Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2026 Mar;32(3):1131-1141.
doi: 10.1038/s41591-025-04171-y. Epub 2026 Jan 9.

BCMA-directed mRNA CAR T cell therapy for myasthenia gravis: a randomized, double-blind, placebo-controlled phase 2b trial

Tuan Vu  1 , Hacer Durmus  2 , Michael Rivner  3 , Sheetal Shroff  4 , Thomas Ragole  5 , Bennett Myers  6 , Mamatha Pasnoor  7 , George Small  8 , Chafic Karam  9 , Mithila Vullaganti  10 , Amanda Peltier  11 , Gregory Sahagian  12 , Marc H Feinberg  13 , Adam Slanksy  14 , Carolina Barnett-Tapia  15 , Zaeem Siddiqi  16 , Kelly Gwathmey  17 , Michael A Badruddoja  18 , Hafsa Kamboh  19 , Rachel N Ruggerie  19 , Renee R Fedak  19 , C Andrew Stewart  19 , Metin Kurtoglu  19 , Murat Kalayoglu  19 , Michael Singer  19 , Christopher M Jewell  19 , Milos D Miljkovic  19 , Mazen Dimachkie  7 , Tahseen Mozaffar  20 , James F Howard Jr  21 ; MG-001 Study Team
Affiliations
Clinical Trial

BCMA-directed mRNA CAR T cell therapy for myasthenia gravis: a randomized, double-blind, placebo-controlled phase 2b trial

Tuan Vu et al. Nat Med. 2026 Mar.

Abstract

Myasthenia gravis (MG) is driven by the secretion of autoantibodies from pathogenic B cell maturation antigen (BCMA)-expressing plasma cells. In this phase 2b randomized, controlled, double-blind trial, we evaluated Descartes-08, an autologous BCMA-directed mRNA chimeric antigen receptor T cell therapy, in patients with generalized MG (gMG). Patients (n = 26) were randomly allocated to receive once-weekly intravenous infusions of Descartes-08 (n = 15) or placebo (n = 11) over 6 weeks. The primary endpoint was a ≥5-point improvement in the MG Composite (MGC) score at month 3. Secondary endpoints included the mean change from baseline in MGC, MG Activities of Daily Living (MG-ADL) and Quantitative MG (QMG) scores by month 12. At month 3, the proportion of patients achieving a ≥5-point improvement in the MGC score was significantly higher for those treated with Descartes-08 compared to placebo in the overall population (66.7% (n = 10/15) versus 27.3% (n = 3/11), P = 0.0472) and in a subpopulation of those positive for autoantibodies to the acetylcholine receptor (63.6% (n = 7/11) versus 12.5% (n = 1/8), P = 0.0258). For patients treated with Descartes-08, the changes from baseline in mean MGC, MG-ADL and QMG scores at month 4 were -7.1, -5.5 and -4.8, respectively, with 83.0% of patients achieving a sustained and clinically meaningful response at month 12. Notably, 33.0% of patients achieved minimum symptom expression (MSE) (MG-ADL score ≤1) by month 6, which was sustained through month 12. Among biologic-naive patients, 55.60% achieved MSE by month 6, which was maintained through month 12 without additional treatment. Descartes-08 was generally safe and well tolerated. Infusion-related reactions were the most common adverse events reported (Descartes-08, 80.0% (n = 16/20); placebo, 56.3% (n = 9/16)). In summary, a single course of six once-weekly infusions of Descartes-08 was well tolerated and resulted in sustained clinically meaningful responses among patients with gMG. ClinicalTrials.gov identifier: NCT04146051 .

