Alexion Pharmaceuticals announced positive topline results from a Phase 3 study evaluating the safety and efficacy of Ultomiris (ravulizumab-cwvz) in adults with generalized myasthenia gravis (gMG). The study met its primary endpoint of change from baseline in the Myasthenia Gravis-Activities of Daily Living Profile (MG-ADL) total score, a patient-reported assessment, at Week 26 with high statistical significance.
This global Phase 3 randomized, double-blind, placebo-controlled, multicenter 26-week study evaluated 175 adults with gMG who were not previously treated with a complement inhibitor medicine. Patients were enrolled across North America, Europe, Asia-Pacific and Japan. Patients were randomized 1:1 to receive Ultomiris or placebo for a total of 26 weeks. Patients received a single weight-based loading dose on Day 1, followed by regular weight-based maintenance dosing beginning on Day 15, every 8 weeks. The primary endpoint of change from baseline in the Myasthenia Gravis-Activities of Daily Living Profile (MG-ADL) total score at Week 26 was assessed along with multiple secondary endpoints evaluating improvement in disease-related and quality of life measures.
The study met its primary endpoint, with a statistically significant change in MG-ADL score from baseline through Week 26 for patients receiving Ultomiris compared to those receiving placebo (Ultomiris: -3.1, placebo: -1.4, treatment difference: -1.6). In the prospectively-defined secondary endpoints of change from baseline through Week 26 in Quantitative Myasthenia Gravis (QMG) total score – a physician-administered assessment of MG clinical severity – as well as the proportion of patients who achieved an improvement of at least 5 points in QMG, Ultomiris also demonstrated clinically meaningful and statistically significant improvements. Nearly three times as many patients receiving Ultomiris experienced an improvement of at least 5 points in their QMG score compared to patients receiving placebo (30.0% vs 11.3%). These improvements in MG-ADL and QMG scores were observed as early as Week 1 and were sustained through Week 26. The most common adverse effects were headache, nausea and diarrhea.
Based on these results, Alexion plans to make regulatory filings in the U.S., European Union and Japan in late 2021/early 2022.
Ultomiris (ravulizumab) is a long-acting C5 complement inhibitor. It works by inhibiting the C5 protein in the terminal complement cascade, a part of the body’s immune system. When activated in an uncontrolled manner, the complement cascade over-responds, leading the body to attack its own healthy cells.
About Generalized myasthenia gravis (gMG)
gMG is a rare autoimmune disorder characterized by severe muscle weakness. In gMG, inflammation causes damage at the connection point between nerve cells and the muscles they control (known as the neuromuscular junction or NMJ). This damage leads to a breakdown of communication between the brain and muscles, causing loss of muscle function and severe weakness. About 85 percent of people with gMG produce specific antibodies that bind to the surface of the cells at the NMJ. This binding activates the complement cascade and causes the immune system to attack the NMJ. People with gMG can suffer from initial symptoms, such as slurred speech, droopy eyelids, double vision, and lack of balance, which can often lead to more severe symptoms like choking, impaired swallowing, extreme fatigue and even episodes of respiratory failure.