Cartesian Therapeutics announced positive topline results from its Phase 2b trial of Descartes-08 in patients with generalized myasthenia gravis (MG). The trial met its primary endpoint with statistical significance, demonstrating the potential of Descartes-08 as a novel treatment for this debilitating autoimmune disorder. The company expects to hold an End-of-Phase 2 meeting with the FDA by year-end.
Primary Endpoint Achieved
The Phase 2b trial was a double-blind, placebo-controlled, crossover study involving 36 heavily pre-treated patients with MG. Patients were randomized 1:1 to receive either Descartes-08 or placebo as six weekly outpatient infusions, without preconditioning chemotherapy. The primary efficacy endpoint was the proportion of patients with a reduction of five points or more in the MG Composite (MGC) score at Month 3.
The trial achieved its primary endpoint in the pre-specified modified intent-to-treat (mITT) efficacy population. 71% (10/14) of patients treated with Descartes-08 showed a 5-point or greater improvement in MGC score at Month 3, compared to 25% (3/12) of patients treated with placebo (p=0.018). The trial also achieved its primary endpoint with statistical significance in the per-protocol population, with 69% (11/16) of patients treated with Descartes-08 observed to have 5-point or greater improvements in MGC score at Month 3 compared to 33% (5/15) of patients treated with placebo (p=0.048).
Secondary Endpoints and Safety
Consistent with previous results from the Phase 2a open-label portion of the trial, Descartes-08 responders experienced deep improvements across MG severity scales at Month 3 (average MG-ADL = -5.6; MGC= -8.3; QMG = -5.0; QoL-15r = -7.9). These improvements persisted or further improved in patients evaluated at their Month 4 (n=5) and Month 6 (n=3) follow-up visits.
Descartes-08 continues to demonstrate a favorable safety profile, supporting outpatient administration without the need for lymphodepleting chemotherapy. The therapy was well-tolerated, with adverse events being transient and mostly mild. Notably, there were no cases of cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome.
Updated Phase 2a Open-Label Trial Results
Updated results from two patients enrolled in the Phase 2a open-label portion of the trial showed rapid improvement in clinical scores and maintained minimal symptom expression for up to one year after receiving a second treatment cycle. The time course and magnitude of treatment response upon retreatment were similar to those seen when the patients were first treated. Four of the seven patients from the Phase 2a portion of the trial maintained clinically meaningful responses for at least one year following initial dosing.
Implications for Myasthenia Gravis Treatment
Myasthenia gravis is a chronic autoimmune disorder characterized by muscle weakness and fatigue. Current treatments often involve chronic immunosuppressive medicines, which carry risks and side effects. Descartes-08 offers a potential short-course treatment option with a favorable safety profile, addressing a significant unmet need in MG management.
"We believe the positive data presented today demonstrate clinical proof-of-concept of our novel mRNA platform and highlight the potential of Descartes-08 to provide deep and durable improvements for patients with MG," said Carsten Brunn, Ph.D., President and Chief Executive Officer of Cartesian.
Ongoing Research and Future Directions
Cartesian has an ongoing double-blind randomized control trial of Descartes-08 in MG, with topline data expected in the middle of this year. The company also has an investigational new drug allowance for Descartes-08 for systemic lupus erythematosus and is on track to dose the first patient in the first half of this year. These efforts underscore Cartesian's commitment to expanding the application of mRNA cell therapy to other autoimmune diseases.
