RARE Daily

Cartesian Reports Positive Long-Term Follow-Up of Phase 2 mRNA Cell Therapy Data in MG

January 9, 2024

Rare Daily Staff

Cartesian Therapeutics reported positive 12-month follow-up data from its Phase 2a trial of Descartes-08 in patients with generalized myasthenia gravis, a rare and chronic autoimmune disease.

MG is a chronic autoimmune disorder that causes disabling muscle weakness and fatigue. For most people with MG, the disease is characterized by the presence of antibodies against the acetylcholine receptor, a protein found on the surface of nerve cells that plays a key role in muscle contraction. There is currently no cure for MG, and treatment typically requires chronic immunosuppressive medicines, with their attendant risks and side effects.

Descartes-08 is a first-in-class, rCAR-T in clinical development for MG and other autoimmune diseases. Compared to conventional DNA-based CAR T-cell therapies, rCAR-T has predictable and controllable pharmacokinetics and avoids the risk of genomic integration. These attributes are expected to make Descartes-08 safer than DNA-based cell therapies. Descartes-08 is a personalized (autologous) therapy during which cells are collected, engineered with RNA, and returned to the same individual in the outpatient setting. A course of therapy consists of six weekly infusions.

Descartes-08 has been granted Orphan Drug Designation by the U.S. Food and Drug Administration for the treatment of MG, and Investigational New Drug (IND) allowance to begin trials in patients with an additional autoimmune disease, lupus.

“The 12-month data build on the positive data reported earlier this year in The Lancet Neurology, underscoring the potential of Descartes-08 to drive deep and durable responses in patients with MG,” said Milos Miljkovic, chief medical officer of Cartesian Therapeutics. “Notably, most patients maintained robust, clinically meaningful improvements across all four standard MG severity scores approximately 10 months after the last infusion. In addition, the lasting reductions in autoantibody titers are consistent with the observed clinical responses and the proposed mechanism of action for Descartes-08, supporting the deep and long-lasting effects observed in the study.”

He said as the first clinical trial using mRNA CAR-T to treat autoimmunity, the study also highlights the potential of Cartesian’s approach to expand the capabilities of cell therapy to address a variety of autoimmune diseases.

The company previously announced positive data from a phase 1b/2a study of 14 patients with MG who received Descartes-08 in the outpatient setting and without lymphodepletion. In that dataset, Descartes-08 was observed to be safe and well-tolerated and was observed to induce deep and durable responses.

New, long-term results from all participants who received a once-weekly infusion for six weeks during the phase 2a portion of the study showed Descartes-08 was well-tolerated, with no dose-limiting toxicities, cytokine release syndrome, or neurotoxicity.

At month nine follow-up, all participants continued to experience marked and long-lasting clinical improvements across four validated MG disease scoring systems: MG Composite, MG Activities of Daily Living, Quantitative MG scores, and Quality of Life 15-revised. These assessments occurred approximately seven months after the last Descartes-08 infusion, and no participants received new or increased MG-directed drugs during the study period.

At Month 12, five of the seven participants maintained clinically meaningful improvement in the same four scoring systems. These assessments occurred approximately 10 months after the final Descartes-08 infusion.

Two participants experienced loss of clinical effect at Month 12 and were eligible for retreatment. One participant was retreated, and experienced rapid improvement in clinical scores, which was ongoing at Month six of follow-up with minimal symptom expression.

All three participants with detectable anti-acetylcholine receptor (AChR) antibody levels at baseline experienced marked anti-AChR antibody reductions by Month six, which deepened further by Month nine, and were maintained at Month 12.

Enrollment is ongoing in a phase 2b randomized, double-blind, placebo-controlled trial in patients with MG. Topline results are expected in mid-2024.

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