Cartesian achieves phase 2b autoimmune CAR-T success after endpoint adjustment

Cartesian Therapeutics recently announced a significant achievement in its phase 2b trial for its BCMA-directed CAR-T therapy, Descartes-08, targeting generalized myasthenia gravis (gMG). However, this success was reported after a change in the primary endpoint in May and the exclusion of a specific patient group.

The study included 36 participants who were randomly assigned to receive either Descartes-08 or a placebo. The primary endpoint analysis, however, focused only on 26 patients who were treated at academic medical centers and had at least one dose and one post-baseline assessment of the MG Composite (MGC) score. This change excluded nine patients treated at community clinics and one participant who dropped out.

Initially, the primary endpoint was based on the MG-ADL symptom scale, similar to studies by Argnex, Johnson & Johnson, and UCB. Cartesian switched to the MGC endpoint in May. Among the 26 patients analyzed, 10 of 14 who received Descartes-08 experienced a five-point or greater improvement in MGC after three months, compared to three of 12 in the placebo group. This resulted in a response rate difference of 71% versus 25%, meeting the trial's MGC endpoint in the modified intent-to-treat population.

Cartesian highlighted that a three-point change in MGC is typically considered clinically meaningful but opted for a more stringent five-point threshold based on previous study responses. The press release did not provide details on the three-point response comparison between Descartes-08 and the placebo.

The company also shared findings from a per-protocol population that included 31 patients. In this group, the MGC response rates were 69% for Descartes-08 and 33% for the placebo, with a p-value of 0.048, indicating statistical significance.

In addition to the primary efficacy analysis, Cartesian assessed changes from baseline in MG-ADL as a secondary endpoint. Patients receiving Descartes-08 showed a mean 5.6-point improvement in MG-ADL after three months. Initially, the placebo group showed similar improvements but fell behind after the first month, ending with less than a two-point improvement after three months.

The trial also revealed a significant imbalance in the proportion of participants with thymoma, a cancer linked to gMG. While 42% of the placebo group had thymoma, none in the Descartes-08 group did. There were also other numeric imbalances, including more placebo recipients having received complement inhibitors or FcRN drugs and having undergone thymus removal.

This development marks a major milestone for Cartesian since its Nasdaq listing through a reverse merger with Selecta Biosciences. The merger provided Cartesian with $110 million to advance its mRNA-based CAR-T therapy, which aims to reduce toxicity associated with DNA cell therapies and eliminate the need for preconditioning chemotherapy in autoimmune disorders.

As of March, Cartesian had nearly $105 million, which it expects to sustain operations until the second half of 2026. Alongside the phase 2b results, Cartesian announced plans to raise $130 million through a private investment in public equity, reinforcing its financial position for future developments.