Abstract Details

Title RAISE-XT: An interim analysis of safety and efficacy in an open-label extension study of zilucoplan in patients with myasthenia gravis

Presentations P1 - Poster Session 1

Background Long-term data from RAISE-XT (NCT04225871), a Phase 3, multicenter, open-label extension study, will enhance our understanding of the safety and efficacy of the C5 inhibitor zilucoplan in patients with gMG.

Objective Evaluate the safety and efficacy of zilucoplan in patients with generalized myasthenia gravis (gMG).

Design/Methods Adults (≥18, <75 years) with gMG who completed a qualifying zilucoplan study (NCT03315130/NCT04115293) self-administered daily subcutaneous injections of zilucoplan 0.3 mg/kg. Primary outcome was incidence of treatment-emergent adverse events (TEAEs). Secondary outcomes included change from qualifying study baseline to Extension Week 12 (Week E12) in Myasthenia Gravis Activities of Daily Living (MG-ADL) score, responder rates for MG-ADL and Quantitative Myasthenia Gravis (QMG; reduction of ≥3 points and ≥5 points without rescue therapy, respectively), and minimal symptom expression (MSE; MG-ADL 0/1).

Results Among 199 patients enrolled in RAISE-XT, 104 continued zilucoplan from their parent study (zilucoplan group) and 95 switched to zilucoplan from placebo (placebo-switch group). Median exposure at data cut-off was 253 days (range 29–1434). TEAEs occurred in 169 (84.9%) patients; 46 (23.1%) patients experienced a serious TEAE. At Week E12, LS mean changes in MG-ADL score for the zilucoplan and placebo-switch groups (after 24 and 12 weeks of zilucoplan, respectively) were −6.30 (95% CI: −7.44, −5.15) and −6.32 (95% CI: −8.00, −4.65). MG-ADL responder rates improved from extension study baseline through Week E12 (zilucoplan: 75.0% to 80.3% of patients; placebo-switch: 52.2% to 79.7%); a similar effect was observed on QMG responder rates. MSE responder rate increased through Week E12 (zilucoplan: 19.6% to 26.8% of patients; placebo-switch: 7.8% to 29.0%).

Conclusions In this interim analysis of RAISE-XT, zilucoplan demonstrated a favorable long-term safety profile and sustained efficacy. Responder rates improved from extension study baseline in both the zilucoplan and placebo-switch groups. Funding: UCB Pharma.

Authors/Disclosures
Miriam L. Freimer, MD, FAAN (The Ohio State University) PRESENTER	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.
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 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.
Henry J. Kaminski, MD, FAAN (George Washington University)	The institution of Dr. Kaminski has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Kaminski has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Kaminski has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cabaletta Bio. Dr. Kaminski has stock in ARC Biotechnology. The institution of Dr. Kaminski has received research support from National Institutes of Health. Dr. Kaminski has received publishing royalties from a publication relating to health care.
Angela L. Genge, MD (Mcgill University)	Dr. Genge has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for AL-S Pharma. Dr. Genge has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Genge has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cytokinetics. Dr. Genge has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Amylyx. Dr. Genge has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Quralis. Dr. Genge has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Genge has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MTPA. Dr. Genge has received personal compensation in the range of $0-$499 for serving as a Consultant for WAVE.
Tuan Hoang Vu, MD (University of South Florida)	Dr. Vu has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BPL. Dr. Vu has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Takeda. 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 $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. 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 AbbVie. Dr. Vu has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Argenx. Dr. Vu has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for MedScape. 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 Mitsubishi Tanaka. 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 Amylyx Pharma. The institution of Dr. Vu has received research support from ARGENX. The institution of Dr. Vu has received research support from Alector. The institution of Dr. Vu has received research support from Annexon. The institution of Dr. Vu has received research support from Apellis. The institution of Dr. Vu has received research support from Cytokinetics. The institution of Dr. Vu has received research support from Sanofi. The institution of Dr. Vu has received research support from Horizon. 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/Momenta.
Maria Isabel Leite, MD (Nuffield Department of Clinical Neurosciences - University of Oxford)	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.
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.
Petra W. Duda, MD, PhD (UCB Pharma)	Dr. Duda has received personal compensation for serving as an employee of UCB. Dr. Duda has stock in UCB.
Babak Boroojerdi, MD (UCB Biosciences GmbH)	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.
Kimiaki Utsugisawa, MD,PhD (Hanamaki General Hospital)	Dr. Utsugisawa 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. Utsugisawa 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 pharma. Dr. Utsugisawa has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen pharma. Dr. Utsugisawa has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Viela Bio. Dr. Utsugisawa has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Chugai. Dr. Utsugisawa has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Mitsubisi Tanabe pharma. Dr. Utsugisawa has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Utsugisawa has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for argenx. Dr. Utsugisawa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion phama. Dr. Utsugisawa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Japan Blood Products Organization. Dr. Utsugisawa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB.
Yessar M. Hussain, MD (Austin Neuromuscular Center)	Dr. Hussain has nothing to disclose.
Mark Louis Vanderkelen, MD (UCB Pharma)	Dr. Vanderkelen has received personal compensation for serving as an employee of UCB Pharma. Dr. Vanderkelen has stock in UCB Pharma.
Romana Lowcock, Other	The institution of Mrs. Lowcock has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for UCB.