Published in The Lancet Neurology, a study led by James Howard, MD, professor of neurology at the UNC School of Medicine, showed how an RNA CAR-T therapy developed by Cartesian Therapeutics can dramatically improve symptoms in patients with myasthenia gravis, an autoimmune disorder.
Cartesian Therapeutics, a clinical-stage biotechnology company pioneering cell therapies for autoimmune diseases, announced today the publication of a landmark paper in The Lancet Neurology, describing a cutting-edge RNA CAR-T (rCAR-T) therapy administered to patients with generalized myasthenia gravis (MG), a debilitating autoimmune neurological disease. The data demonstrate marked and long-lasting clinical improvement in patients with MG. This is the first clinical trial using rCAR-T to treat autoimmunity, and the first successful phase 2 trial using an engineered cell therapy to treat autoimmunity.
“Conventional, DNA-engineered CAR T-cells are highly effective in treating several blood cancers, but associated toxicities and the need for lymphodepletion chemotherapy limit their use beyond oncology,” said Dr. Miloš Miljković, Chief Medical Officer at Cartesian. “To expand the capabilities of cell therapy to new areas and improve safety, we engineered CAR T-cells with RNA and used them to treat patients with MG.”
The study enrolled 14 patients with generalized MG, a chronic autoimmune disorder that causes disabling muscle weakness and fatigue. For most individuals, the disease is characterized by the presence of antibodies against the acetylcholine receptor, a protein found on the surface of nerve cells that plays a key role in muscle contraction. There is currently no cure for MG, and treatment typically requires chronic immunosuppressive medicines, with their attendant risks and side effects.
In this study, patients received six infusions of rCAR-T therapy, administered as an outpatient treatment, without lymphodepletion. Patients were followed for a median duration of six months. The clinical trial data indicated that the therapy was well tolerated, with no dose-limiting toxicities, cytokine release syndrome, or neurotoxicity. Clinical improvements were marked and long-lasting across four validated MG disease scoring systems. Strikingly, at six months, the average improvements were about 3-fold greater than thresholds considered clinically meaningful. Clinical benefit was sustained long-term for most patients, even months after completing the course of therapy. Three patients achieved complete or near-complete eradication of all disease symptoms; two other patients who relied on chronic IVIg therapy prior to enrollment ceased to need this therapy after Descartes-08 treatment.
“Currently, the mainstay of myasthenia therapy is chronic use of broad immunosuppression, which has many drawbacks,” said James Howard, MD, professor of neurology at University of North Carolina School of Medicine and a senior author on the paper. “The prospect of inducing potent, durable responses and reducing or eliminating use of immunosuppressive therapy is very appealing to the myasthenia community. Based on the compelling results of this paper, we are now enrolling patients with MG into a randomized placebo-controlled study, the first study of its kind for an engineered adoptive cell therapy.”