Alexion Pharmaceuticals has submitted an application to Japan’s Ministry of Labour and Welfare (MHLW) to extend the indication for Soliris (eculizumab) as a potential treatment for patients with refractory generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody-positive. The submission is supported by comprehensive data from the phase 3 REGAIN study.

“We look forward to working with the Japanese health authorities to bring this potentially life-transforming treatment to patients in Japan who are suffering and in urgent need of an effective therapy,” said Martin Mackay, Ph.D., executive vice president and global head of R&D at Alexion. “If approved, Soliris could be a critical step toward improving the lives of patients with refractory gMG.”

Patients with AChR-positive refractory gMG represent an ultra-rare population. Despite existing treatment options for gMG, these patients 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.

If approved, Soliris would be the first and only complement inhibitor for patients with refractory AChR-positive gMG in Japan. Alexion has also submitted marketing applications in the U.S. and EU to extend the indication for Soliris as a potential treatment for patients with refractory gMG who are AChR-positive, which have been accepted by the US Food and Drug Administration (FDA) and validated by the European Medicines Agency (EMA). Soliris has received Orphan Drug Designation (ODD) for the treatment of patients with MG in the US and EU, and for treatment of patients with refractory gMG in Japan. Soliris is not approved in any country for the treatment of patients with refractory AChR-positive gMG.

Refractory generalized myasthenia gravis (gMG) patients who are anti-acetylcholine receptor (AChR) antibody-positive represent an ultra-rare segment of patients with MG—a chronic, debilitating and progressive autoimmune neuromuscular disease where the complement system mediates a progressive, destructive inflammatory effect on the neuromuscular junction. Patients with refractory AChR-positive gMG experience severe morbidities and life-threatening complications despite currently available MG therapies.

MG typically begins with weakness in the ocular muscles and often progresses to the more severe and generalized form, known as gMG, to include weakness of the head, neck, trunk, limb and respiratory muscles. While most symptoms in patients with gMG are managed with conventional therapies, 10% to 15% of patients are considered refractory—meaning they do not respond to multiple conventional therapies and continue to suffer profound muscle weakness throughout the body that can result in slurred speech, impaired swallowing and choking, double vision, disabling fatigue, shortness of breath due to respiratory muscle weakness, immobility requiring assistance, frequent hospital and intensive care unit admissions with prolonged stays, and periods of respiratory failure.

In patients with AChR-positive MG, the body’s own immune system turns on itself to produce antibodies against AChR, a receptor located on muscle cells in the neuromuscular junction (NMJ) and used by nerve cells to communicate with the muscles these nerves control. The binding of these antibodies to AChR activates the complement cascade which leads to the destruction of the NMJ. As a result, the communication between nerve and muscle is disrupted, which leads to a loss of normal muscle function.