MGFA Session 2026: CAR T-cell therapy shows promise in early gMG trial
Data show experimental treatment rese-cel may safely ease symptoms in adults
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- The experimental CAR T-cell therapy rese-cel may safely ease symptoms in adults with generalized myasthenia gravis.
- That's according to an early clinical trial where participants experienced benefits with a single infusion.
- Rese-cel targets CD19, a protein present at the surface of B-cells that produce disease-causing antibodies.
A small clinical trial found early signs that Cabaletta Bio’s experimental CAR T-cell therapy rese-cel (resecabtagene autoleucel) may safely ease symptoms for adults with generalized myasthenia gravis (gMG).
That’s according to data from the U.S.-based Phase 1/2 RESET-MG trial (NCT06359041), in which participants with different types of disease-causing antibodies experienced benefits with a single infusion of rese-cel, formerly known as CABA-201.
The findings were shared by Ali Habib, MD, a trial researcher and a neurologist at the University of California, Irvine, in an oral presentation at the Myasthenia Gravis Foundation of America scientific session during the American Association of Neuromuscular & Electrodiagnostic Medicine annual meeting, held Sept. 29 to Oct. 2 in Orlando, Florida.
The talk was titled “RESET-MG: Clinical Trial Evaluating Rese-cel (Resecabtagene Autoleucel), A Fully Human, Autologous 4-1BB CD19-CAR T Cell Therapy in Generalized Myasthenia Gravis.”
“We’ve gone from effective therapy that was slow to work and had a lot of side effects to therapies that give us rapid onset, better safety profile, long term durability, but requir[e] repeat dosing,” Habib said. CAR T-cell therapy “is looking at doing all of those things and the next step up: giving durability without the need for retreatment, potentially.”
Rese-cel targets key protein
Myasthenia gravis (MG) is an autoimmune disease that causes muscle weakness and other symptoms. In gMG, this affects muscles throughout the body.
Typically, the self-reactive antibodies that drive MG target the acetylcholine receptor (AChR) protein, which helps muscle cells and nerve cells communicate. However, some people with MG have antibodies that target other proteins, or no clear disease-causing antibodies.
CAR T-cell therapies currently in development for MG, including rese-cel, aim to reduce production of these self-reactive antibodies. They use chimeric antigen receptor (CAR) proteins to help a patient’s immune T-cells identify and attack B-cells, the immune cells that produce antibodies.
Rese-cel involves collecting a patient’s T-cells and engineering them to carry a CAR directed against CD19, a protein present at the surface of B-cells. After a single into-the-vein infusion of the engineered CAR T-cells, the immune system can target and deplete B-cells, reducing abnormal antibody production.
Cabaletta is sponsoring RESET-MG to evaluate the safety and preliminary efficacy of rese-cel in adults with gMG for up to nearly three years.
Newly presented results concern 14 participants who underwent lymphodepletion, a type of chemotherapy designed to kill existing immune cell populations and make room for the delivered immune cells, before rese-cel.
Eight of the participants tested positive for anti-AChR (AChR group), while the remaining six had other types of MG-driving antibodies or no known disease-causing antibodies (no-AChR group).
“Most of the patients … [have] received multiple other therapies and have not had an adequate response to these therapies,” Habib said.
Therapy ‘did well in terms of the safety and tolerability’
Before receiving rese-cel, participants also stopped taking immunosuppressive medications, with the exception of corticosteroids, the abrupt discontinuation of which can cause serious complications.
As of September, participants had been followed for a mean of 38 weeks (more than 8.5 months), and up to more than one year.
Data showed that rese-cel “did well in terms of the safety and tolerability,” which is the trial’s main goal, Habib said.
Two participants experienced mild or moderate cytokine release syndrome, a potentially serious immune response to CAR T-cell therapies. The cases resolved, one with appropriate treatment. No other potential CAR T-cell therapy complications were reported.
Two people experienced treatment-related serious adverse events. One involved decreased appetite and a body function decline due to extended bed rest or inactivity, and the other experienced fever with low levels of neutrophils, a type of immune cell.
One patient died about a year after the infusion, but this death was deemed unrelated to rese-cel.
Participants’ CAR T-cell levels peaked two weeks after treatment, mirrored by a drop in B-cell levels. About three months post-infusion, B-cell populations began to recover.
“These are the very early stage B-cells that are first entering circulation from the bone marrow very early in their maturation stage,” Habib said. This finding suggests a potential immune reset, which might sustainably decrease disease-causing antibody production.
Score measuring disease impact saw meaningful reduction
A total of 10 participants completed six months of follow-up without requiring rescue treatment for an MG exacerbation.
Results from these patients showed clinically meaningful score reductions (improvements) in MG Activities of Daily Living (MG-ADL), which assesses the disease’s impact on daily life, and Quantitative MG (QMG), which measures muscle weakness.
Specifically, the MG-ADL score dropped by a mean of 7.8 points in the AChR group and 8 points in the non-AChR group, and the QMG score decreased by a mean of 8.8 points in the AChR group and 6.8 points in the non-AChR group. Benefits were seen as soon as four weeks after the infusion.
In addition, all but one of the 10 patients who responded to rese-cel were able to stop corticosteroids.
Next trial steps include testing rese-cel without the lymphodepletion regimen. Enrollment for this group of patients is open, Habib noted.
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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