GSK announces outcome of US FDA Advisory Committee recommending approval of mepolizumab for the treatment of adults with severe asthma

Issued: London UK

GlaxoSmithKline plc (LSE: GSK) today announced the outcome of the meeting of the Pulmonary Allergy Drugs Advisory Committee of the United States (US) Food and Drug Administration (FDA) regarding the Biologics Licence Application (BLA) for mepolizumab as an add-on maintenance treatment for severe asthma with eosinophilic inflammation.

The FDA Advisory Committee voted unanimously (14 yes, 0 no) that the efficacy and safety data for mepolizumab, an anti IL-5 monoclonal antibody delivered as a 100mg fixed dose via a subcutaneous injection every four weeks, supported approval in adults 18 years of age and older with severe asthma. The Committee also voted that the efficacy data provided substantial evidence of a clinically meaningful benefit in this population (14 yes, 0 no) and safety in adults with severe asthma had been adequately demonstrated (13 yes, 1 no).

The Committee voted against approval of mepolizumab for use in adolescents 12-17 years of age with severe asthma (4 yes, 10 no). The Committee voted that the efficacy (5 yes, 9 no) and safety (2 yes, 12 no) of mepolizumab had not been adequately demonstrated primarily due to the limited number of patients in the 12-17 age group in the overall database.   It recommended that further data are needed in this sub-population where there is a high unmet need.

Patrick Vallance, President, Pharmaceuticals R&D, said: “Our clinical development programme has demonstrated the potential of mepolizumab as a targeted treatment for difficult to treat adults with severe asthma, many of whom have been struggling to live with their condition for many years.  These are patients who currently have very few treatment options and our belief in this medicine as a new treatment option has today been reinforced by the Advisory Committee’s decision. GSK will continue to work closely with the FDA to complete the review of the BLA for mepolizumab.”

The BLA for mepolizumabwas submitted to the FDA in November 2014 for approval as an add-on maintenance treatment for patients with severe asthma with eosinophilic inflammation, identified by a blood eosinophil count of at least 150 cells per microlitre at the start of treatment or 300 cells per microlitre in the past 12 months.

FDA Advisory Committees provide non-binding recommendations for consideration by the FDA, with the final decision on approval made by the FDA. The Prescription Drug User Fee Act (PDUFA) goal date for mepolizumab is 4 November 2015.

Mepolizumab is not currently approved for use anywhere in the world. Regulatory filings in a number of other countries, including the EU and Japan, are underway. Further submissions are planned during the course of 2015.

Safety Information

In the pivotal studies of mepolizumab, the overall adverse event profile was similar between those patients receiving mepolizumab and patients receiving standard of care. The most commonly reported adverse events were headache, nasopharyngitis, bronchitis, sinusitis, fatigue and asthma. Local injection site reactions were higher in patients receiving mepolizumab subcutaneously, but were normally transient and not considered as severe.  No events of anaphylaxis were attributed to mepolizumab. 

The mepolizumab Phases II-III clinical development programme involved over 1,500 patients and comprised 9 studies.

About asthma

Currently the World Health Organization estimates that as many as 235 million people live with asthma worldwide. For many of these patients existing therapies can provide adequate control of their symptoms if used appropriately. However approximately 5% of patients with severe asthma cannot achieve symptom control with existing therapies.

About severe asthma and eosinophil 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 exacerbations. 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.

About mepolizumab

Mepolizumab is an investigational monoclonal antibody, which stops IL-5 from binding to its receptor on the surface of eosinophils. Inhibiting IL-5 binding in this way reduces blood, tissue and sputum eosinophil levels.