Poster 8
Efficacy and safety of autologous B‑cell maturation antigen-directed messenger RNA CAR T‑cell therapy, Descartes-08, in generalized myasthenia gravis: 12-month follow-up of a phase 2b randomized placebo-controlled trial Efficacy and safety of autologous B‑cell maturation antigen-directed messenger RNA CAR T‑cell therapy...
2025 American Association of Neuromuscular and Electrodiagnostic Medicine, October 31, 2025, San Francisco, CA, USA
Affiliations
T. Vu
University of South Florida, Tampa, FL, USA.
H.D. Tekce
Istanbul University, Istanbul, Turkey.
M. Rivner
Augusta University, Augusta, GA, USA.
S. Shroff
Houston Methodist Hospital, Houston, TX, USA.
T. Ragole
University of Colorado, Aurora, CO, USA.
B. Myers
Dent Neurologic Institute, Amherst, NY, USA.
M. Pasnoor
University of Kansas Medical Center, Kansas City, KS, USA.
G. Small
Allegheny General Hospital, Pittsburgh, PA, USA.
K. Gwathmey
Virginia Commonwealth University, Richmond, VA, USA.
C. Karam
University of Pennsylvania, Philadelphia, PA, USA.
M. Vullaganti
Tufts University, Boston, MA, USA.
A. Peltier
Vanderbilt University, Nashville, TN, USA.
G. Sahagian
Profound Research, San Diego, CA, USA.
M.H. Feinberg
SFM Research, Boca Raton, FL, USA.
A. Slansky
Neurology Associates, P.A., Maitland, FL, USA.
C. Barnett-Tapia
Toronto General Hospital, Toronto, Canada.
M. Badruddoja
Center for Neurosciences, Tucson, AZ, USA.
Z. Siddiqi
University of Alberta, Edmonton, Canada.
H. Kamboh
M. Kurtoglu
C.M. Jewell
M.D. Miljković
Cartesian Therapeutics, Frederick, MD, USA.
T. Mozaffar
University of California, Irvine, CA, USA.
J.F. Howard
University of North Carolina, Chapel Hill, NC, USA.
University of South Florida, Tampa, FL, USA.
H.D. Tekce
Istanbul University, Istanbul, Turkey.
M. Rivner
Augusta University, Augusta, GA, USA.
S. Shroff
Houston Methodist Hospital, Houston, TX, USA.
T. Ragole
University of Colorado, Aurora, CO, USA.
B. Myers
Dent Neurologic Institute, Amherst, NY, USA.
M. Pasnoor
University of Kansas Medical Center, Kansas City, KS, USA.
G. Small
Allegheny General Hospital, Pittsburgh, PA, USA.
K. Gwathmey
Virginia Commonwealth University, Richmond, VA, USA.
C. Karam
University of Pennsylvania, Philadelphia, PA, USA.
M. Vullaganti
Tufts University, Boston, MA, USA.
A. Peltier
Vanderbilt University, Nashville, TN, USA.
G. Sahagian
Profound Research, San Diego, CA, USA.
M.H. Feinberg
SFM Research, Boca Raton, FL, USA.
A. Slansky
Neurology Associates, P.A., Maitland, FL, USA.
C. Barnett-Tapia
Toronto General Hospital, Toronto, Canada.
M. Badruddoja
Center for Neurosciences, Tucson, AZ, USA.
Z. Siddiqi
University of Alberta, Edmonton, Canada.
H. Kamboh
M. Kurtoglu
C.M. Jewell
M.D. Miljković
Cartesian Therapeutics, Frederick, MD, USA.
T. Mozaffar
University of California, Irvine, CA, USA.
J.F. Howard
University of North Carolina, Chapel Hill, NC, USA.
Acknowledgments & disclosures
Acknowledgments
This study was funded by Cartesian Therapeutics. Medical writing and editorial support was provided by Laura Graham, PhD, and Nick Gibbs of Ogilvy Health and Eva Rybak, PharmD, of Cartesian Therapeutics.
