▎WuXiEdited by the Kant Content Team

Cartesian Therapeutics today announced the latest efficacy and safety data from its ongoing 2b trial of the investigational mRNA cell therapy Descartes-08 in treating patients with generalized myasthenia gravis (MG). Analysis shows that 80% of evaluable patients maintained a clinically significant response for up to one year. Detailed data were presented at the 2nd Annual Cell Therapy Summit for Autoimmune Diseases. The related phase 3 trial, AURORA, is expected to launch in the first half of 2025.

In this Phase 2b double-blind, placebo-controlled, crossover trial, a total of 36 severely symptomatic, heavily treated MG patients were randomized (1:1) Patients will receive weekly outpatient infusions of Descartes-08 or placebo for a total of 6 weeks, without pre-treatment chemotherapy.At the end of the blinded assessment in the third month of the trial, patients receiving placebo were eligible to switch to Descartes-08 treatment.

The primary efficacy endpoint assessed the proportion of patients with a reduction of 5 points or more in the Myasthenia Gravis Composite (MGC) score. Secondary endpoints evaluated safety, tolerability, and other validated MG severity scale metrics, including Activities of Daily Living (MG-ADL), Quantitative Myasthenia Gravis (QMG), and the MG Quality of Life Revised Scale (MG-QoL-15R).

▲Main Efficacy Results of Descartes-08 (Image Source: Reference [2])

The latest data analysis released this time is as follows:

• The patient's response gradually increased over time:In the primary efficacy dataset (n=12), the average MG-ADL score of patients decreased by 5.5 points (±1.1) at the fourth month.

• Patients who had not previously received biologic therapy showed more significant improvement:In the 4th month, patients (n=7) who had not received biologic therapies such as complement inhibitors or neonatal Fc receptor (FcRn) inhibitors showed an average reduction of 6.6 points (±1.5) in MG-ADL scores.

• Enhanced efficacy was observed at Month 6:In the primary efficacy dataset, 33% (4/12) of patients achieved minimal manifestation status (MG-ADL score of 0 or 1); among patients not receiving biologic therapy, this proportion was 57% (4/7).

• Efficacy persisted through Month 12:In the primary efficacy dataset, 80% (4/5) of evaluable patients maintained a clinically significant response with at least a 2-point reduction in MG-ADL score. Both patients who did not receive biologic therapy maintained significant efficacy, with one patient remaining in a state of minimal symptom expression.

• Descartes-08 is well tolerated:Supports outpatient administration without the need for lymphodepleting chemotherapy. Consistent with previously reported data, in the safety dataset (n=36), Descartes-08 was well-tolerated, with adverse events primarily being mild and transient. Notably, no cases of cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) were observed.

▲Descartes-08 Efficacy Lasts Up to 1 Year (Image Source: Reference [2])

Descartes-08 is a potential "first-in-class" autologous mRNA-engineered chimeric antigen receptor T-cell (mRNA CAR-T) therapy.It works by targetingBCellMature Antigen (BCMA), eliminating plasma cells that secrete autoantibodies.Compared with traditional DNA-based CAR-T cell therapy, the administration design of mRNA CAR-T cell therapy does not require pre-conditioning chemotherapy and has been observed to have predictable and controllable pharmacokinetics, allowing for outpatient administration while avoiding the risks of gene integration and cancer transformation.Descartes-08 has previously received the Regenerative Medicine Advanced Therapy (RMAT) designation and Orphan Drug designation from the U.S. FDA for the treatment of MG.

References:

[1] Cartesian Therapeutics Announces Positive Updated Results from Phase 2b Trial of Descartes-08 in Participants with Myasthenia Gravis and Outlines Design of Planned Phase 3 Trial. Retrieved December 3, 2024 from https://ir.cartesiantherapeutics.com/news-releases/news-release-details/cartesian-therapeutics-announces-positive-updated-results-phase

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