
Pharmaceutical R&D Developer
▎Edited by the WuXi AppTec content team
Recently, Cartesian Therapeutics announced the results of its B-cell maturation antigen (BCMA)-targeted CAR-T therapy, Descartes-08, in treating myasthenia gravis (MG).
12-Month Follow-Up Data from Patient in Phase 2a Clinical Trial. The patient did not require lymphodepleting chemotherapy and achieved significant and sustained clinical improvements across four validated MG disease scoring systems.
The newly released data focus on the long-term outcomes from the Phase 2a stage of the trial, involving a total of 7 participants who received infusions once a week over a 6-week period during the study. The findings are as follows:
Descartes-08 was infused in an outpatient setting without the need for lymphodepleting chemotherapy. Throughout the study and long-term follow-up, Descartes-08 was well-tolerated, with no adverse events such as dose-limiting toxicity, cytokine release syndrome, or neurotoxicity.
At the 9-month follow-up, all subjects demonstrated significant and sustained clinical improvements across four validated MG disease rating systems, including the MG Composite Score, MG Activities of Daily Living Score, Quantitative MG Score, and the 15-item Quality of Life Revised Scale. These assessments were conducted approximately 7 months after the last infusion of Descartes-08, with no subjects receiving new or additional MG medications during the study period.
At Month 12, five of seven subjects maintained clinically meaningful significant improvements in the same four scoring systems. These assessments were conducted approximately 10 months after the last infusion of Descartes-08.
At the 12th month, two subjects experienced a decline in clinical efficacy and met the criteria for re-treatment. One of the subjects received re-treatment and showed rapid improvement in clinical scores, which persisted through the 6th month of follow-up, with the mildest symptoms observed.
Three subjects with detectable acetylcholine receptor (AChR) antibody levels at baseline showed a significant reduction in AChR antibody levels at Month 6, which became even more pronounced at Month 9 and was maintained at Month 12.
Currently, the research findings have been organized and published on the preprint platform medRxiv.
In the previously published Phase 1b/2a study, 14 patients with MG received Descartes-08 treatment in an outpatient setting without lymphodepletion preconditioning. In this dataset, Descartes-08 demonstrated good safety and tolerability and was able to induce deep and durable remission.
Descartes-08 is an mRNA cell therapy candidate and a potential “first-in-class” mRNA-engineered chimeric antigen receptor T-cell (mRNA CAR-T) therapy. It targets BCMA to eliminate plasma cells that secrete autoantibodies. Compared with traditional DNA-based CAR-T cell therapies, mRNA CAR-T cell therapy does not require pre-treatment chemotherapy in its administration design. It has been observed to possess predictable and controllable pharmacokinetics, enabling outpatient administration while avoiding the risks of genomic integration and cancer transformation.
Descartes-08 has been granted Orphan Drug Designation by the U.S. FDA for the treatment of MG, and has received FDA IND clearance to initiate clinical trials in patients with another autoimmune disease, lupus.
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