Product Characteristics for Nucala, please visit: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003860/WC500198037.pdf

Nucala has also been approved in Canada and Australia. Further regulatory applications have been submitted and are under review in other countries.

Nucala® is a registered trade mark of the GSK group of companies.

Important safety information for Nucala

The following information is taken from the highlights section of the US Prescribing Information for Nucala.

Contraindications:

History of hypersensitivity to mepolizumab or excipients in the formulation.
Warnings and precautions:

Hypersensitivity reactions (e.g., angioedema, bronchospasm, hypotension, urticaria, rash) have occurred after administration of Nucala. Discontinue Nucala in the event of a hypersensitivity reaction.
Do not use to treat acute bronchospasm or status asthmaticus.
Herpes zoster infections have occurred in patients receiving Nucala. Consider varicella vaccination if medically appropriate prior to starting therapy with Nucala.
Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of therapy with Nucala. Decrease corticosteroids gradually, if appropriate.
Treat patients with pre-existing helminth infections before therapy with Nucala. If patients become infected while receiving treatment with Nucala and do not respond to anti-helminth treatment, discontinue Nucala until parasitic infection resolves.
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