Novartis Halts Eight Trials of rap-cel, a CAR-T Therapy for Autoimmune and Neurological Diseases, After Three Deaths
Novartis Halts Eight Trials of rap-cel, a CAR-T Therapy for Autoimmune and Neurological Diseases, After Three Deaths
On 24 August, Novartis suspended trials of rap-cel, a CAR-T therapy being studied for autoimmune and neurological diseases. Three patients developed IEC-HS, a severe immune reaction, and all three died from its complications. Two oncology trials of rap-cel are continuing.
CAR-T therapy uses a patient’s own T-cells, which are immune cells capable of identifying a target. The cells are equipped with an artificial receptor that directs them to a selected protein. In rap-cel, this receptor recognizes CD19 on B-cells. B-cells are immune cells that produce antibodies, some of which attack the body’s own tissues in autoimmune diseases.
The aim is to eliminate the B-cells that sustain this attack and allow the B-cell population to develop again. In a 2022 study, five patients with severe lupus that had resisted several immunosuppressive drugs received CD19 CAR-T. All achieved remission within three months, and the B-cells that subsequently returned had a naive phenotype, which is characteristic of cells that have not yet formed immune memory. Following this early result, researchers began testing CAR-T therapies in a wider range of autoimmune diseases. By May, the registry listed 280 such trials.
rap-cel was one of these programs. According to Reuters, Novartis halted eight trials in lupus, rheumatoid arthritis, vasculitis, multiple sclerosis, myasthenia gravis, and other diseases. The company is reviewing the events with independent safety boards, which are groups of external experts that monitor clinical trials, and is looking for ways to detect dangerous adverse effects earlier.
At around the same time, Bristol Myers Squibb temporarily suspended enrollment in autoimmune disease trials of another CD19 CAR-T therapy, zola-cel. During a routine safety review, the company identified temporary, reversible inflammatory reactions and decided to reassess the program’s clinical data, BioPharma Dive reports.