Cartesian Therapeutics, Inc. (NASDAQ: RNAC) has announced that it has received agreement from the U.S. Food and Drug Administration (FDA) under the Special Protocol Assessment (SPA) process on the overall design of its planned Phase 3 AURORA trial for Descartes-08 in myasthenia gravis (MG).
The SPA agreement indicates that the FDA has determined that the proposed trial design is acceptable to support a future Biologics License Application for Descartes-08 in MG, subject to the ultimate outcome of the trial. The Phase 3 AURORA trial is set to commence in the first half of 2025.
Phase 3 AURORA Trial Design
The Phase 3 AURORA trial is a randomized, double-blind, placebo-controlled study designed to evaluate Descartes-08 against placebo. Approximately 100 participants with acetylcholine receptor autoantibody positive (AChR Ab+) MG will be enrolled and randomized 1:1 to receive either Descartes-08 or placebo. The treatment will be administered as six once-weekly infusions without preconditioning chemotherapy. The primary endpoint will assess the proportion of Descartes-08 participants with an improvement in MG Activities of Daily Living (MG-ADL) score of three points or more at Month 4 compared to placebo.
Positive Phase 2b Results
In December 2024, Cartesian Therapeutics announced positive updated results from the Phase 2b trial of Descartes-08 in participants with MG. The data showed deepening responses over time, with Descartes-08-treated participants in the primary efficacy dataset (n=12) experiencing an average MG-ADL reduction of 5.5 (±1.1) at Month 4. The treatment was well-tolerated, supporting outpatient administration without the need for lymphodepleting chemotherapy.
Myasthenia Gravis and Descartes-08
Myasthenia gravis (MG) is a chronic autoimmune disorder characterized by muscle weakness and fatigue. In most MG patients, the disease is driven by antibodies against the acetylcholine receptor, a protein crucial for nerve-muscle communication. Current treatments typically involve chronic immunosuppressive medications, which carry risks and side effects.
Descartes-08 is an autologous mRNA-engineered chimeric antigen receptor T-cell therapy (mRNA CAR-T) targeting B-cell maturation antigen (BCMA). It is currently in clinical development for generalized myasthenia gravis (MG) and systemic lupus erythematosus. Unlike traditional DNA-based CAR T-cell therapies, Descartes-08 is designed to be administered without preconditioning chemotherapy, in an outpatient setting, and without the risk of genomic integration. The FDA has granted Descartes-08 Orphan Drug Designation and Regenerative Medicine Advanced Therapy Designation for MG, as well as Rare Pediatric Disease Designation for juvenile dermatomyositis.
Expert Commentary
Carsten Brunn, Ph.D., President and Chief Executive Officer of Cartesian Therapeutics, stated, "This SPA agreement marks an important milestone in the development of Descartes-08 for MG, providing critical regulatory clarity and a clear path toward potential approval. Supported by compelling Phase 2b results where we observed deep and durable improvements in patients with MG, we firmly believe that Descartes-08 has the potential to serve as a meaningful new therapy that can be delivered in the convenient outpatient setting without the need for preconditioning chemotherapy. We look forward to commencing the Phase 3 AURORA trial in the first half of this year."
