Novartis, BMS Pause Autoimmune CAR-T Trials After Safety Events

Novartis has suspended several autoimmune and neurology trials of its investigational CD19 CAR-T therapy rapcabtagene autoleucel (rap-cel) after 3 patients died following serious cases of immune effector cell-associated hemophagocytic syndrome (IEC-HS).^1,2 Bristol Myers Squibb has separately paused at least some studies of its own CAR-T candidate, zolacabtagene autoleucel (zola-cel), after observing transient and reversible inflammatory events in its autoimmune development program.^1,2

A Novartis spokesperson confirmed the suspension in a statement, saying the 3 IEC-HS cases led to complications that ultimately proved fatal.¹ The pause affects the phase 2 AUTOGRAPH studies evaluating rap-cel in systemic lupus erythematosus, systemic sclerosis, and idiopathic inflammatory myopathies (NCT06665256), along with phase 1/2 trials in rheumatoid arthritis and Sjogren disease (NCT07048197), generalized myasthenia gravis, and certain types of multiple sclerosis.¹ Studies of rap-cel in cancer are not affected by the pause.¹

Novartis is reviewing safety data as BMS acts out of caution

Novartis said it is analyzing safety data to identify the factors that may have contributed to the fatal complications and is working with independent data monitoring committees on enhanced safety measures, including tighter patient monitoring, earlier identification of adverse events, and improved management strategies.¹

BMS, describing its decision as a step taken out of an abundance of caution, confirmed it is voluntarily pausing at least some zola-cel studies to review clinical data across the therapy's development program.^1,2 The company has ongoing zola-cel trials across several autoimmune indications, including myasthenia gravis, multiple sclerosis, and rheumatoid arthritis, though it remains unclear whether the pause extends to all of them.¹ No deaths have been reported in connection with zola-cel; a single prior case of IEC-HS involving the therapy was described in results published in February from a phase 1 study.² "The drug's safety profile remains consistent with the known profile of CAR-T therapies," a BMS spokesperson said.²

Analysts point to rapid manufacturing as a possible contributing factor

IEC-HS is a rare but serious adverse event previously reported with CD19 and BCMA-directed CAR-T therapies across blood cancer indications.¹ In a note to investors, analysts at William Blair pointed to rapid manufacturing, a feature shared by both rap-cel and zola-cel, as a possible contributor to the safety signals.¹ "Rapid manufacturing could be driving increased cell expansion and the reported toxicities," the analysts wrote, while also noting that indication-specific factors or a patient predisposition to a hyperinflammatory state could be playing a role.¹

The analysts cautioned that it remains difficult to extrapolate this risk to other CAR-T programs in development for autoimmune disease, noting that companies including Autolus, Cabaletta Bio, CRISPR Therapeutics, Kyverna Therapeutics, and Allogene Therapeutics are also developing CD19-directed CAR-T therapies for autoimmune indications.¹ Differentiated safety profiles among these competing programs could offer an advantage if development of the Novartis and BMS therapies remains constrained, according to the analysts.¹

Frequently Asked Questions

• What prompted Novartis to pause rap-cel trials in autoimmune disease?
  Three patients died after developing serious immune effector cell-associated hemophagocytic syndrome (IEC-HS) following treatment with rap-cel; the pause does not affect ongoing cancer studies of the therapy.
• Why did BMS pause zola-cel studies?
  BMS voluntarily paused at least some zola-cel trials after observing transient and reversible inflammatory events, describing the move as a precaution while it reviews clinical data across the program; no deaths have been reported.
• What might be driving these safety signals?
  Analysts have pointed to rapid manufacturing, a feature shared by both CAR-T candidates, as a possible contributing factor to increased cell expansion and toxicity, though indication-specific factors or patient predisposition may also play a role.

References
1. Manalac T. Novartis pauses CAR T studies due to 3 deaths; BMS follows suit after safety events. BioSpace. Published September 1, 2026. Accessed September 2, 2026. https://www.biospace.com/drug-development/novartis-pauses-car-t-studies-due-to-3-deaths-bms-follows-suit-after-safety-events
2. Novartis, Bristol Myers pause autoimmune CAR-T trials due to safety concerns. BioPharma Dive. Published September 1, 2026. Accessed September 2, 2026. https://www.biopharmadive.com/news/novartis-bristol-myers-autoimmune-cell-therapy-trial-halt/829218/