Efficacy and Safety of Ravulizumab, a Long-acting Terminal Complement Inhibitor, in Adults with Anti-Acetylcholine Receptor Antibody-Positive Generalized Myasthenia Gravis: Results from the Phase 3 CHAMPION MG Study
Tuan Vu1, Andreas Meisel2, Renato Mantegazza3, Djillali Annane4, Masahisa Katsuno5, Rasha Aguzzi6, Ahmed Enayetallah6, Kathleen N. Beasley6, Nishi Rampal6, James F. Howard7
1University of South Florida, 2Charité Universitätsmedizin Berlin, 3Fondazione IRCCS Istituto Neurologico Carlo Besta, 4Hôpital Raymond Poincaré, University of Versailles, 5Nagoya University Graduate School of Medicine, 6Alexion, AstraZeneca Rare Disease, 7The University of North Carolina
Objective:

To evaluate the efficacy and safety of ravulizumab in adults with anti-acetylcholine receptor antibody-positive (AChR Ab+) generalized myasthenia gravis (gMG).

Background:

Ravulizumab is a potent terminal complement C5 inhibitor. Engineered to have a long half-life that permits a maintenance dosing interval of 8 weeks, ravulizumab is a convenient treatment option.

Design/Methods:

In this multicenter, double-blind, phase 3 study (NCT03920293), adults with AChR Ab+ gMG (Myasthenia Gravis Foundation of America Class II–IV) and Myasthenia Gravis-Activities of Daily Living (MG-ADL) score ≥6 were randomized (1:1) to receive intravenous ravulizumab infusion (body weight-based dose regimen: 2400–3000 mg loading dose on Day 1, then 3000–3600 mg every 8 weeks beginning on Day 15) or placebo for 26 weeks. Stable standard-of-care therapy was permitted throughout the study. The primary efficacy endpoint was change from baseline to Week 26 in MG-ADL total score. Secondary endpoints included change from baseline in Quantitative Myasthenia Gravis (QMG) total score.

Results:

In total 175 patients were enrolled from 85 centers worldwide. Treatment with ravulizumab was associated with a statistically significant improvement in MG-ADL total score at Week 26 (-3.1 vs -1.4 for placebo; p<0.001). Ravulizumab also demonstrated statistically significant improvements from baseline through Week 26 in QMG total score (-2.8 vs -0.8 for placebo;  p<0.001). Improvements in MG-ADL and QMG scores were observed within 1 week, with maintenance of benefit through Week 26. No notable differences in adverse events were observed between treatment groups.

Conclusions:

Ravulizumab, administered every 8 weeks, provided rapid and sustained improvement in symptoms and was well tolerated in adult patients with AChR Ab+ gMG.