Phase 3 trial of Descartes-08 in treating MG may launch in 2025
CAR T-cell therapy seen to ease severity of generalized MG in Phase 2 study
Cartesian Therapeutics is planning to launch a pivotal, Phase 3 clinical trial of its experimental cell therapy Descartes-08 in people with myasthenia gravis (MG), following positive data from an ongoing Phase 2 study in patients.
The company announced that it recently completed a meeting with the U.S. Food and Drug Administration (FDA) to discuss Phase 3 trial plans, which it expects to kick off in the first half of 2025. Details regarding the planned trial’s design, and further findings in the ongoing Phase 2b study are likely by year’s end, Cartesian stated in a company financial report.
“With a growing body of clinical evidence supporting the potential for Descartes-08 to serve as a meaningful addition to the MG treatment landscape, we are encouraged by our recent interaction with FDA regarding our plans for a Phase 3 program in MG,” said Carsten Brunn, PhD, Cartesian’s president and CEO.
Phase 3 trial is expected assess the CAR T-cell therapy in a larger MG group
MG is caused by B-cells, an immune system cell, producing antibodies that interfere with communication between nerve and muscle cells, resulting in disease symptoms marked by muscle weakness and fatigue.
Descartes-08 is an autologous chimeric antigen receptor (CAR) T-cell therapy that aims to ease MG severity by depleting or lowering the number of antibody-producing B-cells. With this type of therapy, T-cells — an immune cell group able to target other cells — are collected from a patient. These T-cells then are engineered with a special chimeric antigen receptor or CAR, which directs them to bind to and attack B-cells containing a surface protein called the B-cell maturation antigen. The engineered T-cells are infused back to the patient, with the goal of depleting B-cells producing the self-reactive antibodies.
Unlike conventional CAR T-cell therapies that use DNA to insert CARs into T-cells, Descartes-08 uses messenger RNA — a molecule that serves as a template for protein production. This is expected to enable Descartes-08 to be given without chemotherapy, a required pretreatment with DNA-based CAR T-cell therapies to wipe out existing immune cells before the engineered ones can be infused.
Earlier this year, Cartesian reported positive top-line data from the Phase 2b part of its Phase 1/2 MG-001 clinical trial (NCT04146051) testing Descartes-08 in people with generalized MG.
Generalized MG severity, antibody levels seen to fall with treatment in trial
In its Phase 2b part, 36 patients were treated with Descartes-08 or given a placebo over six weeks. Three months later, results showed that 71% of treated patients experienced a clinically meaningful reduction in disease severity, as seen in changes in MG Composite scores, compared with 25% of those on a placebo.
Phase 2b data also indicated that Descartes-08 led to lower levels of anti-acetylcholine receptor antibodies, the most common MG-driving antibody. The treatment was reported to have a generally favorable safety profile, with most adverse events being mild or temporary, supporting its administration in an outpatient setting without the need for chemotherapy.
Updated safety and efficacy findings from the trial’s Phase 2b part could be available shortly.
“For our lead Descartes-08 program in MG, we expect to share additional data from our Phase 2b trial and the design of our upcoming Phase 3 trial by the end of the year,” Brunn said.
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