Efficacy and Safety of Autologous BCMA-directed mRNA CAR T-Cell Therapy in Generalized Myasthenia Gravis: Results from a Phase 2b Randomized Placebo-controlled Trial
Tuan Vu1, Hacer Durmus Tekce2, Michael Rivner3, Sheetal Shroff4, Thomas Ragole5, Bennett Myers6, Mamatha Pasnoor7, George Small8, Chafic Karam9, Mithila Vullaganti10, Amanda Peltier11, Gregory Sahagian12, Marc Feinberg13, Carolina Barnett Tapia14, Zaeem Siddiqi15, Christopher Jewell16, Metin Kurtoglu16, Hafsa Kamboh16, Milos Miljkovic16, Tahseen Mozaffar17, James Howard18
1University of South Florida, 2Division Of Medical Sciences, Istanbul Medical Faculty, 3Augusta University, 4Houston Methodist Hospital, 5University of Colorado Department of Neurology, 6Dent Neurologic Institute, 7University of Kansas Medical Center, 8ANA, 9University of Pennsylvania, 10Tufts Medical Center, 11Vanderbilt University, 12Neurology Center of Southern California, 13South Florida Neurology Ass., 14University of Toronto, 15University of Alberta Hospital, 16Cartesian Therapeutics, 17University of California Irvine, 18University of North Carolina
Objective:
Compare the effect of Descartes-08 versus placebo, as measured by the change in MG Composite (MGC) score from baseline to Month 3. Secondary: compare the effect of Descartes-08 versus placebo on MG-ADL and other measures of disease activity.
Background:
Descartes-08 is an autologous, BCMA-directed mRNA chimeric antigen receptor T-cell therapy administered in an outpatient setting and without chemotherapy. In a phase 1/2 study in generalized myasthenia gravis (MG), six weekly infusions of 52.5x106 CAR+ cells/kg per infusion led to deep and durable improvements in MG severity scales.
Design/Methods:
A phase 2b double-blind randomized controlled trial comparing six weekly infusions of Descartes-08 or placebo (NCT04146051) in adults with non-MuSK+ MG who required immunosuppressive therapy and had MG-ADL ≥6. After leukapheresis and manufacturing of autologous product, participants were randomized 1:1. Primary endpoint was the proportion of participants achieving ≥5-point improvement in MGC at Month 3.
Results:
Of 31 participants in the per protocol analysis, 18 were randomized to Descartes-08 and 13 to placebo, receiving median 6 doses (range 2–6). There were significantly more responders in the active arm in the overall population (67% versus 31%) and the AChR antibody-positive population (64% versus 20%). Mean change in MGC at Month 3 was -5.6 (Descrartes-08) versus -0.5 (placebo) in the AChR+ and -5.4 versus -2.7 in the overall population, with placebo response more pronounced in the triple-seronegative population. Mean change in MG-ADL at Month 3 was -3.4 versus -0.9 (AChR+) and -3.8 versus -1.7 (overall). There was no cytokine release syndrome observed. The most common side effects reported in the Descartes-08 group but not in the placebo group were all infusion-related reactions resolving within 48 hours.
Conclusions:
Outpatient Descartes-08 administration was associated with significant reduction in disease activity scores compared to placebo with no concerning safety signals. Efficacy of Descartes-08 will be tested in a Phase 3 trial.
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.