Author disclosures
This study was funded by Cartesian Therapeutics. HK, MK, CMJ, and MDM are employed by, and may hold stocks in, Cartesian Therapeutics. TV: associations with and fees received from Alexion/AstraZeneca Rare Disease, Amgen, argenx, Cartesian Therapeutics, COUR, CSL Behring, Dianthus Therapeutics, EMD Serono, ImmunAbs, Immunovant, Johnson & Johnson, NMD Pharma, Regeneron, and UCB. HDT: fees from Alexion and UCB. MR: fees and/or grant support from Alexion, Amylyx, Apellis Pharma, argenx, Biohaven Pharmaceuticals, Inc., Cartesian Therapeutics, Catalyst Pharmaceuticals, Cytokinetics, Inc., Grifols, Healey Center, Janssen Research and Development, Mallinckrodt ARD, Inc., MedicinNova, Inc., Millennium Pharma, Momenta Pharmaceuticals, Inc., NMD Pharma, Orion Pharma, PTC Therapeutics, Inc., Seelos Therapeutics, Inc., Seikagaku Corporation, UCB, and Viela Bio. SS: fees from AstraZeneca, argenx, and UCB. TR: fees and/or grant support from Alexion, Annexon Biosciences, argenx, 2024 American Journal of Managed Care – Institute for Value-Based Medicine, and UCB. BM: fees from argenx and AstraZeneca. MP: fees from Alexion, Amgen, Annexon, argenx, BVBA, Catalyst, CSL Behring, Grifols, Immunovant, Janssen, Momenta, Octapharma Pharmaceuticals, Takeda, and TerumoBCT. GSmall: fees received from Alexion. KG: fees received from Alexion, Amgen, argenx, Novartis, and UCB. CK: fees and/or grant support from Acceleron, Alpine, Alexion, Alnylam, Amgen, Amicus, Annexon, argenx, AstraZeneca, Corino, Biogen, CSL Behring, Genentech, Genzyme, Ionis, J&J, Neuroderm, Novo Nordisk, Octapharma, Pfizer, Sanofi, UCB, Takeda, Vertex, and Zai lab. GSahagian: fees and/or grant support from Alexion, argenx, Cartesian Therapeutics, Immunovant, NMD, Regeneron, and UCB. MHF: fees from argenx. CBT: fees and/or grant support from Alexion, argenx, Janssen, MGNet, Muscular Dystrophy Canada, Novartis, UCB, and the US Department of Defense. TM: fees and/or grant support from Alexion, Amicus, AnnJi, argenx, Arvinas, Ask Bio, Astellas Gene Therapeutics, AvroBio, BioCryst, Cabaletta, Cartesian Therapeutics, Fate Therapeutics, Grifols, Horizon Therapeutics, Immunovant, Maze Therapeutics, Merck, ML-Bio, Myositis Association, National Insititutes of Health, Neuromuscular Disease Foundation, NKarta, Poseida, Ra Pharmaceuticals, Regeneron, Shionogi, Momenta (now Janssen), Sanofi, Spark Therapeutics, UCB, and Valerion. JFH: fees and/or grant support from Academic CME, Ad Scientiam, Alexion/AstraZeneca Rare Disease, argenx, Biohaven Pharmaceuticals, Inc., Biologix Pharma, Cartesian Therapeutics, Centers for Disease Control and Prevention, MedScape CME, Merck EMB Serono, MGFA, Muscular Dystrophy Association, National Institutes of Health, NMD Pharma, Novartis, PeerView CME, Physicians’ Education Resource CME, PlatformQ CME, Regeneron, Sanofi, TG Therapeutics, Toleranzia AB, and UCB. MV, AP, AS, MB, and ZS have nothing to disclose.
This study was funded by Cartesian Therapeutics. Medical writing and editorial support was provided by Laura Graham, PhD, and Nick Gibbs of Ogilvy Health and Eva Rybak, PharmD, of Cartesian Therapeutics.
