1st patient enrolled in Phase 3 trial of MG cell therapy Descartes-08
AURORA study is expected to enroll 100 adults with generalized MG
The first patient has joined a Phase 3 clinical trial assessing the safety and efficacy of Descartes-08, an investigational cell therapy for myasthenia gravis (MG) being developed by Cartesian Therapeutics.
Called AURORA (NCT06799247), the trial is expected to enroll 100 adults with generalized MG (gMG), a more severe form of MG that features widespread muscle weakness. It’s currently recruiting participants at a site in California.
“With the first participant now successfully enrolled, commencement of our Phase 3 AURORA trial represents a significant milestone in our mission to deliver a differentiated, durable treatment option to patients with MG,” Carsten Brunn, PhD, Cartesian’s president and CEO, said in a company press release.
MG is caused by self-reactive antibodies that commonly target acetylcholine receptors (AChRs) at the neuromuscular junction, which is where nerve and muscle cells communicate to control voluntary movements. The antibodies disrupt the communication between nerve and muscle cells, leading to the disease’s symptoms. Antibodies are immune proteins made by B-cells, specialized immune cells. Descartes-08 is a CAR T-cell therapy that’s designed to reduce the number of B-cells and lower levels of MG-driving antibodies.
The treatment involves collecting a patient’s T-cells, another immune cell type that’s capable of killing other cells, and engineering them to carry a chimeric antigen receptor (CAR) that targets B-cell maturation antigen, a protein on B-cells. The modified T-cells that have been instructed to recognize and kill B-cells are then infused back into the patient.
Unlike other CAR-T cell therapies where patients undergo preconditioning — a chemotherapy regimen to destroy existing immune cells — before receiving the engineered T-cells, Descartes-08 can be infused without needing hospitalization or chemotherapy.
Testing Descartes-08 in MG
Results from MG-001 (NCT04146051), a Phase 2b trial testing Descartes-08 in adults with gMG, showed that six weekly infusions led to sustained reductions in disease severity over a placebo. This positive effect was maintained through one year.
“With sustained benefits observed through 12 months in our Phase 2b trial, we believe Descartes-08 has the potential to transform the current MG treatment paradigm with just a single course of therapy,” Brunn said.
Descartes-08 was also well tolerated, with no reported cases of severe immune responses such as are often seen with conventional CAR T-cell therapies.
“Supported by compelling results from the Phase 2b trial, I firmly believe that Descartes-08 has the potential to serve as a safe, flexible, and durable treatment option for patients with MG,” said James F. Howard Jr., MD, clinical advisor for Cartesian and professor at the University of North Carolina School of Medicine.
The AURORA trial will assess the safety and efficacy of Descartes-08 in adults with gMG who are positive for anti-AChR antibodies. The participants will receive Descartes-08, or a placebo, weekly for six weeks. The U.S. Food and Drug Administration agreed on the trial design this year.
The main goal is to assess the proportion of patients who achieve a clinically meaningful improvement in the MG Activities of Daily Living (MG-ADL) scale, meaning a score reduction of at least 3 points, after four months. The MG-ADL is a standard measure of disease severity that assesses its impact on daily life.
The company also plans this year to initiate a Phase 2 basket trial of Descartes-08 in children with juvenile MG and other autoimmune diseases.
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