Efficacy and Safety of Autologous BCMA-directed mRNA CAR T-Cell Therapy in Generalized Myasthenia Gravis: Results from a Phase 2b Randomized Placebo-controlled Trial (S34.002)

Objective: Compare the effect of Descartes-08 versus placebo, as measured by the change in MG Composite (MGC) score from baseline to Month 3. Secondary: compare the effect of Descartes-08 versus placebo on MG-ADL and other measures of disease activity. Background: Descartes-08 is an autologous, BCMA-directed mRNA chimeric antigen receptor T-cell therapy administered in an outpatient setting and without chemotherapy. In a phase 1/2 study in generalized myasthenia gravis (MG), six weekly infusions of 52.5×10 6 CAR+ cells/kg per infusion led to deep and durable improvements in MG severity scales. Design/Methods: A phase 2b double-blind randomized controlled trial comparing six weekly infusions of Descartes-08 or placebo (NCT04146051) in adults with non-MuSK+ MG who required immunosuppressive therapy and had MG-ADL ≥6. After leukapheresis and manufacturing of autologous product, participants were randomized 1:1. Primary endpoint was the proportion of participants achieving ≥5-point improvement in MGC at Month 3. Results: Of 31 participants in the per protocol analysis, 18 were randomized to Descartes-08 and 13 to placebo, receiving median 6 doses (range 2–6). There were significantly more responders in the active arm in the overall population (67% versus 31%) and the AChR antibody-positive population (64% versus 20%). Mean change in MGC at Month 3 was −5.6 (Descrartes-08) versus −0.5 (placebo) in the AChR+ and −5.4 versus −2.7 in the overall population, with placebo response more pronounced in the triple-seronegative population. Mean change in MG-ADL at Month 3 was −3.4 versus −0.9 (AChR+) and −3.8 versus −1.7 (overall). There was no cytokine release syndrome observed. The most common side effects reported in the Descartes-08 group but not in the placebo group were all infusion-related reactions resolving within 48 hours. Conclusions: Outpatient Descartes-08 administration was associated with significant reduction in disease activity scores compared to placebo with no concerning safety signals. Efficacy of Descartes-08 will be tested in a Phase 3 trial. Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff. Disclosure: 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. Dr. Durmus has nothing to disclose. Author has nothing to discloseDr. Shroff has received personal compensation for serving as an employee of Alnylam. Dr. Shroff has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alnylam. The institution of Dr. Ragole has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion Pharmaceuticals. The institution of Dr. Ragole has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Ragole has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion Pharmaceuticals. The institution of Dr. Ragole has received research support from Alexion Pharmaceuticals. Author has nothing to discloseDr. Pasnoor has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Argenx BVBA. Dr. Pasnoor has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen Pharmaceutical. Dr. Pasnoor has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Immunovant. Dr. Pasnoor has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Pasnoor has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Annexon. Dr. Pasnoor has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for CSL Behring. Dr. Pasnoor has received personal compensation in the range of $500-$4,999 for serving as a Consultant for amgen. Dr. Small has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Karam has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alnylam. Dr. Karam has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ionis. Dr. Karam has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Karam has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Argenx. Dr. Karam has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Karam has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Neuroderm. Dr. Vullaganti has nothing to disclose. Dr. Peltier has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alnylam. Dr. Peltier has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for astrazeneca. Dr. Peltier has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for CSL Behring. Dr. Peltier has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Csl Behring. Dr. Peltier 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. Dr. Peltier has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for alnylam. Dr. Peltier has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for astrazeneca. Dr. Peltier has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Goldman Ismail. The institution of Dr. Peltier has received research support from NIH. The institution of Dr. Peltier has received research support from CSL Behring. Dr. Sahagian has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Argenx. Dr. Sahagian has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB Pharma. Dr. Sahagian has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. The institution of Dr. Sahagian 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. Sahagian has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB Pharma. The institution of Dr. Sahagian 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. Sahagian has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Argenx. The institution of Dr. Sahagian has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB Pharma. Dr. Sahagian has received intellectual property interests from a discovery or technology relating to