To compare the effects of Descartes-08 in biologic non-responsive and biologic naive patients with generalized myasthenia gravis (gMG).

Descartes-08 is an autologous, BCMA-directed mRNA chimeric antigen receptor (CAR) T-cell therapy designed for outpatient administration without lymphodepleting chemotherapy. In a Phase 2b randomized study, treatment with Descartes-08 resulted in significant improvements in MG severity scores compared to placebo. This post-hoc analysis examined the impact of prior biologic drug exposure on outcomes.

Adults with non-MuSK+ gMG and MG-ADL ≥6 requiring immunosuppression were randomized 1:1 to receive six once-weekly infusions of Descartes-08 or placebo. For this post-hoc analysis, participants with exposure to CD20-targeting drugs, FcRn or complement inhibitors were deemed “biologic non-responders." Efficacy endpoints included mean change from baseline in MG-ADL and QMG scores at Month 3 through Month 12. Additional analyses explored serum cytokines as immune biomarkers of treatment response.

In the modified intent-to-treat population, 15 participants were randomized to Descartes-08 and 11 to placebo. In the biologic naive population (n=14), mean (SD) reduction in MG-ADL and QMG at Month 3 was -5.2(1.1) and -5.0(1.3) (Descrartes-08) versus -3.0(2.1) and -4.0(1.8) (placebo), respectively, and improved further at Month 12 (MG-ADL -7.1[1.9] and QMG -9.4[2.6]). In biologic non-responsive patients (n=12), mean (SD) reduction in MG-ADL and QMG at Month 3 was -2.5(1.3) and -2.2(2.0) (Descartes-08) versus -0.5(1.4) and 0.5(1.4) (placebo) and at Month 12, -2.0(0.7) and -3.0(1.9), respectively. Post-infusion differences in several key cytokines were noted between the two groups. Infusion-related reactions were the most common adverse events, with no cytopenia, infections, hypogammaglobulinemia, CRS or ICANS.

Both biologic non-responders and the biologic naive participants had greater improvement in MG efficacy measures after Descartes-08 compared to placebo, with greater depth of response in the biologic naive group. Changes in key cytokines may underpin the differential response.