Author disclosures
This study was funded by Cartesian Therapeutics. HK, MK, CMJ, and MDM are employed by, and may hold stocks in, Cartesian Therapeutics. TV: associations with and fees received from Alexion/AstraZeneca Rare Disease, Amgen, argenx, Cartesian Therapeutics, COUR, CSL Behring, Dianthus Therapeutics, EMD Serono, ImmunAbs, Immunovant, Johnson & Johnson, NMD Pharma, Regeneron, and UCB. HDT: fees from Alexion and UCB. MR: fees and/or grant support from Alexion, Amylyx, Apellis Pharma, argenx, Biohaven Pharmaceuticals, Inc., Cartesian Therapeutics, Catalyst Pharmaceuticals, Cytokinetics, Inc., Grifols, Healey Center, Janssen Research and Development, Mallinckrodt ARD, Inc., MedicinNova, Inc., Millennium Pharma, Momenta Pharmaceuticals, Inc., NMD Pharma, Orion Pharma, PTC Therapeutics, Inc., Seelos Therapeutics, Inc., Seikagaku Corporation, UCB, and Viela Bio. SS: fees from AstraZeneca, argenx, and UCB. TR: fees and/or grant support from Alexion, Annexon Biosciences, argenx, 2024 American Journal of Managed Care – Institute for Value-Based Medicine, and UCB. BM: fees from argenx and AstraZeneca. MP: fees from Alexion, Amgen, Annexon, argenx, BVBA, Catalyst, CSL Behring, Grifols, Immunovant, Janssen, Momenta, Octapharma Pharmaceuticals, Takeda, and TerumoBCT. GSmall: fees received from Alexion. KG: fees received from Alexion, Amgen, argenx, Novartis, and UCB. CK: fees and/or grant support from Acceleron, Alpine, Alexion, Alnylam, Amgen, Amicus, Annexon, argenx, AstraZeneca, Corino, Biogen, CSL Behring, Genentech, Genzyme, Ionis, J&J, Neuroderm, Novo Nordisk, Octapharma, Pfizer, Sanofi, UCB, Takeda, Vertex, and Zai lab. GSahagian: fees and/or grant support from Alexion, argenx, Cartesian Therapeutics, Immunovant, NMD, Regeneron, and UCB. MHF: fees from argenx. CBT: fees and/or grant support from Alexion, argenx, Janssen, MGNet, Muscular Dystrophy Canada, Novartis, UCB, and the US Department of Defense. TM: fees and/or grant support from Alexion, Amicus, AnnJi, argenx, Arvinas, Ask Bio, Astellas Gene Therapeutics, AvroBio, BioCryst, Cabaletta, Cartesian Therapeutics, Fate Therapeutics, Grifols, Horizon Therapeutics, Immunovant, Maze Therapeutics, Merck, ML-Bio, Myositis Association, National Insititutes of Health, Neuromuscular Disease Foundation, NKarta, Poseida, Ra Pharmaceuticals, Regeneron, Shionogi, Momenta (now Janssen), Sanofi, Spark Therapeutics, UCB, and Valerion. JFH: fees and/or grant support from Academic CME, Ad Scientiam, Alexion/AstraZeneca Rare Disease, argenx, Biohaven Pharmaceuticals, Inc., Biologix Pharma, Cartesian Therapeutics, Centers for Disease Control and Prevention, MedScape CME, Merck EMB Serono, MGFA, Muscular Dystrophy Association, National Institutes of Health, NMD Pharma, Novartis, PeerView CME, Physicians’ Education Resource CME, PlatformQ CME, Regeneron, Sanofi, TG Therapeutics, Toleranzia AB, and UCB. MV, AP, AS, MB, and ZS have nothing to disclose.
Summary & conclusions
Background
Myasthenia Gravis (MG) treatments that modulate upstream immune targets to eliminate the source of autoantibody production, such as BCMA-expressing plasma cells, have the potential to improve therapeutic durability and tolerability versus standard of care broad immunosuppressants.Purpose
A phase 2b study to assess the efficacy and safety of Descartes-08, an autologous, BCMA-targeted CAR T-cell product, versus placebo in adults with gMG using the MGC, MG-ADL, and QMG scores at Month 3.Methods
Adult patients with gMG eligible for inclusion in the phase 2b, double-blind, placebo-controlled trial were randomized 1:1 to receive either six once-weekly intravenous infusions of Descartes-08 or placebo in the outpatient setting with a 12-month follow-up period post infusion.Findings
Descartes-08 treatment resulted in greater reductions in mean MGC, MG-ADL, and QMG scores versus placebo at Month 3. 33% of participants in the overall population and 57% of participants with no prior exposure to complement or FcRn inhibitors achieved MG-ADL minimum symptom expression at Month 6, which was maintained through Month 12. Descartes-08 was well tolerated, with no reports of cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome.Conclusions
A single course of six once-weekly infusions of Descartes-08 administered in the outpatient setting resulted in robust and durable clinical responses through 12 months. Descartes-08 demonstrated a tolerable safety profile.
