GSK presents data at AAAAI on efficacy of Nucala® (mepolizumab) in severe asthma patients stratified by eosinophil levels

Issued: London

GlaxoSmithKline plc (LSE/NYSE: GSK) today presented results at the American Academy of Allergy, Asthma & Immunology (AAAAI) annual meeting from a post-hoc study which showed that severe asthma patients with a baseline blood eosinophil count of 150 cells/μL or above who received Nucala® (100mg fixed dose subcutaneous injection of mepolizumab) or an investigational dose of mepolizumab had a significant improvement in their exacerbation rates compared to those receiving placebo. The data showed that when these patients were stratified by baseline eosinophil levels, a significant improvement in exacerbation rates was observed in all groups receiving mepolizumab (≥150, ≥300, ≥400, ≥500 cells/μL) with the greatest improvement occurring in those patients with higher levels of eosinophils.

These results are from a meta-analysis of data generated in 1192 patients, 846 who received mepolizumab and 346 on placebo, from the DREAM (MEA112997) and MENSA (MEA115588) studies. Overall, the meta-analysis demonstrated a 47% (95% confidence interval: 38, 56) reduction in annual exacerbation rates with mepolizumab versus placebo. Clinically relevant reductions in exacerbation rate were shown to range from 52% for patients with a baseline eosinophil threshold of 150 cells/μL or above, to 70% for patients with a baseline eosinophil threshold of 500 cells/μL or above.

Steve Yancey, Medicines Development Lead for mepolizumab, GSK said: “In a sub-set of asthma patients eosinophils drive airway inflammation. By utilising eosinophils as a biomarker, we have been able to identify those asthma patients whose disease is severe and driven by the over-expression of eosinophils and are therefore likely to respond to treatment. This post-hoc analysis confirms the predictive nature of the relationship between baseline blood eosinophil counts and efficacy outcomes in patients treated with mepolizumab.”

Eosinophils are a type of white blood cell that play a role in the development of asthma. In people with asthma, inflammatory mediators released from the eosinophil cause inflammation in the lungs increasing the risk of an exacerbation. By measuring blood eosinophil levels (a biomarker for inflammation) using a routine complete blood count, and reviewing a patient’s history of exacerbations along with their current medications, doctors are able to identify the patients who are most likely to benefit from treatment with mepolizumab. The results of the meta-analysis reinforce the relevance of a data-driven approach to determining the eosinophil cut-off levels used to identify the patient population that is appropriate for treatment with mepolizumab.

About the meta-analysis – Poster no. 677

The aim of the meta-analysis (Study ID 204664) was to assess the efficacy of mepolizumab in relation to asthma exacerbation rates in patients with severe eosinophilic asthma, based on different baseline blood eosinophil thresholds.

Individual patient data from 1192 participants from the DREAM and MENSA studies aged ≥12 years with a history of ≥2 exacerbations in the previous year were included in the meta-analysis. The study looked at all doses of mepolizumab used in the previous studies. In DREAM, patients received 75mg, 250mg or 750mg of intravenous (IV) mepolizumab or placebo every four weeks for 52 weeks. In MENSA patients received 75mg IV or 100mg subcutaneous mepolizumab or placebo every four weeks for 32 weeks.

Where licensed, Nucala is administered as a 100mg fixed dose subcutaneous injection every four weeks.

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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