FDA Accepts Application for Rare Neuromuscular Disorder Drug

Alexion Pharmaceuticals recently announced the FDA accepted the supplemental biologics license for eculizumab (Soliris) for the treatment of patients with refractory generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody-positive.

The submission included positive, comprehensive data from the phase 3 REGAIN study, and has a Prescription Drug User Fee Act data of October 23, 2017, according to a press release.

Alexion reported that patients with gMG who are AChR antibody-positive are an “ultra-rare” subset of patients. Myasthenia gravis is a chronic, progressive autoimmune neuromuscular disease where the complement system causes a harmful inflammatory effect on the neuromuscular junction, according to the press release.

The disease generally starts with weakness of the ocular muscles, and progresses to weakness of the head, neck, trunk, limbs, and respiratory system. Although many patients can be treated with current medications, 10% to 15% are resistant to treatment, and experience disease progression. Without treatment, patients can experience reduced quality of life due to slurred speech, impaired swallowing, choking, double vision, fatigue, shortness of breath, frequent hospital stays, and respiratory failure, according to Alexion.

In patients with AChR-positive disease, the immune system creates antibodies against AChR, which is used to control muscles. This leads to the destruction of the neuromuscular junction, and impairs muscle function.

In the study, investigators discovered that treatment with eculizumab reduced disease severity in patients with gMG compared with placebo at 26 weeks.

The safety profile of the drug was consistent with labeling, according to the release. Common adverse events included headache, upper respiratory tract infection, nasopharyngitis, and nausea.

Eculizumab received regulatory approval to reduce hemolysis in patients with paroxysmal nocturnal hemoglobinuria, which is a rare and life-threatening blood disease. Eculizumab is also the only drug approved to treat atypical hemolytic uremic syndrome.

If approved, eculizumab would be the first complement inhibitor for patients with AChR-positive gMG. In both the United States and the European Union, eculizumab was granted orphan drug designation. Currently, eculizumab is not approved in any country to treat patients with refractory AChR-positive gMG, according to Alexion.

“We look forward to working with the FDA to bring this potentially life-transforming treatment to patients who are in dire and urgent need of effective treatment,” said Martin Mackay, PhD, executive vice president and Global Head of R&D at Alexion. “Refractory gMG is an ultra-rare disease. Despite existing treatment options for gMG, patients with refractory gMG continue to face severe complications, including difficulty walking, talking, swallowing, and breathing normally. Exacerbations of their disease may be life-threatening and require hospitalization and intensive care.”