Cartesian Therapeutics’ mRNA CAR-T Descartes-08 Produces Durable Responses in Myasthenia Gravis
Alongside the updated data, Cartesian announced that it plans to launch a phase 3 clinical trial, dubbed AURORA, in the first half of next year.
Cartesian Therapeutics’ Descartes-08, an investigational autologous mRNA-engineered chimeric antigen receptor T-cell therapy (CAR-T) therapy for the treatment of autoimmune diseases including myasthenia gravis (MG), has produced durable responses in some patients with MG treated in the phase 2b portion of a clinical trial (NCT04146051).1
Cartesian announced efficacy findings for the group of patients in the trial treated with at least 1 dose of Descartes-08 who had at least 3 months of follow-up, which constitutes the primary efficacy dataset. For the 12 patients in this group who had at least 4 months of follow-up, the average MG Activities of Daily Living (MG-ADL) score had reduced by 5.5 (±1.1) at 4 months posttreatment. For the 7 patients within this group who had not previously been treated with biologic therapies the average reduction in MG-ADL score was 6.6 (±1.5). Furthermore, at 6 months posttreatment, an MG-ADL score of 0 or 1 was achieved by 4 of 12 patients (33%) in the primary efficacy dataset and 4 of 7 patients (57%) in the group of patients who had not previously received biologic therapy. For the 5 patients in the primary efficacy dataset who reached 12 months of follow-up, 4 patients (80%) maintained at least a 2 point reduction in MG-ADL score, which was considered a clinically meaningful response. Both of the only 2 patients who had not previously received biologic therapy and reached 12 months of follow-up maintained such a clinically meaningful response, with 1 of these patients maintaining an MG-ADL score in the range for minimum symptom expression (0 to 1).
The safety data set for the trial includes 36 patients, and Cartesian characterized Descartes-08 as “well-tolerated” in this group, with adverse events being “transient and mostly mild.” No cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome occurred in any of the patients, and Descartes-08 was not associated with increased rates of infection or hypogammaglobulinemia. In addition, the CAR-T did not appear to cause vaccine titers for common viruses to decrease.
“Current standards of care are associated with broad immunosuppression and limited efficacy, and patients with MG, which is a rare and incurable autoimmune disorder, are in dire need of new treatment options,” trial investigator James F. Howard Jr., MD, a professor of neurology, medicine, and allied health at the University of North Carolina School of Medicine, said in a statement.1 “These updated results continue to show deep responses durable for months after cessation of treatment in both heavily pretreated participants and, notably, participants without prior exposure to biologic drugs, underscoring the potential for Descartes-08 to emerge as a meaningful addition to available MG treatments.”
Alongside the updated data, Cartesian announced that it plans to launch a phase 3 clinical trial, dubbed AURORA (NCT identifier pending), for Descartes-08 in acetylcholine receptor autoantibody positive MG in the first half of next year. In the randomized, placebo-controlled trial, an estimated 100 patients will receive Descartes-08 in 6 weekly outpatient doses. The proportion of patients treated with the CAR-T who achieve an improvement of at least 3 points on the MG-ADL compared to the placebo group at 4 months posttreatment will constitute the primary end point. Safety data and data from other MG severity scales will make up secondary end points.
“Data reported today add to the growing body of evidence supporting the potential for Descartes-08 to provide deep and durable improvements for participants with MG in the convenient outpatient setting and without the need for preconditioning chemotherapy,” Carsten Brunn, PhD, the president and chief executive officer of Cartesian, added to the statement.1 “Importantly, we believe these updated results align well with the end points of our planned phase 3 trial, strengthening our confidence in the design of the next phase of Descartes-08’s development. We look forward to commencing the trial during the first half of next year as we continue to work toward our mission to deliver this much-needed therapy to patients with MG.”
CGTLive® previously spoke with Miloš Miljković, MD, the chief medical officer of Cartesian Therapeutics, at the American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting, held May 7 to 10, 2024, in Baltimore, Maryland, to learn more about Descartes-08 and its potential in treating MG.2 He discussed follow-up of patients in the phase 2a portion of the clinical trial and shared future plans for Descartes-08 in MG and other autoimmune indications.
“We're also looking at other indications in the autoimmune space,” Miljković told CGTLive®. “When you have a treatment that has no lymphodepletion and it's an outpatient setting you can really have a broad choice of possible indications, so we're really taking a careful look at that.”
