Novartis paused eight clinical trials of its experimental cell therapy rap-cel on 24 August after three patients died from immune effector cell-associated hemophagocytic syndrome, a life-threatening immune reaction.
The paused studies cover conditions including lupus, rheumatoid arthritis, vasculitis, multiple sclerosis and myasthenia gravis. They had enrolled more than 500 patients. Two Novartis trials involving patients with lymphoma and leukemia were not affected by the hold.
Novartis said the reaction is a known, potentially life-threatening risk of chimeric antigen receptor T-cell, or CAR-T, therapy. The company said it is reviewing the deaths with independent safety boards and sharing information with health authorities. It will continue to monitor patients who have already received rap-cel.
Immune effector cell-associated hemophagocytic syndrome is a dangerous disorder in which the body’s immune defences turn against its own organs. The company has not disclosed whether the three deaths occurred in one trial or across multiple studies. It was also not immediately clear when the deaths occurred or what clinical circumstances preceded each fatal case.
The suspension became public after Sami Corwin, an analyst at William Blair, identified a cluster of studies that had simultaneously stopped activity while reviewing a clinical trials database.
Rap-cel is a CAR-T cell therapy candidate being developed for autoimmune and neurological disorders. CAR-T therapies modify a patient’s immune cells to recognise a specific target and destroy cancer cells. Rap-cel works by removing a patient’s own immune cells, engineering them in a laboratory to hunt down and kill malfunctioning cells, then infusing them back into the body.
The approach was originally developed for oncology. Its use in autoimmune disease remains experimental. The trial pause affects a programme spanning several conditions while leaving Novartis’s lymphoma and leukemia trials intact.
Bristol Myers, which is developing the competing CAR-T treatment zolacabtagene autoleucel, or zola-cel, voluntarily halted enrolment in its own trials as a precaution. The company said the pause was made “out of an abundance of caution” so it could review safety data across its programme.
A Bristol Myers spokesperson said the company had detected inflammatory events during routine surveillance. The spokesperson said those events were temporary and reversible, and none was fatal. Bristol Myers notified regulators and researchers of its pause in early June, though the information stayed out of public view for about three months.
It remains unknown whether the deaths linked to rap-cel reflect a risk shared across CAR-T therapies or a risk specific to rap-cel’s design. The available information also does not establish whether similar risks exist in Bristol Myers’s zola-cel programme. Health authorities’ actions or planned actions in response to the Novartis deaths have not been disclosed.
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