Cartesian Therapeutics’ mRNA CAR-T Descartes-08 Shows Efficacy and Safety in Myasthenia Gravis in Phase 2 Study

Cartesian Therapeutics’ Descartes-08, an investigational autologous mRNA-engineered chimeric antigen receptor T-cell therapy (CAR-T) therapy that targets B-cell maturation antigen (BCMA), has demonstrated therapeutic effects in a phase 2b double-blind, placebo-controlled, crossover trial (NCT04146051) in myasthenia gravis (MG).¹ Sustained responses over a 12-month period were seen in treated patients, along with a safety profile that was aligned with previously reported data.

In the trial, heavily pretreated, highly symptomatic patients with MG (n = 36) were randomly assigned in a 1:1 fashion to undergo a 12-month treatment phase with either Descartes-08 or a placebo. Treatment with the CAR-T therapy, in the 12 patients who had available data, led to reductions of 5.5 (±1.1) and 4.8 (±1.4) in Myasthenia Gravis-Activities of Daily Living (MG-ADL) scores at 4 months and 12 months posttreatment, respectively. Furthermore, an average Quantitative Myasthenia Gravis Score (QMG) reduction of 4.8 (±1.7) points at 4 months posttreatment, which deepened through 12 months posttreatment (6.0 [±2.1]), was seen in these patients.

"This impressive data highlights the potential of Descartes-08 to serve as an important therapeutic option to deliver deep and sustained reductions in MG-ADL for patients with myasthenia gravis," trial investigator Tuan Vu, MD, a professor of neurology at the University of South Florida Morsani College of Medicine, and the director for Neuromuscular Medicine and EMG, said in a statement.¹ "The data in participants who had not received prior biologic therapy is particularly striking as this population is most comparable to the patient populations in trials of standard-of-care biologics."

"Participants in this subgroup who were randomized to Descartes-08 were observed to experience a profound average 7.1-point reduction in MG-ADL and 57% these patients were observed to maintain MSE out to Month 12," Vu continued. "I look forward to following the continued development of Descartes-08 in MG as it moves into the phase 3 AURORA trial."

No CAR-T therapies are currently approved for autoimmune disorders like MG, but the modality has become an emerging and promising option for investigation in the field. Unlike traditional DNA-based CAR-T therapies, Descartes-08 does not require preconditioning chemotherapy, is able to be administered in the outpatient setting, and does not come with the risk of genomic integration associated with cancerous transformation.

As of the March 31, 2025, cutoff date, the findings showed that 33% (4 of 12) of participants achieved minimum symptom expression (MSE), defined as an MG-ADL score of 0 or 1, at month 6, all of whom maintained MSE through month 12. After 12 months of treatment, 83% (10 of 12) of evaluable participants maintained a clinically meaningful response, defined as a reduction of at least 2 points in MG-ADL.

Participants without prior exposure to biologic therapies, including complement or FcRn inhibitors, showed more pronounced responses to Descartes-08 over 12 months, with average MG-ADL and QMG reductions of 7.1 (±1.9) and 9.4 (±2.6) points, respectively, by 12 months posttreatment. Notably, 57% (4 of 7) achieved MSE at Month 6, maintaining it through Month 12, while all participants (7 of 7) sustained at least a clinically meaningful response throughout the study.

During the 12-month study, Descartes-08 was deemed well-tolerated, with adverse events (AEs) that were transient and mostly mild, with no new AEs observed during that time. Notably, treatment with the CAR T-cell therapy yielded no events of cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome (ICANS), no decrease in vaccine titers for common viruses, and no increased rates of infection or hypogammaglobulinemia. Furthermore, there were no Descartes-08-related AEs reported in month 4 through month 12 follow-up.

"The remarkable results presented today underscore the potential of utilizing our cell therapy to deliver deep and durable responses in MG patients one year after receiving a single course of therapy in a convenient outpatient setting with no preconditioning chemotherapy," Carsten Brunn, PhD, president and chief executive officer at Cartesian, added to the statement.¹ "The impressive strength and duration of response shown in the data reinforce our confidence in the potential of Descartes-08 to transform the current treatment landscape in MG, offering patients a safe, flexible, and durable treatment option. We look forward to dosing the first patient in our phase 3 AURORA trial in the second quarter of this year."

The phase 3 AURORA trial, a follow-up study, is expected to begin in the second quarter of 2025. A few months ago, the FDA and Cartesian agreed on the overall design of the study, noting that it would be acceptable as evidence to support a future biologics license application, pending the outcomes of the trial. This randomized, double-blind, placebo-controlled trial is expected to include approximately 100 patients with acetylcholine receptor autoantibody positive MG who will be randomly assigned 1:1 to either Descartes-08 or placebo, administered as 6 once-weekly infusions without preconditioning chemotherapy. Investigators will use proportion of patients with an improvement of at least 3 points on MG-ADL score at month 4 as the primary end point.²

REFERENCES
1. Cartesian Therapeutics’ Descartes-08 Observed to Provide Deep and Sustained Benefits Through Month 12 After a Single Course of Therapy in Phase 2b Myasthenia Gravis Trial. News release. Cartesian Therapeutics. April 8, 2025. Accessed April 11, 2025. https://www.globenewswire.com/news-release/2025/04/08/3057465/0/en/Cartesian-Therapeutics-Descartes-08-Observed-to-Provide-Deep-and-Sustained-Benefits-Through-Month-12-After-a-Single-Course-of-Therapy-in-Phase-2b-Myasthenia-Gravis-Trial.html
2. Cartesian Therapeutics Announces FDA Special Protocol Assessment Agreement for Phase 3 AURORA Trial of Descartes-08 in Myasthenia Gravis. News release. Cartesian Therapeutics. January 27, 2025. Accessed April 11, 2025. https://ir.cartesiantherapeutics.com/news-releases/news-release-details/cartesian-therapeutics-announces-fda-special-protocol-assessment