The pivotal phase 3 AURORA trial (NCT06799247) is currently enrolling to further evaluate the safety and efficacy of Descartes-08 in gMG.
BCMA, B-cell maturation antigen; CAR, chimeric antigen receptor; FcRn, fragment crystallizable receptor (neonatal); gMG, generalized myasthenia gravis; MG, myasthenia gravis; MG-ADL, Myasthenia Gravis Activities of Daily Living; MGC, Myasthenia Gravis Composite; mRNA, messenger ribonucleic acid; QMG, Quantitative Myasthenia Gravis.
Introduction
MG is an autoimmune condition characterized by chronic weakness and muscle fatigue.1,2
MG is driven by the secretion of autoantibodies from pathogenic BCMA-expressing plasma cells,3-5 which cause tissue destruction and reduce the functionality of defined antigens at the neuromuscular junction, including AChR.2,6
Modulating upstream immune targets that eliminate the source of autoantibody production, such as pathogenic BCMA-expressing plasma cells, has the potential to improve therapeutic durability and tolerability for patients with MG compared with existing therapies that broadly suppress the immune system.
Descartes-08 is an autologous, BCMA-targeted, mRNA CAR T-cell product administered in the outpatient setting without pre-treatment chemotherapy.5
In a phase 1b/2a open-label study in patients with gMG, a single course of six once-weekly infusions of Descartes-08 resulted in robust and durable clinical responses through 12 months of follow-up with a favorable safety profile.5
MG is driven by the secretion of autoantibodies from pathogenic BCMA-expressing plasma cells,3-5 which cause tissue destruction and reduce the functionality of defined antigens at the neuromuscular junction, including AChR.2,6
Modulating upstream immune targets that eliminate the source of autoantibody production, such as pathogenic BCMA-expressing plasma cells, has the potential to improve therapeutic durability and tolerability for patients with MG compared with existing therapies that broadly suppress the immune system.
Descartes-08 is an autologous, BCMA-targeted, mRNA CAR T-cell product administered in the outpatient setting without pre-treatment chemotherapy.5
In a phase 1b/2a open-label study in patients with gMG, a single course of six once-weekly infusions of Descartes-08 resulted in robust and durable clinical responses through 12 months of follow-up with a favorable safety profile.5
AChR, acetylcholine receptor; BCMA, B-cell maturation antigen; CAR, chimeric antigen receptor; gMG, generalized myasthenia gravis; MG, myasthenia gravis; mRNA, messenger ribonucleic acid.
- McCallion J, et al. BMC Neurol. 2024;24:61.
- Koneczny I, et al. Cells. 2019;8:671.
- Zografou C, et al. Front Immunol. 2021;12:686466.
- Jin W, et al. Cell Discov. 2021;7:85.
- Granit V, et al. Lancet Neurol. 2023;22:578‑90.
- Kohler S, et al. J Neuroimmunol. 2013;264:114‑9.
Objective
To assess the efficacy of Descartes-08 versus placebo in adults with gMG using the MGC, MG-ADL, and QMG scores at Month 3.
gMG, generalized myasthenia gravis; MG-ADL, Myasthenia Gravis Activities of Daily Living; MGC, Myasthenia Gravis Composite; QMG, Quantitative Myasthenia Gravis.
Methods
Study design
Figure 1. Eligible patients included in the phase 2b, double-blind, placebo-controlled trial were randomized 1:1 to receive either six once-weekly intravenous infusions of Descartes-08 or placebo with a 12-month follow-up period post infusion
*Patients underwent leukapheresis for Descartes-08 manufacturing purposes ahead of randomization.
