Long-term Efficacy and Safety of Ravulizumab, a Long-acting Terminal Complement Inhibitor, in Adults with Anti-acetylcholine Receptor Antibody-positive Generalized Myasthenia Gravis: Final Results from the Phase 3 CHAMPION MG Open-label Extension
Tuan Vu1, Renato Mantegazza2, Djillali Annane3, Masahisa Katsuno4, Andreas Meisel5, Michael Nicolle6, Vera Bril7, Rasha Aguzzi8, Glen Frick8, James Howard9
1University of South Florida Morsani College of Medicine, 2Fondazione IRCCS Istituto Neurologico Carlo Besta, 3Hôpital Raymond Poincaré, 4Nagoya University Graduate School of Medicine, 5Charité Universitätsmedizin Berlin, 6London Health Sciences Centre, 7University of Toronto, 8Alexion, AstraZeneca Rare Disease, 9The University of North Carolina
Objective:
To evaluate the long-term efficacy and safety of ravulizumab in adults with anti-acetylcholine receptor antibody-positive (AChRAb+) generalized myasthenia gravis (gMG).
Background:
The 26-week, double-blind, randomized, placebo-controlled period (RCP) of the CHAMPION MG study demonstrated the efficacy and favorable safety profile of ravulizumab in adults with AChRAb+ gMG. Participants who completed the RCP could receive ravulizumab in the open-label extension (OLE; NCT03920293).
Design/Methods:
In the OLE, patients could receive intravenous ravulizumab (blind induction or bridging dose at Week 26 [OLE start] for those previously receiving placebo or ravulizumab, respectively, then 3000–3600 mg according to body weight at Week 28 and every 8 weeks thereafter) for up to 4 years at database lock. Assessments included Myasthenia Gravis–Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) total scores, and safety evaluations.
Results:
The final analysis included data from 161 patients (78 received ravulizumab, 83 received placebo in the RCP) who entered the OLE and received ravulizumab for up to 164 weeks. Mean duration of ravulizumab treatment was ~2 years. Improvements in MG-ADL total score seen in ravulizumab-treated patients in the RCP were maintained: least-squares mean change from RCP baseline at Week 164 was -4.0 (95% confidence interval [CI] -5.3, -2.8; p<0.0001). Patients who switched from placebo in the RCP to ravulizumab in the OLE showed rapid improvements in MG-ADL score, which were maintained through 138 weeks (least-squares mean change from OLE baseline at Week 164: -2.1 [95% CI -3.3, -0.9]; p<0.0005). QMG total score improvements were also maintained in patients continuing ravulizumab in the OLE and scores improved from OLE baseline in patients switching from placebo to ravulizumab. Ravulizumab was well tolerated; no meningococcal infections were reported.
Conclusions:
Ravulizumab, administered every 8 weeks, demonstrated clinically meaningful sustained improvements in MG symptoms and was well tolerated for up to 164 weeks in adults with AChRAb+ gMG.