Abstract Details

Title 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

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) S15 - Autoimmune Neuromuscular Diseases: New Observations and Therapeutic Approaches (2:48 PM-3:00 PM)

Poster/Presentation
Number 010

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).

Objective

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

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.

Authors/Disclosures
Tuan H. Vu, MD (University of South Florida) PRESENTER	Dr. Vu has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Dianthus. Dr. Vu has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ImmunAbs. Dr. Vu has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ARGENX. Dr. Vu has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Vu has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. Dr. Vu has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amgen (Horizon). Dr. Vu has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Johnson & Johnson. Dr. Vu has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion. Dr. Vu has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for CSL Behring. Dr. Vu has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Argenx. The institution of Dr. Vu has received research support from CSL Behring. The institution of Dr. Vu has received research support from Alexion. The institution of Dr. Vu has received research support from RA Pharma/UCB. The institution of Dr. Vu has received research support from Mass Gen Hospital/Healy Platform Study. The institution of Dr. Vu has received research support from ARGENX. The institution of Dr. Vu has received research support from Horizon/Amgen. The institution of Dr. Vu has received research support from Woolsey Pharma. The institution of Dr. Vu has received research support from CSL Behring. The institution of Dr. Vu has received research support from Cartesian Therapeutics. The institution of Dr. Vu has received research support from Janssen/Johnson & Johnson. The institution of Dr. Vu has received research support from Immunovant. The institution of Dr. Vu has received research support from Regeneron. The institution of Dr. Vu has received research support from Dianthus. The institution of Dr. Vu has received research support from COUR.
Renato Mantegazza, MD	Dr. Mantegazza has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Mantegazza has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. Dr. Mantegazza has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for argenx. Dr. Mantegazza has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Mantegazza has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for SERB. The institution of Dr. Mantegazza has received research support from Alpine Immune Sciences, Inc.
Djillali Annane, MD	Dr. Annane has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. The institution of Dr. Annane has received research support from alexion.
Masahisa Katsuno (Nagoya University)	No disclosure on file
Andreas Meisel (Charité Universitätsmedizin Berlin)	No disclosure on file
Michael W. Nicolle, MD	Dr. Nicolle has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Nicolle has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Various legal firms.
Vera Bril, MD (Toronto General Hospital)	Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CSL. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alnylam. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Grifols. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Takeda. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Octapharma. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pfizer. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Powell Mansfield. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Akcea. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ionis. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Immunovant. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Momenta (now J&J). Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NovoNordisk. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Takeda. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunovant. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Bril has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Akcea. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alnylam. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for CSL. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx. The institution of Dr. Bril has received research support from UCB. The institution of Dr. Bril has received research support from Argenx. The institution of Dr. Bril has received research support from Momenta (now J&J). The institution of Dr. Bril has received research support from Immunovant. The institution of Dr. Bril has received research support from Alexion. The institution of Dr. Bril has received research support from Takeda. The institution of Dr. Bril has received research support from Grifols. The institution of Dr. Bril has received research support from CSL. The institution of Dr. Bril has received research support from Octapharma. The institution of Dr. Bril has received research support from Akcea. The institution of Dr. Bril has received research support from Ionis. The institution of Dr. Bril has received research support from Viela Bio (now Horizon). Dr. Bril has received intellectual property interests from a discovery or technology relating to health care.
Rasha Aguzzi (Alexion)	No disclosure on file
Glen Frick, MD, PhD	Dr. Frick has received personal compensation for serving as an employee of AstraZeneca/Alexion Rare Disease. Dr. Frick has stock in AstraZeneca/Alexion Rare Disease.
James F. Howard, Jr., MD, FAAN (The University of North Carolina, Dept of Neurology, CB 7025)	Dr. Howard has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for arenx . Dr. Howard has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Regeneron Pharmaceuticals. Dr. Howard has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion Pharmaceuticals. Dr. Howard has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ra Pharma (now UCB Biosciences). Dr. Howard has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon Therapeutics. Dr. Howard has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi US. Dr. Howard has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Howard has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Academic CME. Dr. Howard has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for PeerView CME. Dr. Howard has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Platform Q CME. Dr. Howard has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Zai Laboratories. Dr. Howard has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Medscape CME. Dr. Howard has stock in General Electric dividends. Dr. Howard has stock in Johnson & Johnson dividends. Dr. Howard has stock in Pfizer dividends. An immediate family member of Dr. Howard has stock in GlaxoSmithKline dividends. An immediate family member of Dr. Howard has stock in GE Healthcare dividends. The institution of Dr. Howard has received research support from Alexion Pharmaceuticals. The institution of Dr. Howard has received research support from argenx . The institution of Dr. Howard has received research support from UCB Biosciences. The institution of Dr. Howard has received research support from NIH. The institution of Dr. Howard has received research support from Centers for Disease Control/Research Triangle Institute. The institution of Dr. Howard has received research support from Duke University (DCRI). The institution of Dr. Howard has received research support from Cartestian Therapeutics. Dr. Howard has a non-compensated relationship as a Scientific Advisiory Board member, Committee member with Myasthenia Gravis Foundation of America that is relevant to AAN interests or activities. Dr. Howard has a non-compensated relationship as a Committee member with American Assoc Neuromuscular and Electrodiagnostic Medicine that is relevant to AAN interests or activities.