†During open-label extension, follow-up for patients randomized to the placebo to Descartes-08 crossover treatment cohort occurred at Months 3, 4, 6, 9, and 12 post infusion; follow-up for those randomized to the Descartes-08 cohort occurred at Months 4, 6, 9, and 12.
Patients eligible for inclusion were those with MG-ADL score ≥6, MGFA Class II–IV, and non-MuSK+ gMG. Permitted concomitant medications were pyridostigmine, corticosteroids (≤40 mg prednisone daily or equivalent), azathioprine, mycophenolate mofetil, and complement inhibitors, provided a stable dose at least 8 weeks prior to first infusion.
Study endpoints
Primary endpoint
The proportion of patients achieving a ≥5-point decrease in MGC at Month 3 compared with baseline.Secondary endpoints
Mean change from baseline in MG-ADL and QMG scores at each post-infusion visit.Safety and tolerability of Descartes-08 in patients with gMG.
Statistical analyses
Analyses were performed on the overall patient population, which comprised per-protocol (PP) and modified intention-to-treat (mITT) patients (those enrolled at academic centers with at least one follow-up).Two subgroup analyses were performed to assess the efficacy and durability of Descartes-08 in i) AChR+ patients, and ii) those with no prior exposure to complement or FcRn inhibitors.
Two independent sample tests for equality of proportions were used for the primary endpoint; Mann–Whitney U test and descriptive statistics were used for the secondary endpoints.
AChR+, positive for autoantibodies against the acetylcholine receptor; FcRn, fragment crystallizable receptor (neonatal); gMG, generalized myasthenia gravis; MG-ADL, Myasthenia Gravis Activities of Daily Living; MGC, Myasthenia Gravis Composite; MGFA, Myasthenia Gravis Foundation of America; mITT, modified intention-to-treat; MuSK+, positive for autoantibodies against muscle-specific tyrosine kinase; QMG, Quantitative Myasthenia Gravis.
Baseline characteristics
Demographics, baseline disease characteristics, and prior and ongoing treatments were comparable between treatment cohorts.
Table 1. Patient characteristics and demographics
*p<0.05.
Table 2. Prior and ongoing treatments
AChR+, positive for autoantibodies against the acetylcholine receptor; FcRn, fragment crystallizable receptor (neonatal); IVIg, intravenous immunoglobulin; LRP4+, positive for autoantibodies against the lipoprotein-4 receptor; MG, myasthenia gravis; MG-ADL, Myasthenia Gravis Activities of Daily Living; MGC, Myasthenia Gravis Composite; MGFA, Myasthenia Gravis Foundation of America; MV, mechanical ventilation; SD, standard deviation; sero, serotype; SoC, standard of care.
Efficacy
Descartes-08 demonstrated robust and durable clinical responses through 12 months
Data cut as of April 5, 2025.
Figure 2. The proportion of MGC score responders (≥5‑point score reduction) was significantly higher in the Descartes-08 cohort versus placebo at Month 3 in both the overall (A) and AChR+ (B) populations
PP population.
The mean reduction in MG-ADL score at Month 3 was also higher for the Descartes-08 treatment cohort versus placebo for both the overall (‑4.0 versus ‑1.7) and AChR+ (‑3.4 versus ‑0.9) patient populations (data not shown).
83% of participants treated with Descartes-08 maintained a clinically meaningful response in MG-ADL at Month 12.
33% of patients achieved MG-ADL minimum symptom expression at Month 6, which was sustained through Month 12.
Nine patients receiving Descartes-08 were on background prednisone at baseline (median 20 mg/day; range 5–25 mg), with the dose decreasing by 55% (median 9 mg/day; range 2.5–20 mg) at the last follow-up visit.
100% of participants treated with Descartes-08 reaching Month 12 maintained clinically meaningful response.
57% of patients achieved minimum symptom expression at Month 6, which was sustained through Month 12.
