MDA 2026: CAR T-cell therapy Descartes-08 eases MG symptoms
Cell therapy outperforms placebo in gMG patients positive for AChR antibodies
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- Descartes-08, a CAR T-cell therapy, significantly eased gMG symptoms.
- The treatment was effective in gMG patients with anti-AChR antibodies.
- A Phase 3 trial is currently recruiting patients.
Cartesian Therapeutics’ experimental cell therapy Descartes-08 outperformed a placebo at easing symptoms of generalized myasthenia gravis (gMG) in patients who test positive for self-reactive antibodies targeting the acetylcholine receptor (AChR) protein.
That’s according to a new subgroup analysis of the Phase 2b MG-001 clinical trial (NCT04146051). Previous trial data showed the therapy was effective in the broader study population, which included gMG patients with or without anti-AChR antibodies, the most common type of gMG-driving antibody.
Tahseen Mozaffar, MD, a professor at the University of California, Irvine, shared the findings in an oral presentation at the 2026 Muscular Dystrophy Association Clinical & Scientific Conference, held March 8-11 in Orlando, Florida, and virtually. The presentation was titled “Efficacy and [Safety] of Descartes-08 in AChR+ generalized myasthenia gravis: subgroup analysis of a phase 2b randomized, placebo-controlled trial.”
Descartes-08 led to a “definite improvement that was more above and beyond what is expected from … a meaningful clinical improvement,” Mozaffar said. “And then they were minimal treatment-related effects.”
Cartesian is running a Phase 3 clinical trial, AURORA (NCT06799247), which aims to compare the safety and efficacy of Descartes-08 against a placebo in up to 100 adult gMG patients with anti-AChR antibodies. The study began enrolling patients last year, and it is currently recruiting at sites in the U.S., Italy, Turkey, Poland, Serbia, and Spain.
Treatment doesn’t require hospitalization
gMG is caused by self-reactive antibodies that block signaling from nerve cells to muscle cells, leading to MG symptoms such as muscle weakness and fatigue. The most common type of gMG-causing antibody targets AChR, a muscle protein that normally helps detect signals from nerve cells.
Descartes-08 is a CAR T-cell therapy designed to deplete B-cells, the immune cells responsible for making gMG-driving antibodies.
The therapy initially involves collecting T-cells, a type of immune cell that can kill other cells, from a patient. The T-cells are then modified in the lab to carry a chimeric antigen receptor (CAR) protein that targets BCMA, a protein found at the surface of B-cells. This CAR works like a human-made molecular weapon, directing T-cells to attack B-cells. The engineered cells are then infused back into the patient.
With many CAR T-cell therapies, patients undergo preconditioning, a procedure before treatment in which intensive medications, such as chemotherapy, are used to wipe out existing immune cells and make way for the therapeutic cells.
Descartes-08 has no preconditioning requirement, allowing therapy infusions to be given in an outpatient setting (i.e., without hospitalization).
The MG-001 study enrolled 36 gMG patients who tested negative for antibodies against the muscle-specific tyrosine kinase (MuSK) protein, the second-most common disease-driving antibody. Participants received weekly infusions of either Descartes-08 or a placebo for six weeks and were followed for up to one year.
The study’s main goal was to determine whether more patients given Descartes-08 would achieve a 5-point or greater reduction in a measure of disease severity, the Myasthenia Gravis Composite (MGC) score, than those in the placebo group. A reduction of 3 points on the MCG score is considered clinically meaningful.
Previously announced results showed that the trial met its main goal, with significantly more Descartes-08-treated patients achieving an MCG response at three months relative to those given the placebo (66.7% vs. 27.3%). Group differences were maintained for up to one year.
New data show ‘fairly prominent and significant response’
Newly presented data concerned the subgroup of 19 evaluable participants who were positive for anti-AChR antibodies. Of the 11 patients treated with Descartes-08, seven (63%) achieved a 5-point drop in MCG score within three months. By contrast, only one of the eight patients given the placebo (12.5%) met that outcome. This difference was statistically significant.
“There was a fairly prominent and significant response in the greater than 5-point improvement in MG Composite score compared to placebo,” Mozaffar said.
Mozaffar noted that more stringent cutoffs showed even greater differences. About a third of patients given Descartes-08 (36.4%) showed an MCG score reduction of at least 6 points, and more than a third (27.3%) experienced a score drop of 7 or more points, while no participants in the placebo group experienced such improvements.
Other measures of disease severity, the MG Activity of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores, showed similar differences. Average MG-ADL and QMG scores both improved by more than 3 points in patients given Descartes-08, and by less than a point in those given a placebo.
Average MG-ADL and QMG scores dropped by more than 3 points in Descartes-08-treated patients (surpassing clinically meaningful reductions), and by less than a point in those given the placebo. Meaningful reductions in both scores were maintained out to a year of follow-up.
As previously reported, the most common side effects in patients given Descartes-08 were infusion reactions such as chills (62.5%), fever (50%), headache (43.8%), and nausea (43.8%). These usually resolved after two days. No adverse events were reported from month 3 onward.
“Outpatient Descartes-08 administration was associated with clinically meaningful improvements in [disease severity] scores in patients positive for [anti-AChR antibodies] with no concerning safety signals,” the researchers wrote in their abstract.
Note: The Myasthenia Gravis News team is providing live coverage of the 2026 MDA Clinical & Scientific Conference March 8-11 in Orlando, Florida. Go here to see the latest stories from the conference.
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