Swiss drugmaker Novartis has temporarily halted eight clinical trials for its experimental cell therapy, rap-cel, which targets autoimmune and neurological disorders. This decision followed the deaths of three patients who experienced a severe immune response known as immune effector cell-associated hemophagocytic syndrome (IEC-HS). Novartis's rap-cel works by genetically engineering a patient's own immune cells to combat malfunctioning cells. The company was testing rap-cel in conditions such as lupus, multiple sclerosis, systemic sclerosis, rheumatoid arthritis, and myasthenia gravis, but cancer studies are unaffected. Novartis initiated the holds on August 24 and is currently conducting a comprehensive review of the safety events, engaging with regulators.
Separately, Bristol Myers Squibb also paused enrollment in its autoimmune trials for zolacabtagene autoleucel (zola-cel), another CAR-T treatment. This move was made out of an abundance of caution to review clinical data after detecting "transient and reversible inflammatory events" during routine safety surveillance. Both Novartis's rap-cel and Bristol Myers Squibb's zola-cel utilize technology designed for rapid production, which some analysts, including William Blair analyst Sami Corwin, suggest could be contributing to increased cell expansion and the observed toxicities.
The trial halts have raised concerns across the broader autoimmune cell therapy landscape. Shares of companies like Kyverna, Cabaletta Bio, Allogene Therapeutics, CRISPR Therapeutics, and Fate Therapeutics, which are also developing autoimmune cell therapies, saw initial dips before recovering. Analysts are now assessing the impact, with some suggesting that the faster production processes used by Novartis and Bristol Myers could be a factor in the adverse events. Other companies, such as Cabaletta, are using more traditional, longer production methods and have reported lower rates of adverse events, including no cases of IEC-HS, and actively exclude high-risk patients to minimize inflammatory responses.
