Mixed Results in Phase 3 Trial for Myasthenia Gravis Drug


alexion-pharmaceuticalsResults from a phase 3 trial to test eculizumab in patients with refractory generalized myasthenia gravis (MG) show that the drug did not have a statistically significant effect on the primary endpoint — the Myasthenia Gravis – Activities of Daily Living profile (MG-ADL), a patient-reported index of daily living assessment.

Alexion Pharmaceuticals, which is developing the drug for MG, reported the results June 6. Although the primary endpoint was missed, the company said, clinically meaningful improvements in several secondary measures were observed in patients treated with eculizumab compared with those who received a placebo including an improvement in the Quantitative Myasthenia Gravis (QMG) score, a physician-administered test that assesses MG severity.

Alexion reported that it is continuing to analyze the data and plans to discuss the results with regulatory agencies in the United States and Europe. It is approved in the United States, European Union, Japan and other countries for the treatment of other conditions.

Eculizumab (brand name Soliris) is a terminal complement inhibitor. A part of the immune system, the complement system helps antibodies clear damaged cells and potentially toxic microbes that could cause infections. In MG, antibodies whose job it is to target these toxic pathogens, instead inappropriately recruit the complement system and target the space across which nerve fibers transmit signals to muscle fibers, called the neuromuscular junction (NMJ). Eculizumab is thought to work in MG by inhibiting the complement pathway to prevent destruction of the neuromuscular junction.

In the REGAIN trial, participants were treated over a period of 26 weeks either with eculizumab or placebo. Those who were treated with the drug received 900 milligrams weekly for four weeks, followed by 1,200 milligrams of eculizumab one week later, and then 1,200 milligrams of eculizumab every two weeks.

Refractory generalized myasthenia gravis occurs in a subset of MG patients. It causes muscle weakness in the head, neck, trunk, limb and respiratory muscles and does not respond to treatments that are typically helpful in other patients. Profound weakness throughout the body often is accompanied by slurred speech, impaired swallowing and choking, double vision, upper and lower extremity weakness, disabling fatigue, shortness of breath due to respiratory muscle weakness, and episodes of respiratory failure. Patients with refractory generalized MG frequently require hospitalization, often involving intensive care unit stays. There are no approved therapies for this form of MG.

Although MDA was not involved in this trial, it has invested in previous research investigating complement inhibition as a therapeutic strategy for MG.