Positive topline results were announced from a phase 3 study evaluating the efficacy and safety of ravulizumab-cwvz in adults with generalized myasthenia gravis.
The global, multicenter, randomized, double-blind, placebo-controlled study (ClinicalTrials.gov Identifier: NCT03920293) included 175 adults with generalized myasthenia gravis who were not previously treated with a complement inhibitor. Patients were randomly assigned 1:1 to receive either ravulizumab-cwvz or placebo via intravenous infusion as a single weight-based loading dose on day 1, followed by regular weight-based maintenance dosing beginning on day 15 every 8 weeks for 26 weeks.
The primary endpoint was the change from baseline in the Myasthenia Gravis-Activities of Daily Living Profile (MG-ADL) total score at week 26. Key secondary endpoints included the change from baseline through week 26 in the Quantitative Myasthenia Gravis (QMG) total score and the proportion of patients who had an improvement of at least 5 points in QMG total score.
Findings showed that treatment with ravulizumab-cwvz was associated with a statistically significant change in MG-ADL score at week 26 (-3.1 vs -1.4 for placebo; treatment difference -1.6; P <.001). Ravulizumab-cwvz also demonstrated clinically meaningful and statistically significant improvements from baseline through week 26 in the QMG total score (P <.001). Thirty percent of patients treated with ravulizumab-cwvz had an improvement of at least 5 points in QMG total score compared with 11.3% of those who received placebo (P =.005). Improvements in MG-ADL and QMG scores were observed as early as week 1 and sustained through week 26.
The study did not meet statistical significance for other secondary endpoints, including the change from baseline on the Revised 15-Component Myasthenia Gravis Quality of Life (MG-QOL15r) score and the Neuro-QOL Fatigue score.
Upon completion of the 26-week study, patients were eligible to enroll in an ongoing open-label extension period evaluating ravulizumab-cwvz for up to 2 years. At a preliminary analysis of the open-label extension period, 75 patients had completed an additional 26 weeks of treatment for a total of 52 weeks.
Results showed that treatment effects of ravulizumab-cwvz were maintained through the additional 26 weeks. Patients who previously received placebo and switched to ravulizumab-cwvz at the beginning of the open-label period achieved immediate and sustained improvement in MG-ADL and QMG scores.
As for safety, adverse events were observed to be comparable between the ravulizumab-cwvz and placebo treatment arms. The most frequently reported adverse events for ravulizumab-cwvz and placebo, respectively, were headache (18.6% vs 25.8%), diarrhea (15.1% vs 12.4%), and nausea (10.5% vs 10.1%).
Ravulizumab-cwvz, a complement inhibitor, is marketed under the trade name Ultomiris and is currently approved for the treatment of paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome to inhibit complement-mediated thrombotic microangiopathy.
The Company plans to submit regulatory applications for the myasthenia gravis indication in late 2021/early 2022.
Alexion announces positive topline results from phase 3 study of Ultomiris® (ravulizumab-cwvz) in adults with generalized myasthenia gravis (gMG). News release. Alexion Pharmaceuticals. Accessed July 15, 2021. https://www.businesswire.com/news/home/20210715006015/en/Alexion-Announces-Positive-Topline-Results-from-Phase-3-Study-of-ULTOMIRIS%C2%AE-ravulizumab-cwvz-in-Adults-with-Generalized-Myasthenia-Gravis-gMG