Figure 3. Mean reduction in MG-ADL (A) and QMG (B) scores was greater with Descartes-08 versus placebo at Month 3, with further deepening at Month 4, which was maintained through Month 12
mITT population: Descartes-08, n=15 D1 to M3, and n=12 M4 to M12 (three patients lost to follow-up); placebo, n=11 D1 to M3. Vertical dashed line shows end of six once-weekly infusions; white shaded area represents open-label follow-up period. Clinically meaningful decrease was defined as a ≥2-point reduction in MG-ADL score or a ≥3-point reduction in QMG score. Minimum symptom expression was defined as an MG-ADL score of 0 or 1.
83% of participants treated with Descartes-08 maintained a clinically meaningful response in MG-ADL at Month 12.
33% of patients achieved MG-ADL minimum symptom expression at Month 6, which was sustained through Month 12.
Nine patients receiving Descartes-08 were on background prednisone at baseline (median 20 mg/day; range 5–25 mg), with the dose decreasing by 55% (median 9 mg/day; range 2.5–20 mg) at the last follow-up visit.
Figure 4. All MG-ADL subscale component scores were equally improved with Descartes-08 versus placebo at Month 3
mITT population: Descartes-08, n=15; placebo, n=11.
Figure 5. Descartes-08 was associated with a robust and durable reduction in mean MG-ADL (A) and QMG (B) scores through 12 months in patients with no prior exposure to complement or FcRn inhibitors
mITT population: Descartes-08, n=9 at M3, n=7 at M4 (two patients lost to follow-up), and n=7 M6 to M12. Vertical dashed line shows end of six once-weekly infusions; white shaded area represents open-label follow-up period. Clinically meaningful decrease was defined as a ≥2-point reduction in MG-ADL score or a ≥3-point reduction in QMG score. Minimum symptom expression was defined as an MG-ADL score of 0 or 1.
100% of participants treated with Descartes-08 reaching Month 12 maintained clinically meaningful response.
57% of patients achieved minimum symptom expression at Month 6, which was sustained through Month 12.
Safety
Descartes-08 demonstrated a well-tolerated safety profile
There were no reports of cytokine release syndrome (CRS) or immune effector cell–associated neurotoxicity syndrome (ICANS).
There was no increased risk of infections with Descartes-08 versus placebo.
There were no AEs reported after Month 3 post infusion.
Table 3. The most commonly observed treatment-emergent adverse events through Month 3 for the Descartes-08 treatment cohort were chills, headache, fever, and nausea, which typically resolved 24 hours post infusion
AEs with a cumulative incidence of ≥15%. Total AEs reported through Month 3 for placebo-treated patients and through Month 12 for Descartes-08-treated patients. Safety dataset comprises all patients who received at least one dose of Descartes-08 or placebo.
There were no reports of cytokine release syndrome (CRS) or immune effector cell–associated neurotoxicity syndrome (ICANS).
There was no increased risk of infections with Descartes-08 versus placebo.
There were no AEs reported after Month 3 post infusion.
Figure 6. There were no observed changes in circulating CD19+ B cells up to 90 days post infusion (A) or in IgG levels at Day 85 versus Day 1 (B)
For panel A, data at each time point represent mean±SEM for all patients (n=35). For panel B, data are individual values, median, range, and IQR (n=26).
Figure 7. There was no significant change from baseline in common vaccine titers at primary endpoint (Day 85) for patients treated with Descartes-08 or placebo
Data indicate change in vaccine titers for each participant in the mITT group (n=26) at Day 85 relative to Day 1. Data are individual values, median, range, and IQR. Additional analyses demonstrated no differences between Descartes-08 and placebo for anti-men sero C, anti-men sero W135, anti-men sero Y, anti-diphtheria, anti-measles, anti-mumps, and anti-rubella titers (data not shown).
AE, adverse event; CD19, cluster of differentiation 19; D, day; IgG, immunoglobulin G; IQR, interquartile range; men, meningococcal; mITT, modified intention-to-treat; sero, serotype; SEM, standard error of the mean; VZV, varicella zoster.
Additional resources
Contact us
For queries about this poster or the phase 3 AURORA trial (NCT06799247), please contact us at: medicalaffairs@cartesiantx.com
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