Alexion Pharmaceuticals announced yesterday that the European Commission (EC) expanded the indication of eculizumab (brand name Soliris), which already is approved to treat other conditions, to include the treatment of refractory generalized myasthenia gravis (MG) in adults who are anti-acetylcholine receptor antibody-positive. Soliris is the first and only complement-based therapy approved in the European Union for this ultra-rare subset of patients.
In the United States, the U.S. Food and drug administration currently is reviewing Soliris for the treatment of refractory generalized MG. An FDA decision on the drug is expected on or before Oct. 23, 2017.
Alexion completed submission of its marketing application for Soliris in the U.S. in January 2017. If approved, Soliris could address a significant unmet need for patients with refractory generalized MG who have largely exhausted conventional therapy.
Soliris targets the complement system
In patients with anti-acetylcholine receptor antibody-positive MG, the body’s own immune system turns on itself to produce antibodies against the acetylcholine receptor. (Acetylcholine receptors are located on muscle cells in the neuromuscular junction, or NMJ, and are used by nerve cells to communicate with the muscles these nerves control.) The binding of antibodies to acetylcholine receptors activates the complement cascade, another part of the immune system, which is responsible for helping antibodies clear damaged cells and potentially toxic microbes that could cause infections.
The activation of the complement cascade leads to a localized destruction of the NMJ. As a result, the communication between nerve and muscle is impaired, which in turn leads to a loss of normal muscle function.
A terminal complement inhibitor, Soliris is thought to work in MG by inhibiting the complement pathway to prevent destruction of the neuromuscular junction.
Refractory generalized MG affects a small segment of MG patients
Refractory generalized MG occurs in a small 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.
People with refractory generalized MG frequently require hospitalization, often involving intensive care unit stays.
REGAIN clinical trial showed mixed results
The basis of support for Soliris to treat MG comes from comprehensive data from the phase 3 REGAIN study, which tested Soliris in patients with refractory generalized MG.
Results from this study, reported in June 2016, showed 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.
However, although the primary endpoint was missed, clinically meaningful improvements in several secondary measures were observed in patients treated with Soliris 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.
Although MDA was not involved in the development and testing of Soliris, it has invested in previous research investigating complement inhibition as a therapeutic strategy for MG and is currently funding studies aiming to develop improved complement inhibitor drugs for MG.