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Novartis has urgently paused eight clinical trials of its experimental autoimmune disease treatment, rapcabtagene autoleucel (rap-cel), after three trial participants died from a severe immune reaction. The Swiss drugmaker initiated the hold once it was notified of the deaths, which were linked to immune effector cell-associated hemophagocytic syndrome (IEC-HS), a rare but potentially life-threatening inflammatory response that can occur after CAR-T cell therapy.
The trials were testing rap-cel, a CD19-targeted CAR-T cell therapy, in several autoimmune and neurological conditions including lupus, multiple sclerosis, rheumatoid arthritis, and myasthenia gravis. According to a company spokesperson, all screening, randomization, and treatment administration in affected studies have been suspended while Novartis conducts a comprehensive review of safety and clinical data. Patients who already received the treatment will continue to be monitored in line with trial protocols.
The pause does not apply to ongoing studies of rap-cel for cancer indications, which remain unaffected. Novartis is now working with independent data committees to identify the causes of the adverse events and to develop improved safety measures, such as closer monitoring and earlier detection of immune reactions.
Bristol Myers Squibb (BMS) has also decided to pause enrollment in some of its own CAR-T trials for autoimmune diseases after observing transient, reversible inflammatory events with its investigational therapy, zolacabtagene autoleucel (zola-cel). BMS stated that it is reviewing safety data "out of an abundance of caution." No deaths have been reported in BMS’s paused trials, but at least one case of IEC-HS had previously been documented.
IEC-HS is considered a rare but serious side effect in CAR-T therapies, most commonly reported in blood cancer treatments. The cause of IEC-HS in these cases is still being investigated. Some industry analysts suggest that rapid manufacturing processes for these cell therapies, or certain patient characteristics, might increase risk, but other factors could also contribute.
The immediate future of the paused studies depends on the outcome of these safety reviews. Other companies developing similar CAR-T therapies for autoimmune diseases are watching developments closely, as the results may impact patient selection, manufacturing, and monitoring protocols for all ongoing and planned trials in this area.