Alexion to Present Long-Term Data of Experimental C5 Inhibitor in gMG

Rare Daily Staff

Alexion, AstraZeneca Rare Disease, said new data on its experimental treatment gefurulimab for generalized myasthenia gravis suggest that weekly, self-administered injections may provide sustained symptom control for adults with a common antibody-driven form of the rare autoimmune disease.

The company will present the long-term clinical-trial findings at the upcoming American Association of Neuromuscular & Electrodiagnostic Medicine Annual Meeting and the Myasthenia Gravis Foundation of America Scientific Session, to be held Sept. 29 through Oct. 2.

Myasthenia gravis is a chronic autoimmune disease that disrupts communication between nerves and muscles. It can cause muscles to weaken and tire easily, leading to symptoms such as drooping eyelids, double vision, difficulty speaking, chewing, or swallowing, and weakness in the arms and legs. In severe cases, people with the condition can also have trouble breathing.

Generalized myasthenia gravis, or gMG, affects muscles beyond those controlling the eyes and can be unpredictable. Symptoms may worsen suddenly, sometimes resulting in a myasthenic crisis that requires urgent medical care and breathing support.

Many people with gMG have antibodies against the acetylcholine receptor, a protein at the neuromuscular junction, where nerves signal muscles to contract. These antibodies can activate part of the immune system known as complement, damaging the connection between nerves and muscles and contributing to weakness.

Gefurulimab is an experimental treatment designed to block complement component 5, or C5, a protein involved in the immune pathway that can drive damage at the neuromuscular junction in some people with gMG.

Unlike complement medicines administered by intravenous infusion, gefurulimab is intended to be injected under the skin once a week by patients themselves. The potential for at-home, self-administered treatment could reduce the need for regular clinic or infusion-center visits, although the medicine has not yet been approved and its benefits and risks remain under regulatory review.

The treatment is a dual-binding nanobody, a smaller antibody-based protein engineered to bind C5 at two sites. Alexion is studying it in adults with generalized myasthenia gravis who have anti-acetylcholine receptor antibodies.

The new findings come from the open-label extension of the Phase 3 PREVAIL trial. In an open-label extension, participants generally know which treatment they are receiving, and patients who previously received placebo may be allowed to begin receiving the active medicine.

According to Alexion, people who received gefurulimab during the main study maintained improvements through 52 weeks on three measures of myasthenia gravis symptoms and function. At week 52, the average change from baseline was -5.3 points on the Myasthenia Gravis Activities of Daily Living score, -5.3 points on the Quantitative Myasthenia Gravis score, and -9.4 points on the Myasthenia Gravis Composite score.

Participants who switched from placebo to gefurulimab at week 26 also showed improvements after beginning treatment, which were sustained through week 52.

Alexion said a separate analysis found that some patients responded as early as week 1 and maintained minimal symptom expression through week 52. The company also plans to present an analysis suggesting that gefurulimab reduced gMG-related hospitalizations and use of rescue therapy through week 26, compared with placebo.

The company said gefurulimab was well tolerated in the extension study and that no meningococcal infections were reported. Because C5 inhibitors can increase vulnerability to serious meningococcal infection, patients receiving medicines in this class generally require vaccination and careful monitoring.