BACKGROUND: Descartes-08 is an investigational autologous, BCMA-directed mRNA CAR T-cell therapy administered without pretreatment chemotherapy in the outpatient setting. In a phase 2b double-blind randomized controlled trial (RCT) in adults with non–muscle-specific kinase generalized myasthenia gravis (gMG) with baseline MG Activity of Daily Living (MG-ADL) score ≥6 and requiring immunosuppression, a single course of six once-weekly infusions of Descartes-08 led to significantly higher rates of clinical response compared to placebo (PBO) that were sustained up to last follow up at Month 12 (NCT04146051).
OBJECTIVES: Assess the effect of Descartes-08 versus PBO on MG Composite (MGC) score at month 3 and other disease activity measures in adults with acetylcholine receptor (AChR)+ gMG enrolled in the phase 2b RCT.
RESULTS: Nineteen of 26 patients randomized to the primary efficacy dataset were AChR+ and received Descartes-08 (n=11) or placebo (n=8). Response rates (a ≥ 5-point reduction in MGC at month 3) were significantly higher with Descartes-08 compared to PBO (63.6% versus 12.5%, p=0.0258). Further, patients who received Descartes-08 exhibited greater improvements in MGC score (mean reduction 5 versus 0.1), MG-ADL scores (3.4 versus 0.6) and QMG scores (mean reduction 3.6 versus 0.1) at month 3 relative to PBO. Reductions in MGC, QMG, and MG-ADL scores following Descartes-08 treatment were maintained through month 12 of follow up (mean reduction 6.7, 8.6, and 4.1, respectively). Notably, the most common adverse events reported in the Descartes-08 group were infusion-related reactions resolving within 48 hours.
CONCLUSIONS: Outpatient Descartes-08 administration was associated with clinically meaningful improvements in MGC and MG-ADL scores in patients positive for AChR autoantibodies with no concerning safety signals. A Phase 3 study is underway to further evaluate efficacy and safety (NCT06799247) in patients with AChR autoantibody-positive gMG.