Subgroup outcomes from RAISE: A randomized, Phase 3 trial of zilucoplan in generalized myasthenia gravis (P1-5.006)

Objective:

To evaluate the efficacy of zilucoplan in patients with acetylcholine receptor autoantibody positive (AChR Ab+) generalized myasthenia gravis (gMG), stratified to specific disease characteristics.

Background:

RAISE (NCT04115293) was a Phase 3, multicenter, double-blind, placebo-controlled study of zilucoplan, a macrocyclic peptide inhibitor of complement C5, that resulted in statistically significant and clinically meaningful improvement in MG-related efficacy endpoints (primary endpoint: MG-ADL score; LS mean change from baseline [CFB] in zilucoplan: −4.39 vs placebo −2.30, difference −2.09, p<0.001), in patients with AChR Ab+ gMG.

Design/Methods:

Adult participants (MGFA Disease Class II–IV gMG, AChR Ab+, MG-ADL score ≥6, QMG score ≥12) were randomized 1:1 to daily subcutaneous doses of zilucoplan 0.3 mg/kg or matched placebo for 12 weeks. The primary efficacy endpoint was CFB at Week 12 in MG-ADL score. Subgroups were pre-specified according to the following baseline disease characteristics: MG-ADL ≤9 or ≥10, QMG ≤17 or ≥18, and disease duration <5 or ≥5 years.

Results:

Overall, 174 participants were randomized to zilucoplan (n=86) or placebo (n=88). At Week 12, the mean CFB in MG-ADL for zilucoplan vs placebo was consistently improved in each subgroup: baseline MG-ADL: ≤9: −3.88 vs −2.48 and ≥10: −5.24 vs −3.06; baseline QMG: ≤17: −4.19 vs −2.81 and ≥18: −5.11 vs −2.88; and duration of disease: <5 years: −3.92 vs −3.04 and ≥5 years: −5.38 vs −2.62. Mean CFB at Week 12 for QMG and MGC were also consistently improved with zilucoplan vs placebo, across all subgroups. Zilucoplan showed a favorable safety profile and was well-tolerated.

Conclusions:

Daily subcutaneous zilucoplan demonstrated consistent improvements in MG-specific efficacy outcomes irrespective of disease severity or duration. Funding: UCB Pharma. Disclosure: Dr. Weiss has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB-RA. Dr. Weiss has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Weiss has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Argenx. Dr. Weiss has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Alexion. Dr. Weiss has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amylyx. Dr. Weiss has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Weiss has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Soleo. Dr. Bresch has nothing to disclose. Dr. Freimer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Argenx. Dr. Freimer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB Pharma. Dr. Freimer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Freimer 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. Freimer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ra. Dr. Freimer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for immunovant. The institution of Dr. Freimer has received research support from Alnylum. The institution of Dr. Freimer has received research support from UCB. The institution of Dr. Freimer has received research support from NIH. The institution of Dr. Freimer has received research support from Janssen. Dr. Freimer has received research support from Avidity. Dr. Freimer has received research support from Fulcrum. Dr. Hewamadduma has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Hewamadduma has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ARENX. Dr. Hewamadduma has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BIOGEN. Dr. Hewamadduma has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ROCHE. The institution of Dr. Hewamadduma has received research support from Neurocare . The institution of Dr. Hewamadduma has received research support from Sheffield Charitable Trust. Dr. Hewamadduma has received personal compensation in the range of $5,000-$9,999 for serving as a Adult Expert with National Health Service England (NHSE). Raul Juntas-Morales has nothing to disclose. The institution of Dr. Leite has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. The institution of Dr. Leite has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Viela/Horizon. The institution of Dr. Leite has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx. The institution of Dr. Leite has received research support from Non-Profit Organization - Myaware. The institution of Dr. Leite has received research support from UCB - Ra Pharma. Dr. Maniaol has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Maniaol has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. The institution of Dr. Maniaol has received research support from ALS patient organization Alltid litt sterkere. Masayuki Masuda has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Alexion pharma, Argenix pharma, Aasahi kasei pharma. Dr. Sivakumar has nothing to disclose. Dr. Zajda has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Signant Health. Dr. Boroojerdi has received personal compensation for serving as an employee of UCB Biosciences. Dr. Boroojerdi has received stock or an ownership interest from UCb Biosciences. Dr. Duda has received personal compensation for serving as an employee of UCB. Dr. Duda has stock in UCB. Mrs. De La Borderie has received personal compensation for serving as an employee of UCB Pharma. Mrs. De La Borderie has stock in UCB Pharma. 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 BVBA. 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 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 $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunivant. 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 Viela Bio (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 $10,000-$49,999 for serving on a Speakers Bureau for Academic 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. The institution of Dr. Howard has received research support from Alexion Pharmaceuticals. The institution of Dr. Howard has received research support from argenx BVBA. The institution of Dr. Howard has received research support from Ra Pharma (now 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 Millenium Pharmaceuticals. 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.