Efficacy and safety of ravulizumab in anti-acetylcholine receptor antibody-positive generalized myasthenia gravis: phase 3 CHAMPION MG study

Topic:

Clinical Trials

Poster Number: 68

Author(s):

Tuan Vu, MD, University of South Florida, Andreas Meisel, MD, Charité Universitätsmedizin Berlin, Berlin, Germany, Renato Mantegazza, MD, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy, Djillali Annane, MD, Hôpital Raymond Poincaré, Garches, France, Masahisa Katsuno, MD, Nagoya University Graduate School of Medicine, Nagoya, Japan, Rasha Aguzzi, MD, Alexion, AstraZeneca Rare Disease, Boston, MA, USA, Ahmed Enayetallah, MD, PhD, Alexion, AstraZeneca Rare Disease, Boston, MA, USA, Chip Howard, MD, The University of North Carolina, Chapel Hill, NC, USA

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.
Objective:
To evaluate the efficacy and safety of ravulizumab in adults with generalized myasthenia gravis (gMG).
Methods:
In this multicenter, double-blind, phase 3 study (NCT03920293), adults with anti-acetylcholine receptor antibody-positive (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 induction on Day 1, then 3000–3600 mg every 8 weeks beginning on Day 15) or placebo for 26 weeks. Stable-dose acetylcholinesterase inhibitor and immunosuppressant 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 versus placebo (-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 (p<0.001 vs placebo). 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.