FDA Grants Orphan Drug Status to Alexion's Soliris For Myasthenia Gravis

By Cyndi Root

Alexion Pharmaceuticals announced in a press release that the Food and Drug Administration (FDA) granted Orphan Drug Designation (ODD) to Soliris (eculizumab) for Myasthenia Gravis (MG). Patients with MG experience a disabling neurologic disorder caused by uncontrolled complement activation due to antibodies directed at the neuromuscular junction. Martin Mackay, Ph.D., Executive Vice President, Global Head of R&D at Alexion, said, “By specifically inhibiting the terminal complement pathway, which is believed to play a pivotal role in the pathophysiology of MG, we believe that eculizumab has the potential to help patients living with this devastating rare disorder.”

Soliris

Alexion developed and commercialized Soliris. It was approved in the U.S. and the European Union in 2007 and in Japan in 2010 for paroxysmal nocturnal hemoglobinuria (PNH), a blood disorder characterized by the destruction of red blood cells. Soliris was approved in the U.S., the European Union, and Japan in 2013 for atypical hemolytic uremic syndrome (aHUS), which is characterized by blood clots in small vessels. Those two conditions are also caused by uncontrolled complement activation. Soliris (eculizumab) is terminal complement inhibitor. Because Soliris blocks terminal complement pathway activation, patients face increased incidence of infections, especially bacterial infections, and Soliris should not be used with patients who have a systemic infection.

Soliris Clinical Trials

Currently, Alexion is registering patients for a placebo-controlled trial of Soliris in patients with refractory generalized MG. The multinational trial is titled, “Safety and Efficacy of Eculizumab in Refractory Generalized Myasthenia Gravis.” The study started in 2013 and is expected to finish in 2016. Investigators are studying the effects of Soliris on 92 MG patients. The primary endpoints are a change in total MG-ADL score (at the end of study, week 26/visit 17) and a change from baseline in the MG-ADL total score at week 26 for eculizumab as compared to placebo. Secondary endpoints are overall safety and tolerability of eculizumab, adverse events, vital signs, laboratory assessments, physical exams, and ECGs.

Myasthenia Gravis  

MG is a neurologic disorder in the nerve-muscle junction caused by auto-antibodies. The resulting terminal complement activation causes signaling deficits between nerve and muscle fibers. The tissue damage causes weakness in the eye muscles progressing to weakness in large motor muscles. Patients may have difficulty talking, chewing, and swallowing. Respiratory failures can lead to life-threatening myasthenic crisis.