health care. Dr. Feinberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acadia. Dr. Feinberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Catalyst. Dr. Feinberg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for eisai. Dr. Feinberg has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Argenx. Dr. Feinberg has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Abbvie. Dr. Feinberg has stock in Amarin. Dr. Barnett Tapia has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Argenx. Dr. Barnett Tapia has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Barnett Tapia has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB. Dr. Barnett Tapia 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. Barnett Tapia 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. Barnett Tapia has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen. Dr. Barnett Tapia has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. Dr. Barnett Tapia has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for argenx. The institution of Dr. Barnett Tapia has received research support from Department of defense. The institution of Dr. Barnett Tapia has received research support from Muscular dystrophy canada. The institution of Dr. Barnett Tapia has received research support from MgNet. The institution of Dr. Barnett Tapia has received research support from NIH. Dr. Barnett Tapia has received intellectual property interests from a discovery or technology relating to health care. Dr. Siddiqi has nothing to disclose. Dr. Jewell has received personal compensation for serving as an employee of Cartesian Therapeutics. Dr. Jewell has received personal compensation for serving as an employee of University of Maryland. Dr. Jewell has received personal compensation for serving as an employee of Baltimore VA Medical Center. Dr. Jewell has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Kerna Ventures. Dr. Jewell has received personal compensation in the range of $500,000-$999,999 for serving as an officer or member of the Board of Directors for Cartesian Therapeutics. Dr. Jewell has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Nature Publishing Group. Dr. Jewell has stock in Cartesian Therapeutics. Dr. Jewell has stock in Nodal Therapeutics. The institution of Dr. Jewell has received research support from NIH. The institution of Dr. Jewell has received research support from JDRF. The institution of Dr. Jewell has received research support from Baltimore VA Medical Center. Dr. Jewell has received intellectual property interests from a discovery or technology relating to health care. Dr. Jewell has received intellectual property interests from a discovery or technology relating to health care. Dr. Kurtoglu has received personal compensation for serving as an employee of Cartesian Therapeutics. Dr. Kurtoglu has stock in Cartesian Therapeutics. The institution of Dr. Kurtoglu has received research support from National Institute of Health. Hafsa Kamboh has stock in Cartesian Therapeutics, Inc. Dr. Miljkovic has received personal compensation for serving as an employee of Cartesian Therapeutics. Dr. Miljkovic has received personal compensation in the range of $100,000-$499,999 for serving as an officer or member of the Board of Directors for Cartesian Therapeutics. Dr. Miljkovic has stock in Cartesian Therapeutics. Dr. Mozaffar has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion Pharmaceuticals. Dr. Mozaffar has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Argenx. Dr. Mozaffar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Mozaffar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Amicus. Dr. Mozaffar has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Grifols. Dr. Mozaffar has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Astellas Gene Therapy. Dr. Mozaffar has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bayer. Dr. Mozaffar has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta. Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Applied Therapeutics. The institution of Dr. Mozaffar has received research support from NIH. The institution of Dr. Mozaffar has received research support from Muscular Dystrophy Association. The institution of Dr. Mozaffar has received research support from Sanofi. The institution of Dr. Mozaffar has received research support from Argenx. The institution of Dr. Mozaffar has received research support from Amicus Therapeutics. The institution of Dr. Mozaffar has received research support from Astellas Gene Therpay. The institution of Dr. Mozaffar has received research support from Cartesian. The institution of Dr. Mozaffar has received research support from Cabaletta. Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving as a Study Section Member with NIH. 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 $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AMGEN (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 $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven Ltd. 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 CorEvitas. 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 Merck EMD Serono. 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 received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for MJH LifeSci. 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. Dr. Howard has stock in Viatris. 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. The institution of Dr. Howard has received research support from NMD Pharma. The institution of Dr. Howard has received research support from Ad Scientiam. 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.