Phase 2b Myasthenia Gravis RNA CAR-T Trial Doses First Patient

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Cartesian Therapeutics’ Descartes-08 will be administered as 6 weekly infusions and does not require preconditioning chemotherapy.

The first patient has been dosed in a phase 2b randomized controlled trial (RCT) (NCT04146051) evaluating Cartesian Therapeutics’ Descartes-08, an investigational autologous RNA-engineered chimeric antigen receptor T-cell therapy (rCAR-T), for the treatment of myasthenia gravis (MG).1

Descartes-08 is comprised of patients’ own T-cells that have been modified ex-vivo with RNA to target B-Cell Maturation Antigen (BCMA). The use of RNA engineering is intended to avoid risks of genomic integration associated with DNA-based CAR-T therapies and to allow for control of pharmacokinetics. Descartes-08 was previously evaluated in the non-randomized phase 1/2a portion of the clinical trial, interim results from which were reported at the 14th Myasthenia Gravis Foundation of America (MGFA) International Conference on Myasthenia and Related Disorders, taking place in Miami, Florida, May 10-12, 2022.2 The data included participants showing at least 1 full class of improvement in MGFA clinical classification and a 50% mean improvement on the Myasthenia Gravis Composite Scale at 3 months after treatment. In terms of safety, it was reported that Descartes-08 was generally well-tolerated and that no cytokine release syndrome or other treatment-related adverse events (AEs) had occurred.

“As a physician who treats patients with myasthenia, I have been impressed by the magnitude and duration of responses seen in the phase 2a trial of Descartes-08 in MG,” Tahseen Mozaffar, MD, professor of neurology at University of California, Irvine, said in a statement regarding the news.1 “A tantalizing observation is that, after a 6-week course of Descartes-08, clinical responses continue to persist for many months and counting. RCTs are the gold standard for clinical trials, and I commend Cartesian for further studying Descartes-08 with this rigorous design.”

The multicenter, placebo-controlled trial is expected to enroll approximately 30 patients aged 18 years or older with generalized MG for whom immunosuppressive drugs have been deemed necessary by the trial’s investigator. The trial includes seronegative patients and excludes patients who are pregnant, lactating, or have a major chronic illness that is not well managed and deemed to increase the risk of participation.

Descartes-08 will be administered as 6 weekly infusions and will not require preconditioning chemotherapy. Patients who initially receive treatment with the placebo will have the opportunity to crossover to treatment with Descartes-08 later on. The trial’s primary end point is the proportion of patients achieving a 6 point or greater improvement in MG Activities of Daily Living score, assessed at 12 weeks. Secondary end points include comparisons of Descartes-08 versus the placebo on several MG assessments; comparisons of Descartes-08 versus the placebo on MG assessments for patients who crossover; the change in titer of myasthenia specific autoantibody titers; and the effect of single or multiple infusions of Descartes-08 on patients measured by MG assessments. The trial is recruiting at locations in several US states and has an estimated completion date of December 1, 2023. Cartesian Therapeutics has stated that the trial is likely the first ever placebo-controlled clinical trial for an engineered cell therapy.

“We are excited to begin this RCT in patients with MG,” Miloš Miljković, MD, chief medical Officer, Cartesian Therapeutics, added to the statement.1 “A placebo-controlled design will provide a stringent evaluation of Descartes-08 efficacy while elucidating its mechanisms of action. This will result in important insights on treating MG and other autoantibody-mediated autoimmune diseases with Descartes-08.”

REFERENCES
1. Cartesian Therapeutics announces dosing of first participant in a phase 2b randomized clinical trial for generalized myasthenia gravis. News release. Cartesian Therapeutics. January 31, 2023. Accessed February 2, 2023. https://www.cartesiantherapeutics.com/2023/01/31/cartesian-therapeutics-announces-dosing-of-first-participant-in-a-phase-2b-randomized-clinical-trial/ 
2. Cartesian Therapeutics to Present Late-Breaking Data from Phase 1/2a Trial of RNA CAR T-cell Therapy in Patients with Generalized Myasthenia Gravis. News release. Cartesian Therapeutics. May 10, 2022. https://www.prnewswire.com/news-releases/cartesian-therapeutics-to-present-late-breaking-data-from-phase-12a-trial-of-rna-car-t-cell-therapy-in-patients-with-generalized-myasthenia-gravis-301543090.html 
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