Myasthenia Gravis Awareness Month 2025: CAR-T Continues Steady Progress
In observance of Myasthenia Gravis Awareness Month, held annually in June, we took a look back at the past year's progress in bringing CAR-T to this autoimmune disease.
Myasthenia gravis (MG) is a rare neuromuscular disorder, characterized by weakening of the skeletal muscles that drive movement, that affects at least 36,000 to 60,000 people in the United States. MG is among the autoimmune diseases that has recently attracted attention for the development of chimeric antigen receptor T-cell (CAR-T) therapy, and several biotech companies are currently working on such products for the indication.
In honor of Myasthenia Gravis Awareness Month, observed annually in June by the patient and clinician communities, CGTLive® is taking a look back at the steady progress that has been ongoing for CAR-T candidates in MG over the past year. Click the "READ MORE" buttons for more details and information about each item.
Cartesian Therapeutics’ mRNA CAR-T Descartes-08 Shows Efficacy and Safety in Myasthenia Gravis in Phase 2 Study
April 23, 2025 — Cartesian Therapeutics’ Descartes-08, an investigational autologous mRNA-engineered CAR-T therapy that targets B-cell maturation antigen (BCMA), has demonstrated therapeutic effects in a phase 2b double-blind, placebo-controlled, crossover trial (NCT04146051) in MG. Sustained responses over a 12-month period were seen in treated patients, along with a safety profile that was aligned with previously reported data.
In the trial, heavily pretreated, highly symptomatic patients with MG (n = 36) were randomly assigned in a 1:1 fashion to undergo a 12-month treatment phase with either Descartes-08 or a placebo. Treatment with the CAR-T therapy, in the 12 patients who had available data, led to reductions of 5.5 (±1.1) and 4.8 (±1.4) in Myasthenia Gravis-Activities of Daily Living (MG-ADL) scores at 4 months and 12 months posttreatment, respectively. Furthermore, an average Quantitative Myasthenia Gravis Score (QMG) reduction of 4.8 (±1.7) points at 4 months posttreatment, which deepened through 12 months posttreatment (6.0 [±2.1]), was seen in these patients.
"This impressive data highlights the potential of Descartes-08 to serve as an important therapeutic option to deliver deep and sustained reductions in MG-ADL for patients with MG," trial investigator Tuan Vu, MD, a professor of neurology at the University of South Florida Morsani College of Medicine, and the director for Neuromuscular Medicine and EMG, said in a statement. "The data in participants who had not received prior biologic therapy is particularly striking as this population is most comparable to the patient populations in trials of standard-of-care biologics."
Cabaletta Bio’s CAR-T CABA-201 Cleared by FDA for Trial in Generalized MG
November 27, 2024 — Cabaletta Bio’s CABA-201, an investigational CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy intended to treat various indications, has received clearance from the FDA for a phase 1/2 clinical trial (RESET-MG; NCT06359041) in generalized MG.
During the same month, the company reported that CABA-201 effected responses or possible emerging responses in some patients treated in the phase 1/2 RESET-SLE clinical trial (NCT06121297) for systemic lupus erythematosus (SLE) and lupus nephritis (LN), the phase 1/2 RESET-Myositis clinical trial (NCT06154252) for active idiopathic inflammatory myopathy (IIM), and the phase 1/2 RESET-SSc clinical trial (NCT06328777) in systemic sclerosis (SSc). These data were presented at the 2024 American College of Rheumatology (ACR) Convergence, held November 14 to 19 in Washington, DC.
Kyverna’s CAR-T Gets RMAT Designation for Myasthenia Gravis
August 13, 2024 — The FDA has granted Regenerative Medicine Advanced Therapy (RMAT) to Kyverna Therapeutics’ KYV-101 CAR T-cell therapy for the potential treatment of progressive MG.
"The RMAT designation underscores the attention and interest by the FDA in the development of potentially transforming therapies targeting a severe autoimmune disease such as MG," principal investigator Srikanth Muppidi, MD, a neuromuscular disorder specialist at Stanford Medicine in Palo Alto, California, said in a statement. "We are witnessing an era of profound changes in the approach to autoimmune conditions and ultimately, we hope this leads to a symptom-free state for patients."
KYV-101 is an autologous, fully human CD19-targeted CAR T-cell therapy. Kyverna has been expanding the use of KYV-101 into a number of B cell-driven autoimmune diseases after the CAR in KYV-101 was originally designed by the National Institutes of Health (NIH) for use in oncology.
IASO Reports Positive First Uses of Eque-Cel for CNS Autoimmunity
July 3, 2024 — IASO Bio has steadily been exploring the use of its investigational autologous BCMA-directed CAR-T therapy equecabtagene autoleucel (eque-cel) in autoimmune indications, with promising reports of use in patients with neuromyelitis optica spectrum disorder (NMOSD), MG, and immune-mediated necrotizing myopathy (IMNM).
The recent case reports are part of a clinical phase 1 program (NCT04561557) investigating eque-cel in nervous system autoimmunity indications, under principal investigator Professor Wei Wang from Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.
The company recently published data on 2 participants with MG, a 33-year old female and a 60-year old female, who received 1.01×106 CAR-T/Kg and 0.96×106 CAR-T/Kg, respectively. After receiving eque-cel, 1 developed grade 1 cytokine release syndrome. There were no cases of immune effector cell-associated neurotoxicity syndrome. Serious cases of hemocytopenia recovered within 4 weeks of infusion. Starting at 3 months after infusion, the patients showed significant improvement in limb strength and vital capacity, and sustained improvement in Myasthenia Gravis-Activities of Daily Living Score (MG-ADL), Quantitative Myasthenia Gravis Score (QMG), Myasthenia Gravis-Quality of Life Score (MG-QOL), and Modified Rankin Score (mRS). The patients received only low dose pyridostigmine during the follow-up period as immunomodulatory therapy.
