Rabu, 13 Desember 2017

FDA OKs Drug for Eosinophilic Granulomatosis With Polyangiitis

FDA OKs Drug for Eosinophilic Granulomatosis With Polyangiitis


The US Food and Drug Administration (FDA) has expanded the use of mepolizumab (Nucala, GlaxoSmithKline) to adults who have eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome.

Mepolizumab was first approved in 2015 for patients age 12 years and older with severe asthma with an eosinophilic phenotype.  

EGPA is a rare autoimmune disease that causes vasculitis, which can be life-threatening in some patients. The National Institutes of Health estimates that about 0.11 to 2.66 new cases per 1 million people are diagnosed each year, with an overall prevalence of 10.7 to 14 per 1 million adults. The average age at diagnosis is 48 years.

Mepolizumab, an interleukin-5 antagonist, is the first FDA-approved therapy specifically for EGPA. It is administered once every 4 weeks by subcutaneous injection into the upper arm, thigh, or abdomen.

Until now, patients with this “challenging, rare disease did not have an FDA-approved treatment option,” said Badrul Chowdhury, MD, PhD, director of the Division of Pulmonary, Allergy, and Rheumatology Products in the FDA’s Center for Drug Evaluation and Research, said in an FDA news release. “The expanded indication of Nucala meets a critical, unmet need for EGPA patients. It’s notable that patients taking Nucala in clinical trials reported a significant improvement in their symptoms.”

Mepolizumab for EGPA had orphan drug status and received priority review.

The safety and efficacy of mepolizumab for EGPA were demonstrated in a 52-week placebo-controlled trial known as MIRRA. In the trial, 136 patients with relapsing and/or refractory EGPA received 300 mg mepolizumab or placebo administered subcutaneously once every 4 weeks on top of stable daily oral corticosteroid (OCS) therapy. Starting at week 4, OCS therapy was tapered during the treatment period.

Both co-primary endpoints (accrued time in remission and proportion of patients achieving remission at weeks 36 and 48) were statistically significant in favor of mepolizumab, the company notes in a news release. The trial also met key secondary endpoints investigating relapse, remission, and corticosteroid use.

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

In the company news release, Peter A. Merkel, MD, chief of the rheumatology division at University of Pennsylvania Perelman School of Medicine, Philadelphia, and MIRRA study site investigator, said, “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.”

“Patients with EGPA often suffer from recurrent relapses that place them at greater risk of permanent tissue and organ damage,” added Michael E. Wechsler, MD, from National Jewish Health in Denver, Colorado, and principal investigator of the MIRRA study. “Clinical data demonstrated that mepolizumab increased accrued time in remission, reduced the frequency of relapse and flares, and enabled patients to have their dose of corticosteroid reduced compared to placebo in patients already receiving standard of care. These are key treatment goals and this approval is an important milestone both for treating physicians and for patients.”

The FDA notes that mepolizumab is contraindicated in patients with a history of hypersensitivity to mepolizumab or one of its ingredients. Mepolizumab is not approved for the treatment of other eosinophilic conditions or relief of acute bronchospasm or status asthmaticus. Hypersensitivity reactions, including anaphylaxis, angioedema, bronchospasm, hypotension, urticaria, and rash, have occurred. Patients should discontinue treatment in the event of a hypersensitivity reaction.

Patients should not stop systemic or inhaled corticosteroids abruptly when starting mepolizumab but rather decrease corticosteroids gradually, if appropriate, the FDA said.

Pre-existing helminth infections should be treated before starting mepolizumab because it is unknown whether the drug would affect patients’ responses against parasitic infections. In addition, herpes zoster infections have occurred in patients receiving mepolizumab. Healthcare providers should consider vaccination if medically appropriate.

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