Myasthenia Gravis Awareness Month 2024: Looking Back at a Year of Progress for CAR-T


In observance of Myasthenia Gravis Awareness Month, held annually in June, we took a look back at a year of 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. Over the past year or so, an explosion of interest has taken place across industry and academia in bringing chimeric antigen receptor T-cell (CAR-T) therapy to the field of autoimmune disease, and MG is among the indications that multiple companies have chosen to target with this initial wave of clinical trials.

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 unprecedented progress that has been made 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’ Myasthenia Gravis mRNA CAR-T Descartes-08 Garners FDA RMAT Designation

May 26, 2024 — Cartesian Therapeutics’ Descartes-08, an investigational autologous mRNA-engineered CAR-T therapy intended for the treatment of autoimmune diseases including MG, has received regenerative medicine advanced therapy (RMAT) designation from the FDA for MG.

Descartes-08 is comprised of patients’ own T-cells that have been modified ex-vivo with RNA to target B-Cell Maturation Antigen (BCMA). The use of RNA engineering is intended to avoid risks of genomic integration associated with DNA-based CAR-T therapies and to allow for control of pharmacokinetics.

The CAR-T product is currently being evaluated in the phase 2b portion of a clinical trial (NCT04146051) for MG. The first patient in this portion was dosed in January 2023.

IASO Bio’s CAR-T Eque-Cel Cleared for US Trial in Generalized Myasthenia Gravis

April 7, 2024 — IASO Biotechnology (IASO Bio)’s equecabtagene autoleucel (eque-cel, also known as CT103A), an investigational autologous BCMA-directed CAR-T therapy, has received clearance of an investigational new drug (IND) application from the FDA for a trial in generalized MG (gMG).

Eque-cel was previously evaluated in 2 patients with antibody-mediated idiopathic inflammatory disorders of the nervous system in the context of an investigator-initiated trial (NCT04561557). In these patients, clinical symptoms were reported to continue to improve over the 18 months following infusion of the CAR-T product. Furthermore, significant improvements in limb strength and vital capacity were observed at 3 months posttreatment, as were sustained improvements on instruments including the Myasthenia Gravis-Activities of Daily Living Score, Quantitative Myasthenia Gravis Score, Myasthenia Gravis-Quality of Life Score, and Modified Rankin Score.

In terms of safety, 1 of the patients experienced a grade 1 case of cytokine release syndrome (CRS). There were no other CRS cases or any cases of immune effector cell-associated neurotoxicity syndrome in the 2 patients. Within 4 weeks of receiving the CAR-T, all grade 3 or higher cases of hemocytopenia were recovered from.

Cabaletta Bio’s CAR-T CABA-201 Receives Fourth IND Clearance, With New Trial Set for Myasthenia Gravis

November 17, 2023 — Cabaletta Bio’s CABA-201, an investigational CD19-directed CAR-T therapy intended to treat autoimmune diseases, has received clearance from the FDA of its IND application for a clinical trial in gMG.

CABA-201 contains a 4-1BB costimulatory domain and is intended to deplete B-cells in order to “reset” the immune systems of patients. In light of the IND clearance, Cabaletta Bio intends to carry out a phase 1/2 clinical trial that will seek to enroll 12 patients in total. The participants will be divided into 2 equally sized cohorts, 1 of which will include patients with acetylcholine receptor (AChR) antibody-positive gMG and the other of which will include patients with AChR antibody-negative gMG. The IND clearance marks the fourth IND clearance for CABA-201. Earlier in 2023, the CAR-T previously was cleared by the FDA for separate trials in systemic lupus erythematosus and lupus nephritis (LN); active idiopathic inflammatory myopathy (also referred to as myositis); and systemic sclerosis.

“While we remain on track to deliver initial clinical data from CABA-201 treated patients with lupus and/or myositis in the first half of 2024, we are continuing to expand our CABA-201 portfolio beyond rheumatology and into neurology,” Steven Nichtberger, MD, the chief executive officer and co-founder of Cabaletta Bio, said in a statement. “The announcement of our fourth CABA-201 IND clearance is also our first IND clearance for the product candidate in a predominantly autoantibody mediated disease.”

Kyverna’s KYV-101 CAR T-Cell Therapy Expands Autoimmune Investigations Into Myasthenia Gravis

November 14, 2023 — The FDA has granted IND clearance for an open-label, phase 2 trial of Kyverna Therapeutics’ KYV-101 CAR T-cell therapy in 10 patients with MG.

"We have seen firsthand the transformative effects of KYV-101 in MG patients treated with the investigational therapy in our clinic," Prof. Dr. med. Aiden Haghikia, Director, Department of Neurology, Medical Faculty, Otto-von-Guericke University, said in a statement. "I welcome the FDA's decision and look forward to more clinical data to further our knowledge about CAR T-cell therapy in patients with severe neurological autoimmune diseases."

KYV-101 will be evaluated for safety and tolerability in the new indication in the KYSA-6 trial. KYV-101 is also being evaluated in patients with lupus nephritis in the phase 1 KYSA-1 trial (NCT05938725) in the US and the phase 1/2 KYSA-3 clinical trial in Germany. For patients with diffuse cutaneous systemic sclerosis (scleroderma), KYV-101 is being assessed in the phase 1/2 KYSA-5 trial in the US.

1. Myasthenia Gravis Awareness. Premier Neurology and Wellness Center. Website. Accessed June 12, 2024.,to%20support%20individuals%20with%20MG.
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