MGFA Session 2026: Repeat CAR T-cell care eases gMG for some
Second round could give sustained, clinically meaningful symptom reduction
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- A second round of Descartes-08 CAR T-cell therapy provides sustained, meaningful symptom reduction for some gMG patients experiencing disease recurrence.
- Clinical trial data showed a rapid response that was sustained for one year.
- Developer Cartesian Therapeutics expects to file for FDA approval of Descartes-08 next year.
A second round of Descartes-08, Cartesian Therapeutics’ experimental CAR T-cell therapy, may allow some people with generalized myasthenia gravis (gMG) to sustain clinically meaningful symptom reduction, according to data from a clinical trial.
James F. Howard Jr., MD, a trial investigator and University of North Carolina School of Medicine neurologist, presented the findings at the American Association of Neuromuscular & Electrodiagnostic Medicine annual meeting. They were also announced by Cartesian Therapeutics in a press release.
Howard’s talk, part of the Myasthenia Gravis Foundation of America scientific session, was titled “Durability of response following retreatment with Descarte-08, an autologous BCMA-directed mRNA CAR T-cell therapy, in generalized myasthenia gravis: a case series with 12-month follow-up.”
The trial results suggest that “patients who initially responded to Descartes-08 and who have [symptom] recurrence will do well with retreatment,” and this improvement “is sustained through 12 months post-treatment,” said Howard, who is also a clinical advisor to Cartesian.
Treatments have limitations
The ongoing Phase 3 AURORA clinical trial (NCT06799247) is confirming the therapy’s benefits in about 100 adults with gMG. Cartesian hopes that AURORA results will support a 2027 application for U.S. approval of Descartes-08.
In myasthenia gravis (MG), the immune system produces abnormal antibodies that mistakenly attack proteins important for communication between nerve cells and muscles. This causes muscle weakness, affecting muscle groups throughout the body for people with gMG.
While MG treatments are available, they have several limitations.
“There remains a significant unmet need for patients suffering from MG today where current treatment options require patients to utilize chronic immunosuppressants to manage the disease,” said Howard.
CAR T-cell therapy aims to provide more sustained effects with a limited dosing period. It typically involves collecting a patient’s own immune T-cells, which can kill other cells. The T-cells are then engineered to carry a chimeric antigen receptor (CAR) protein, which binds to a specific target.
In the case of Descartes-08, the CAR targets B-cell maturation antigen (BCMA), a protein found on the surface of B-cells, which produce antibodies, including those that drive MG. Patients then receive six weekly infusions of these engineered T-cells, which will kill BCMA-positive B-cells, ultimately reducing levels of MG-driving antibodies.
Unlike many other CAR T-cell therapies, Descartes-08 doesn’t require patients to undergo lymphodepletion, a type of intensive chemotherapy designed to kill immune cells, before the infusion.
The therapy showed early signs of potential success in adults with gMG in the Phase 1/2 MG-001 clinical trial (NCT04146051), with participants’ MG symptoms reduced and benefits lasting at least one year after treatment.
For some people, however, gMG symptoms eventually worsened again. Investigators tested whether a second round of Descartes-08 (five weekly infusions) could reduce disease severity in five people (mean age 58) with disease recurrence.
The second round started an average of 16.6 months after their first round ended. Investigators assessed changes in MG Activities of Daily Living (MG-ADL) and MG Composite (MGC) scores, which measure symptom severity.
Both scores dropped soon after starting the second treatment, indicating easing of symptoms, and these responses were sustained over time. After one year, MCG scores had fallen an average of 15 points and MG-ADL scores had dropped by 6.6 points, both clinically meaningful changes.
“There’s a relatively rapid response over the course of a couple of months, which then is maintained” for up to one year, in contrast with responses seen after the initial treatment in these patients, Howard said. Whether repeat dosing “improve[s] the durability of the response … remains to be seen.”
One woman in trial saw ‘sustained effect’
The neurologist highlighted the case of a patient of his, a 52-year-old woman, who received Descartes-08 in the trial after failing to respond to other treatments. She “had a very rapid improvement [with Descartes-08] and then lost it, [was] retreated, [and saw a] sustained effect,” he said.
Descartes-08 was generally safe and well tolerated. There were no reports of cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome, two potentially serious complications of CAR T-cell therapies. Participants didn’t show signs of low blood counts or low antibody levels.
All the recorded treatment-related adverse events “are essentially related to the infusion process itself,” Howard said. The number of infusion-related reactions was comparable during initial treatment and retreatment.
“For patients who have already cycled through multiple therapies, the option to retreat a CAR-T cell therapy, in an outpatient setting and without lymphodepleting chemotherapy, represents an exciting potential advancement in the field of MG,” Howard said.
While the results are preliminary, they support Descartes-08’s safety and efficacy, according to Howard and Carsten Brunn, PhD, Cartesian’s CEO.
“We believe the combination of sustained symptom improvement, the ability to retreat if symptoms return, and the quality-of-life benefits of outpatient administration without lymphodepleting chemotherapy sets Descartes-08 apart and has the potential to meaningfully change the way MG is treated,” Brunn said. “These data strengthen our conviction in Descartes-08 as we approach topline results from our Phase 3 AURORA trial, expected in the first quarter of 2027.”
Note: The Myasthenia Gravis News team is providing virtual coverage of the Myasthenia Gravis Foundation of America’s scientific session at the American Association of Neuromuscular & Electrodiagnostic Medicine Annual Meeting on Sept. 29. Go here to see the latest stories from the conference.
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