By PPN News Staff

The FDA expanded the approved use of mepolizumab (Nucala, GlaxoSmithKline) to treat adult patients with eosinophilic granulomatosis with polyangiitis (EGPA), a rare autoimmune disease that causes vasculitis. This new indication provides the first FDA-approved therapy specifically to treat EGPA.

EGPA (formerly known as Churg-Strauss syndrome) is a condition characterized by asthma, high levels of eosinophils and inflammation of small- to medium-sized blood vessels. The inflamed vessels can affect various organ systems, including the lungs, gastrointestinal tract, skin, heart and nervous system. It is estimated that 0.11 to 2.66 cases per 1 million people are newly diagnosed each year, with an overall prevalence of 10.7 to 14 per million adults, according to the National Institutes of Health.

The current approach to disease management is primarily based on reduction of active inflammation and suppression of the immune response through the use of corticosteroids and concomitant immunosuppressive therapy (e.g., methotrexate, azathioprine, mycophenolate mofetil), and/or cytotoxic agents (e.g. cyclophosphamide). Although these treatments can be effective for establishing remission, patients remain vulnerable to complications of the long-term use of these therapies and to the risk for relapse, particularly if the dose of the corticosteroid is reduced.

Mepolizumab is an interleukin-5 antagonist, monoclonal antibody (IgG1 kappa) produced by recombinant DNA technology in Chinese hamster ovary cells. It is administered once every four weeks by subcutaneous injection by a health care professional into the upper arm, thigh or abdomen.

The new indication was based on results from the pivotal 52-week, phase 3 MIRRA trial, conducted as a collaboration between GSK and the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health (N Engl J Med  2017;376:1921-1932).

The MIRRA study evaluated the efficacy and safety of 300 mg of mepolizumab administered subcutaneously every four weeks versus placebo as add-on therapy to standard of care (corticosteroids with or without immunosuppressants) in 136 patients with relapsing and/or refractory EGPA. Both co-primary end points (accrued time in remission and proportion of patients achieving remission at both weeks 36 and 48) were statistically significantly in favor of mepolizumab. All six secondary end points (involving relapse, remission and corticosteroid use) were significantly better with mepolizumab. 

The percentage of patients experiencing on-treatment adverse events was similar in the two treatment groups (mepolizumab, 97%; placebo, 94%). Injection site reactions (e.g., pain, erythema, swelling) occurred at a rate of 15% in patients receiving mepolizumab and 13% in those receiving placebo. Serious adverse events were reported by 18% of patients receiving mepolizumab compared with 26% of the placebo group, with the most frequently reported condition being asthma worsening/exacerbation (3% vs. 6%). The most common adverse reactions associated with mepolizumab in clinical trials included headache, injection site reaction, back pain and fatigue.

“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. Rheumatologists, immunologists and pulmonologists have an important 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,” Peter A. Merkel, MD, chief of the Division of Rheumatology at Perelman School of Medicine, University of Pennsylvania, and MIRRA study site investigator said.

Mepolizumab should not be administered to patients who have a history of hypersensitivity to mepolizumab or one of its ingredients. It should not be used to treat acute bronchospasm or status asthmaticus. Hypersensitivity reactions, including anaphylaxis, angioedema, bronchospasm, hypotension, urticaria and rash, have occurred. Patients should discontinue treatment if a hypersensitivity reaction occurs. Patients should not discontinue systemic or inhaled corticosteroids abruptly upon beginning treatment with mepolizumab. Instead, patients should decrease corticosteroid use gradually, if appropriate.

For full prescribing information, click here.

Health care providers should treat patients with preexisting helminthic infections before treating with mepolizumab because it is unknown if Nucala would affect patients’ responses against parasitic infections. In addition, herpes zoster infections have occurred in patients receiving mepolizumab. Health care providers should consider vaccination if medically appropriate.

The FDA granted this application priority review and orphan drug designations. Nucala was approved in 2015 to treat patients 12 years of age and older with severe asthma with an eosinophilic phenotype despite receiving their current asthma medicines.

The product is already available in the United States.