FDA agrees on design of Phase 3 trial to test Descartes-08 in MG
Cartesian says it plans to launch AURORA trial in 2025 first half
Cartesian Therapeutics has aligned with the U.S. Food and Drug Administration (FDA) on the design of the planned Phase 3 AURORA trial that will test its investigational cell therapy Descartes-08 in people with myasthenia gravis (MG).
The FDA, under its special protocol assessment process, provided written agreement that the proposed trial design would be sufficient to support an eventual regulatory application seeking the approval of the treatment in MG, subject to final trial results, the company said.
AURORA, on track to launch this year, will evaluate Descartes-08’s ability to ease disease severity relative to a placebo among around 100 MG patients positive for antibodies against acetylcholine receptors (AChRs), the most common type of MG-causing antibodies.
The agreement “marks an important milestone in the development of Descartes-08 for MG, providing critical regulatory clarity and a clear path toward potential approval,” Carsten Brunn, PhD, president and CEO of Cartesian, said in a company press release. “We look forward to commencing the Phase 3 AURORA trial in the first half of this year.”
Descartes-08 is a CAR T-cell therapy designed to help the immune system target and kill off B-cells, which are responsible for the production of the self-reactive antibodies that impair nerve-muscle communication in MG.
Using mRNA
T-cells are a type of immune cell naturally capable of recognizing and eliminating potentially harmful cells. CAR T-cell therapy involves engineering T-cells to recognize and attack a designated target.
With Descartes-08, a person’s T-cells are collected and engineered in the lab to carry a chimeric antigen receptor, or CAR, designed to specifically recognize a protein on B-cells called B-cell maturation antigen. Once infused back into the patient, the modified T-cells are expected to launch an attack against B-cells.
Descartes-08 differs from traditional CAR T-cell approaches in that, instead of using DNA to introduce the CAR into T-cells, it uses messenger RNA (mRNA), an intermediate molecule used by cells as a template to make proteins.
Unlike conventional CAR T-cell therapies, Descartes-08 does not require patients to undergo chemotherapy to wipe out existing immune cells before receiving treatment. As a result, it may help avoid some of the side effects seen with traditional CAR T-cell therapies. Cartesian also expects that Descartes-08 can be safely administered in an outpatient setting.
Support for the AURORA launch came in the form of positive data from the ongoing Phase 1/2 MG-001 trial (NCT04146051) designed to test Descartes-08 in people with generalized MG.
In the study’s Phase 2b portion, 36 patients were randomly assigned to receive weekly infusions of Descartes-08 or a placebo for six weeks, and were then monitored for several months.
Data showed that a significantly higher proportion of people given the CAR T-cell therapy achieved clinically meaningful reductions in disease severity after three months relative to a placebo, with similar benefits seen in the subgroup of patients who were positive for anti-AChR antibodies.
Additional analyses showed that clinical responses to the therapy further deepened over time, and were sustained through a year for patients with evaluable data.
The treatment was well tolerated. Certain severe immune responses that are typical of traditional CAR T-cell therapies were not seen with Descartes-08.
Findings from the study’s Phase 2a portion similarly indicated that the therapy led to lasting clinical improvements.
“Supported by compelling Phase 2b results where we observed deep and durable improvements in patients with MG, we firmly believe that Descartes-08 has the potential to serve as a meaningful new therapy that can be delivered in the convenient outpatient setting without the need for preconditioning chemotherapy,” Brunn said.
In AURORA, participants will be randomly assigned to receive six once-weekly infusions of Descartes-08 or a placebo. The main goal is to evaluate the proportion of participants who achieve at least a 3-point improvement in the score of the MG Activities of Daily Living (MG-ADL), a standard measure of MG severity, after four months.
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