PubMed Disclaimer

Conflict of interest statement

Competing interests: H.K., R.N.R., R.R.F., C.A.S., M. Kurtoglu, M. Kalayoglu, M.S., C.M.J. and M.D.M. are employees of and/or hold equity in Cartesian Therapeutics. C.M.J. is appointed as a professor at the University of Maryland and as a Research Health Scientist at the VA Maryland Health Care System. The views in this paper do not reflect the views of the state of Maryland or the US government. C.M.J. is a founder of Nodal Therapeutics and Patch Bio and holds equity positions with Nodal Therapeutics, Patch Bio, Aletira Therapeutics and Barinthus Biotherapeutics. C.B.-T. has served as a member of the advisory board for argenx, Alexion, UCB, Janssen and NMD Pharma. She has been a consultant for argenx, Janssen, Novartis and UCB. She has received research support from the US Department of Defense, Muscular Dystrophy Canada and MGNet. She is the primary developer of the Myasthenia Gravis Impairment Index (MGII) and may receive royalties. T.V. is a site principal investigator at the University of South Florida for myasthenia gravis clinical trials sponsored by Alexion/AstraZeneca, argenx, Amgen, Cartesians, COUR, Dianthus, EMD Serono, Johnson & Johnson, Immunovant, NMD Pharma, Regeneron and UCB. T.V. received speaking and/or consulting honoraria related to myasthenia gravis from Alexion, Amgen, argenx, Dianthus and Johnson & Johnson. T.M. has received research funding from the Muscular Dystrophy Association and the National Institutes for Health (R01AR074457, UM1TR004927, R21AR082649, UO1NS139215 and f T32AR083870). T.M. has received research funding from the following sponsors: Alexion, Amicus, AnnJi, Argenx, Aro Bio, Ask Bio, Audentes (now Astellas Gene Therapy), Cabaletta, Cartesian Therapeutics, Fate Therapeutics, ML-Bio, Momenta, NKarta, Ra Pharmaceuticals, Sanofi, Spark Therapeutics and Valerion. T.M. has served as a consultant for Alexion, Amicus, AnnJi, Argenx, Aro Bio, Arvinas, Ask Bio, Astellas Gene Therapeutics, AvroBio, BioCryst, Cabaletta, Creyon, Dyne, Fate Therapeutics, Horizon Therapeutics, Immunovant, Maze Therapeutics, Merck, Poseida, Regeneron, Shionogi, Momenta (now Janssen), Sanofi, UCB and Variant Bio. T.M. serves on the medical advisory board for the Myositis Association and the Neuromuscular Disease Foundation. He serves on the data safety monitoring board for Acceleron, Applied Therapeutics (Chair), Avidity, Sarepta, Sirolimus in IBM trial (Chair) and the NI. J.F.H. discloses research funding (paid to his institution) from Ad Scientiam, Alexion AstraZeneca Rare Disease, argenx, Cartesian Therapeutics, Centers for Disease Control and Prevention, Merck EMD Serono, MGFA, Muscular Dystrophy Association, NIH, NMD Pharma and UCB Bioscience; honoraria/consulting fees from AcademicCME, Alexion AstraZeneca Rare Disease, Amgen, argenx, Biohaven Ltd, Cartesian Therapeutics, CheckRare CME, CoreEvitas, Curie.bio, H. Lundbeck A/S, Japan Tobacco Company, Merck EMB Serono, NMD Pharma, Novartis Pharma, PeerView CME, Physicians′ Education Resource (PER) CME, PlatformQ CME, Regeneron Pharmaceuticals, Seismic Therapeutics, TG Therapeutics, Toleranzia AB and UCB Pharma. H.D. has served as a speaker and consultant for Alexion/AstraZeneca and UCB. K.G. received speaking honoraria (remotely) for Alexion /AstraZebeca and Argenx, consulting honoraria for Alexion/AstraZeneca, Amgen, Novartis and UCB. She also served as a DSMB member for Cabaletta and Cour. C.K. served as a consultant and/or on an advisory board for Acceleron, Alpine, Alexion/AstraZeneca, Alnylam, Amgen, Amicus, Annexon, Applied Therapeutics, Argenx, Catalyst, Corino, Biogen, CSL Behring, Genentech, Immunovant, Intellia, Ionis, J&J, Medison, Neuroderm, Novo Nordisk, Nuvig, Octapharma, Pfizer, Sanofi, UCB, Takeda, Vertex and Zai Lab. S.S. served as a speaker and/or consultant for UCB, Argenx and Astra Zeneca. G. Sahagian has received funding as an Investigator for clinical trials sponsored by Argenx, Sanofi, Lilly, Biogen, Cartesian, Immunovant, NMD Pharma, Regeneron and UCB. He received speaking and/or consulting honoraria from Alexion/AstraZeneca, Amgen, Argenx, Biogen, Cartesian and Immunovant. M.D received consultancy fees, payment or honoraria for lectures, presentations, manuscript writing or educational events, and participated on a Data Safety Monitoring Board or Advisory Board for Abcuro, Amicus, Annexon, ArgenX, Astellas, Cabaletta Bio, Catalyst, Covance/Labcorp/Fortrea, CSL-Behring, Creyon Bio, Inc., Dianthus, EMD Serono/Merck, Horizon, Ig Society, Inc, Janssen, Medlink, Nuvig, Octapharma, Sanofi Genzyme, Shire Takeda and TACT/Treat NMD and Vertex. M.M.D. has received grants or from Abcuro, Alexion/ AstraZeneca, Alnylam Pharmaceuticals, Amicus, ArgenX, Biosensics, Bristol-Myers Squibb, Cabaletta Bio, Catalyst, CSL-Behring, EMD Serono, FDA/OOPD, GlaxoSmithKline, Genentech, Grifols, Horizon Immnunovant, Mitsubishi Tanabe Pharma, MDA, NIH, Nkarta, Novartis, Octapharma, Orphazyme, Priovant, Ra Pharma/UCB Biopharma, Sanofi Genzyme, Sarepta Therapeutics, Shire Takeda, Spark Therapeutics and The Myositis Association. M.D. received royalty for manuscript writing from Wolters Kluwer Health/UpToDate and from Elsevier and for discovery relating to health care from Zevra Therapeutics. Z.S. has served as member of the advisory boards or Site Principal Investigator for clinical trials sponsored by Argenx, Alexion/AstraZeneca, UCB, Janssen, CSL Behring, Takeda, Regeneron, Immunovant, Novartis and Pfizer. The other authors declare no competing interests.

