Descartes-08 shown to reduce gMG disease severity up to 1 year in trial
New data show sustained benefits of cell therapy for 5 of 7 patients in study
Treatment with the experimental cell therapy Descartes-08 led to reductions in disease severity that were sustained out to one year for five of seven generalized myasthenia gravis (gMG) patients taking part in a Phase 2a clinical trial.
That’s according to new data, announced by the therapy’s developer Cartesian Therapeutics, that focused on seven people treated in the second part of an ongoing trial.
“The 12-month data build on the positive data reported [in 2023] in The Lancet Neurology, underscoring the potential of Descartes-08 to drive deep and durable responses in patients with MG,” Milos Miljkovic, MD, Cartesian’s chief medical officer, said in a company press release.
According to Cartesian, the therapy was well-tolerated by all of the patients, with no dose-limiting toxicities observed.
New data focused on 7 patients in ongoing study’s 2nd part
Descartes-08 works by taking T-cells from a patient and engineering them in a lab to equip them with a human-made protein called a chimeric antigen receptor (CAR). It directs the T-cells to attack BCMA, a protein that’s expressed by B-cells. The engineered cells are then infused back into the patient with the aim of destroying B-cells.
B-cells are the immune cells chiefly responsible for making antibodies: MG is caused by self-targeting antibodies that interfere with the communication between nerve and muscle cells.
By depleting B-cells, Descartes-08 aims to reduce levels of these disease-driving antibodies to ultimately relieve disease symptoms.
Most CAR T-cell therapies use DNA to introduce the receptor to T-cells. This approach requires giving a patient chemotherapy to deplete existing immune cells before the therapeutic cells are infused — a process called conditioning. Descartes-08 instead uses RNA, an intermediate molecule generated during the translation of DNA into a protein, with the aim of allowing the therapy to be given without such a conditioning regimen.
In the first, open-label Phase 1b/2a portion of the MG-001 clinical trial (NCT04146051), 14 people with gMG were treated with Descartes-08. The therapy was able to be given without requiring hospitalization or chemotherapy, and no major safety issues were reported. That included no instances of neurotoxicity or cytokine release syndrome, both potentially serious inflammatory reactions frequently seen with CAR T-cell therapies.
The new data focused on the seven patients in the Phase 2a part of the trial, all of whom received once-weekly infusions of Descartes-08 for six weeks.
According to Cartesian, all seven patients showed “marked and long-lasting clinical improvements” after nine months in the study. Such improvements were seen on four standardized measures of MG severity: the MG Composite, the MG Activities of Daily Living, the Quantitative MG scores, and the Quality of Life 15-revised.
Phase 2b part of study now enrolling adults with gMG
By study month 12 — approximately 10 months after the last infusion of Descartes-08 was given — five of the patients maintained clinical improvement in these four measures, according to Cartesian.
“Most patients maintained robust, clinically meaningful improvements across all four standard MG severity scores approximately 10 months after the last infusion,” Miljkovic said.
The other two patients experienced a loss of clinical efficacy by study month 12. One of these patients was retreated with another round of Descartes-08 therapy, and this led to “rapid improvement in clinical scores,” the company stated. At six months of follow-up after the second round of therapy, this patient still had minimal MG symptoms.
The lasting reductions in autoantibody [levels] are consistent with the observed clinical responses and the proposed mechanism of action for Descartes-08, supporting the deep and long-lasting effects observed in the study.
At the start of the study, three of the seven patients had detectable antibodies targeting acetylcholine receptor (AChR), the most common type of MG-driving antibody. In these three patients, anti-AChR antibody levels were reduced at six months. Antibody levels lowered even further at nine months, and stayed low out to 12 months.
“The lasting reductions in autoantibody titers are consistent with the observed clinical responses and the proposed mechanism of action for Descartes-08, supporting the deep and long-lasting effects observed in the study,” Miljkovic said.
Cartesian now is enrolling patients in the Phase 2b portion of the study, which is expected to include up to 30 adults with gMG. The Phase 2b part will use a placebo-controlled crossover design, in which patients initially receive six once-weekly infusions of either Descartes-08 or a placebo. Following that part, the patients given active therapy will get six weekly placebo infusions and those initially given the placebo will receive the active therapy.
Recruitment is ongoing at sites in the U.S. and Canada, with top-line results expected later this year.
Cartesian also is planning in the coming months to launch a separate clinical trial (NCT06038474) that will test Descartes-08 in people with systemic lupus erythematosus, known as SLE, which like MG is an autoimmune disease driven by self-targeting antibodies.