Twelve-Month Follow-Up of Patients With Generalized Myasthenia Gravis Receiving BCMA-Directed mRNA Cell Therapy

We report the 12-month follow-up results of a phase 2 clinical of Descartes-08 ([NCT04146051][1]), BCMA-directed RNA chimeric antigen receptor T-cell (rCAR-T) therapy for myasthenia gravis (MG) given as an outpatient treatment without lymphodepletion. In the Phase 2a part of the study, all 7 participants who received six weekly infusions of Descartes-08 exhibited clinically meaningful improvement in common MG severity scales (MG Composite, MG Activities of Daily Living, Quantitative MG scores, and Quality of Life 15-revised) at Month 3. At Month 9 follow-up, all participants continued to experience marked clinical improvements. Five out of seven participants maintained clinical improvement at Month 12. Of the two participants who experienced loss of clinical effect at Month 12 and were eligible for retreatment, one was retreated and had rapid improvement in clinical scores with minimal symptom expression which was ongoing at Month 6 of follow-up. All three participants with detectable anti-acetylcholine receptor (AChR) antibody levels at baseline experienced autoantibody reductions by Month 6, which deepened further by Month 9, and were maintained at Month 12. These data support continued development of Descartes-08 in myasthenia gravis and other autoantibody-associated autoimmune disorders. ### Competing Interest Statement G Sahagian has received research support from Cartesian Therapeutic, Inc., Immunovant, and argenx paid to his institution; consulting fees from UCB pharma and Immunovant; honoraria from argenx and Alexion, and travel support from argenx and Immunovant; he also has unpaid positions at MGFCA and AANEM. M Feinberg has received honoraria as a consultant or advisory board member from argenx. CM Jewell has an equity position in Barinthus Biotherapeutics. CM Jewell, M Kurtoglu, and MD Miljkovic are employees of and have ownership interest in Cartesian Therapeutics, Inc. CM Jewell is appointed as an employee of the University of Maryland and VA Maryland Health Care System. The views in this paper do not reflect the views of the state of Maryland or the US Government. MD Miljkovic is appointed as an employee of the University of Maryland Baltimore County. The views in this paper do not reflect the views of the state of Maryland. T Vu is the USF Site Principal Investigator for MG clinical trials sponsored by Alexion/AstraZeneca, argenx, Ra/UCB, Horizon/Viela Bio, Janssen/Momenta, Immunovant, Regeneron, Dianthus, and Cartesian Therapeutics, and receives speaking and/or consulting honoraria relating to MG from Alexion, argenx, and UCB. T Mozaffar has received research support (paid to his institution) from Alexion Pharmaceuticals, Inc, Amicus, Annji, argenx, Astellas Gene Therapy, Cartesian Therapeutics, ML Bio, Sanofi, Spark Therapeutics, UCB and Valerion; consulting fees from Alexion Pharmaceuticals, Inc, Amicus, Annji, argenx, Audentes/Astellas Gene Therapy, Horizon Therapeutics, Maze Therapeutics, Momenta, Sanofi and UCB; support for attending meetings and/or travel from Sanofi; participation on a DSMB or an advisory board from Srepta, Applied Therapeutics, and the National Institutes of Health. JF Howard, Jr. has received research support (paid to his institution) from Alexion AstraZeneca Rare Disease, argenx, Cartesian Therapeutics, the Centers for Disease Control and Prevention, Myasthenia Gravis Foundation of America, Muscular Dystrophy Association, National Institutes of Health (including the National Institute of Neurological Disorders and Stroke and the National Institute of Arthritis and Musculoskeletal and Skin Diseases), Patient-Centered Outcomes Research Institute, Ra Pharmaceuticals Inc (now UCB), and Takeda Pharmaceuticals; honoraria from Alexion AstraZeneca Rare Disease, argenx, Biologix Pharma, Immunovant, Inc, Merck EMB Serono, NMD Pharma, Novartis Pharma, Ra Pharmaceuticals Inc (now UCB), Regeneron Pharmaceuticals Inc, Sanofi US, Viela Bio/ Horizon Therapeutics plc, Inc (now Amgen) and Zai Labs; he has also received nonfinancial support from Alexion Pharmaceuticals, Inc, argenx BV, Ra Pharmaceuticals Inc (now UCB), Toleranzia AB and Zai Labs. All other authors declare no competing interests. ### Clinical Trial NCT04146051 ### Funding Statement Research reported in this publication was supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under Awards Number R25NS088248 and NS115426-01A1. Study was sponsored by Cartesian Therapeutics, Inc. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: A central Institutional Review Board (Western IRB) gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Access to anonymised, individual, and trial-level data (analysis datasets) will be provided by request from qualified researchers performing independent, rigorous research, after review and approval of a research proposal and statistical analysis plan and execution of a data sharing agreement. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04146051&atom=%2Fmedrxiv%2Fearly%2F2024%2F01%2F04%2F2024.01.03.24300770.atom