Cartesian Therapeutics’ mRNA CAR-T Descartes-08 Continues to Show Efficacy in Phase 2b Myasthenia Gravis Trial

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Cartesian also announced that the first patient has been dosed in a separate clinical trial evaluating the CAR-T therapy in systematic lupus erythematosus.

Tahseen Mozaffar, MD, a professor of neurology, pathology and laboratory medicine, director of the Division of Neuromuscular Diseases, and director of the ALS and Neuromuscular Center at the University of California, Irvine

Tahseen Mozaffar, MD
Credit: University of California, Irvine

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 demonstrated the ability to bring about clinically improvements in MG Composite (MGC) score for patients treated with the CAR-T compared to patients who received a placebo treatment.1

The data comes from the phase 2b portion of a clinical trial (NCT04146051) evaluating Descartes-08 for MG that is using MGC as a primary end point.1 At 3 months posttreatment, 10 of 14 patients (71%) in the modified intent-to-treat (mITT) group, all of whom received at least 1 dose of Descartes-08, achieved a 5-point or greater improvement in MGC score. In comparison, only 3 of 12 patients (25%) who received the placebo in the mITT showed a 5-point or greater improvement in MGC score (P = .018). Furthermore, in the trial’s per-protocol population, which included 16 patients who received Descartes-08 and 15 patients who received the placebo, 11 patients (69%) treated with Descartes-08 showed a 5-point or greater improvement in MGC score at 3 months of follow-up compared to 5 patients (33%) treated with the placebo who achieved the same (P = .048).

Cartesian Therapeutics noted that the findings were consistent with results previously seen in the trial’s phase 2a portion. Furthermore, patients who responded to Descartes-08 showed improvements across the MG severity scales at 3 months posttreatment averaging at -5.6 for MG-Activities of Daily Living; -8.3 for MGC; -5.0 for Quantitative MG; and –7.9 for MG Quality of Life Revised Scale. The company also pointed out that for the 5 responding patients who reached 4 months of follow-up and the 3 responding patients who reached 6 months of follow-up, improvements were maintained or continued to improve more.

In terms of safety, Cartesian characterized the CAR-T product as “favorable” and “well-tolerated” in the phase 2b study, with adverse events that were “transient and mostly mild”.1 None of the treated patients experienced cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. Notably, Descartes-08 is administered in an outpatient setting without the use of lymphodepletion.

“MG is a devastating, rare autoimmune disorder with high unmet need for short-course treatments,” Tahseen Mozaffar, MD, a professor of neurology, pathology and laboratory medicine, director of the Division of Neuromuscular Diseases, and director of the ALS and Neuromuscular Center at the University of California, Irvine, said in a statement.1 “The current standard of care, chronic use of steroids and other immunosuppressants, is often associated with broad immunosuppression and limited efficacy. The durable improvements observed across all disease severity scales, the average of which was approximately 3 times greater than what is considered clinically meaningful, firmly support the potential for Descartes-08 to serve as an important new therapy for patients with MG that can be administered safely in the outpatient setting. I look forward to participating in its continued development.”

Cartesian also reported updated results from 2 patients who were retreated with Descartes-08 after previously receiving initial treatment in the phase 2a portion of the trial. According to the company, the retreated patients showed rapid improvement in clinical scores and have maintained a state of minimal symptom expression for up to 1 year after being treated with the second cycle of Descartes-08, with a similar time course and response magnitude to that reported following their first treatment with the product.

In addition to MG, Descartes-08 is also being evaluated for the treatment of systematic lupus erythematosus (SLE) in a separate phase 2 clinical trial (NCT06038474).2 On July 2, 2024, Cartesian announced that the first patient has been dosed in this trial, which is ultimately expected to include up to 30 adults with SLE.

“Despite recent advances in the SLE treatment landscape, many patients receiving currently available therapies continue to experience severe, incapacitating symptoms and disease progression,” Carsten Brunn, PhD, the president and CEO of Cartesian, said in a statement.2 “Descartes-08 is purposefully designed to overcome the limitations associated with the application of conventional, costly DNA-engineered CART-cell therapies for autoimmune diseases. We believe that Descartes-08 could serve as a safe and effective outpatient option for the patients with SLE for whom existing therapies fall short. We are committed to unlocking the full potential of Descartes-08 and look forward to advancing this trial in the months ahead.”

Descartes-08 recently received regenerative medicine advanced therapy designation from the FDA for MG in May 2024.3 The therapy is comprised of patients’ own T-cells that have been modified ex-vivo with RNA to target B-Cell Maturation Antigen.4 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.

REFERENCES
1. Cartesian Therapeutics announces positive topline results from phase 2b trial of Descartes-08 in patients with myasthenia gravis. News release. Cartesian Therapeutics, Inc. July 2, 2024. Accessed July 2, 2024. https://ir.cartesiantherapeutics.com/news-releases/news-release-details/cartesian-therapeutics-announces-positive-topline-results-phase
2. Cartesian Therapeutics announces first patient dosed in phase 2 trial of Descartes-08 in systematic lupus erythematosus. News release. Cartesian Therapeutics, Inc. July 2, 2024. Accessed July 2, 2024. https://ir.cartesiantherapeutics.com/news-releases/news-release-details/cartesian-therapeutics-announces-first-patient-dosed-phase-2
3. Cartesian Therapeutics receives FDA regenerative medicine advanced therapy designation for Descartes-08 for the treatment of myasthenia gravis. News release. Cartesian Therapeutics, Inc. May 22, 2024. Accessed July 2, 2024. https://ir.cartesiantherapeutics.com/news-releases/news-release-details/cartesian-therapeutics-receives-fda-regenerative-medicine
4. 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 July 2, 2024. https://www.cartesiantherapeutics.com/2023/01/31/cartesian-therapeutics-announces-dosing-of-first-participant-in-a-phase-2b-randomized-clinical-trial/
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