Cartesian heads to phase 3 with mRNA CAR-T therapy for myasthenia gravis

Cartesian Therapeutics shared updated efficacy and safety data from a phase 2b trial of its lead mRNA cell therapy candidate in generalized myasthenia gravis, outlining its plan to move into a phase 3 trial.

Descartes-08 is an autologous mRNA-engineered chimeric antigen receptor T cell therapy (mRNA CAR-T) product candidate targeting B cell maturation antigen (BCMA). The therapy, which can be administered in an outpatient setting, is designed to be administered without preconditioning chemotherapy and does not use integrating vectors.

According to Cartesian, current standards of care for myasthenia gravis, a rare and incurable autoimmune disorder, offer only broad immunosuppression and limited efficacy. 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. 

In addition to the positive long-term follow up data from the phase 2a trial that was shared back in January, Cartesian has now offered up positive updated results from retreated participants enrolled in the phase 2a open-label portion of the trial. According to Cartesian, two participants were previously retreated, and experienced rapid improvement in clinical scores and maintained minimum symptom expression for up to one year after receiving a second treatment cycle. A third participant received a second treatment cycle and at the participant’s month 2 visit, achieved a 4-point reduction in MG Activities of Daily Living (MG-ADL) score and 6-point reduction in MG Composite (MGC) score scores from baseline, without reports of cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS).

Cartesian also provided details on the design of its planned phase 3 trial of Descartes-08 in patients with MG, which will start in the first half of 2025. The randomized, double-blind, placebo-controlled phase 3 AURORA trial will assess Descartes-08 versus placebo administered as six weekly outpatient infusions without preconditioning chemotherapy in approximately 100 participants with acetylcholine receptor autoantibody positive (AChR Ab+) MG. The primary endpoint will assess the proportion of Descartes-08 participants with an improvement in MG-ADL score of three points or more at month 4 compared to placebo.