Figures

Fig. 1
Fig. 1. CONSORT diagram for the MG-001 part 3 study.
The numbers of participants who were assessed, enrolled, randomized, treated and included in analyses are shown.
Fig. 2
Fig. 2. Change from baseline in disease severity scores over the study period.
Mean (95% CI) change from baseline over 3 months for placebo and over 12 months for Descartes-08 in MG-ADL (a), QMG (b), MGC (c) and MG-QoL-15r (d) scores. Direction of improvement is indicated by decreasing scores. Horizontal dotted line represents the threshold for a clinically meaningful decrease. D, day; M, month.
Fig. 3
Fig. 3. Minimum point improvement in disease severity scores in patients with AChR antibody-positive MG.
Minimum improvement at month 3 in mean MG-ADL (a) and MGC (b) scores in patients with AChR antibody-positive MG treated with either Descartes-08 or placebo. Values represent the percentage of participants in each treatment group achieving minimum point improvement.
Extended Data Fig. 1
Extended Data Fig. 1. Change in MG-ADL score for AChR autoantibody-positive and -negative participants.
Mean (95% CI) change from baseline in MG-ADL score over 3 months for placebo and over 12 months for Descartes-08 in AChR autoantibody-positive and -negative participants. Orange dashed line represents the threshold for a clinically meaningful reduction in MG-ADL score. AChR, acetylcholine receptor; CI, confidence interval; MG-ADL, Myasthenia Gravis Activities of Daily Living.
Extended Data Fig. 2
Extended Data Fig. 2. Change in MG-ADL score for biologic-naïve and biologic-exposed participants.
Mean (95% CI) change from baseline in MG-ADL score over 3 months for placebo and over 12 months for Descartes-08 in biologic naïve and biologic-exposed participants. Biologic-exposed participants were non-responders to prior FcRn or complement inhibitor treatment. Orange dashed line represents the threshold for a clinically meaningful reduction in MG-ADL score. CI, confidence interval; FcRn, fragment crystallizable (neonatal); MG-ADL, Myasthenia Gravis Activities of Daily Living.
See this image and copyright information in PMC

References

    1. Lazaridis, K. & Tzartos, S. J. Myasthenia gravis: autoantibody specificities and their role in MG management. Front. Neurol.11, 596981 (2020). - DOI - PMC - PubMed
    1. Dresser, L., Wlodarski, R., Rezania, K. & Soliven, B. Myasthenia gravis: epidemiology, pathophysiology and clinical manifestations. J. Clin. Med.10, 2235 (2021). - DOI - PMC - PubMed
    1. Koneczny, I. & Herbst, R. Myasthenia gravis: pathogenic effects of autoantibodies on neuromuscular architecture. Cells8, 671 (2019). - DOI - PMC - PubMed
    1. McCallion, J. et al. Systematic review of the patient burden of generalised myasthenia gravis in Europe, the Middle East, and Africa. BMC Neurol.24, 61 (2024). - DOI - PMC - PubMed
    1. Gerischer, L., Doksani, P., Hoffmann, S. & Meisel, A. New and emerging biological therapies for myasthenia gravis: a focussed review for clinical decision-making. BioDrugs39, 185–213 (2025). - DOI - PMC - PubMed

Publication types

MeSH terms

Associated data