FDA Approves Expanded Use of GSK’s Nucala to Include EGPA

GlaxoSmithKline said that the U.S. Food and Drug Administration has approved Nucala as the first targeted treatment for eosinophilic granulomatosis with polyangiitis, previously known as Churg-Strauss syndrome, a chronic rare disease caused by inflammation in the wall of small-to-medium-sized blood vessels.

EGPA affects about 5,000 patients in the United States. The mean age of diagnosis is 48 years, and the disease can be life-threatening for some patients. It is characterized by asthma and can cause damage to lungs, sinuses, skin, heart, gastrointestinal tract, nerves and other organs. The most common symptoms include extreme fatigue, muscle and joint pain, weight loss, sinonasal symptoms, and breathlessness.

The current approach to disease management is primarily based on reduction of active inflammation and suppression of the immune response with corticosteroids and immunosuppressive therapy. Although the use of these treatments can be effective for establishing remission, patients remain vulnerable to either the complications of the long-term use of these therapies and to the risk of relapse, particularly if the dose of corticosteroid is reduced.

“Patients suffering from EGPA too often face a frustrating journey from a delay in receiving a proper diagnosis to having few effective treatment options with an acceptable safety profile,” said Peter Merkel, chief of the Division of Rheumatology at Perelman School of Medicine, University of Pennsylvania, and site investigator for the Nucala study. “Rheumatologists, immunologists, and pulmonologists have a significant role in properly diagnosing and treating patients with EGPA. Today’s approval of mepolizumab provides specialists with the ability to offer a targeted treatment to appropriate patients with this complex disease.”

Nucala is an interleukin-5 antagonist monoclonal antibody. The FDA first approved Nucala, also known as mepolizumab, in 2015 for severe eosinophilic asthma. It is a targeted biologic therapy developed to treat diseases that are driven by inflammation linked to higher-than-normal eosinophils in the blood. Eosinophils are a type of white blood cell. When present in the body in normal levels, eosinophils can play a role in protecting the body against infection, but over-production can cause inflammation in vital organs and tissues, sometimes permanently damaging them. GSK is also seeking approval of the drug as a treatment for Chronic obstructive pulmonary disease.

The FDA’s approval for EGPA is based on results from the pivotal, 52-week, phase 3 study, conducted as a collaboration between GSK and the National Institute of Allergy and Infectious Diseases. The study evaluated the efficacy and safety of 300mg of mepolizumab administered subcutaneously every four weeks versus placebo as add-on therapy to standard of care (corticosteroids plus or minus immunosuppressants) in 136 patients with relapsing and/or refractory EGPA. The study achieved statistical significance with mepolizumab for both co-primary endpoints of accrued time in remission and proportion of patients achieving remission at both weeks 36 and 48. Six secondary endpoints also supported approval of mepolizumab.

The most common adverse reactions associated with Nucala in clinical trials included headache, injection site reaction, back pain, and fatigue.

The FDA granted this application Priority Review and Orphan Drug designations.

December 12, 2017