Novartis Halts 8 Autoimmune Trials After Three Patient Deaths, Bristol Myers Squibb Pauses Its Own CAR-T Program

Novartis confirmed Monday it paused eight clinical trials testing its experimental cell therapy rapcabtagene autoleucel, known as rap-cel, after three patients died from a rare and severe immune reaction, according to Fierce Biotech and BioPharma Dive. The company halted screening, randomization, and dosing across the affected studies on August 24, a Novartis spokesperson told multiple outlets including MedPage Today and BioSpace.

The deaths stemmed from immune effector cell-associated hemophagocytic syndrome, or IEC-HS, a condition in which the body's engineered immune cells multiply rapidly and trigger a massive inflammatory response that damages organs and tissue, according to Pharmaphorum. Complications from the reaction proved fatal in all three cases, Novartis said.

Bristol Myers Squibb separately paused enrollment in its own autoimmune trials of a similar therapy, zolacabtagene autoleucel, or zola-cel. A BMS spokesperson told BioPharma Dive the move was made "out of an abundance of caution" after the company detected "transient and reversible inflammatory events" during routine safety monitoring. BMS reported no deaths in its program and said zola-cel's safety profile "remains consistent with the known profile of CAR-T therapies."

What's Paused, What Isn't

The Novartis trials cover systemic lupus erythematosus, lupus nephritis, systemic sclerosis, ANCA-associated vasculitis, idiopathic inflammatory myopathies, rheumatoid arthritis, Sjögren's disease, generalized myasthenia gravis, and two forms of multiple sclerosis, according to trial identifiers Novartis gave Fierce Biotech. Studies of rap-cel in cancer, including high-risk large B-cell lymphoma, are continuing, the company said.

BMS's zola-cel program targets lupus, systemic sclerosis, myositis, rheumatoid arthritis, autoimmune cytopenia, and other conditions. According to BioPharma Dive, BMS was scheduled to begin a new systemic sclerosis trial this month before the pause. It remains unclear whether BMS's suspension covers every study in the program; a company spokesperson told BioSpace that detail hasn't been disclosed.

Why This Is Different From Cancer Trials

IEC-HS is a known, rare complication in CAR-T cancer treatment. FDA-approved cancer versions of CAR-T carry a boxed warning about it, according to MedPage Today. What changes the calculus here is the patient population. Cancer patients facing a terminal diagnosis often accept serious treatment risk. Lupus and multiple sclerosis, while debilitating and life-shortening in some cases, are not typically immediately fatal, which raises the bar for what risk is acceptable.

Patients with autoimmune diseases who have failed every conventional therapy have seen what MedPage Today called "astonishing" results from CAR-T, including long-lasting remission. Advocates for continuing this research have a legitimate point: halting these programs, even temporarily, delays a treatment that some patients with no other options were counting on. That concern deserves to be taken seriously rather than waved off because three deaths occurred.

But three deaths in trials for non-terminal diseases is a serious safety signal regulators and drugmakers can't ignore. Novartis said it is now working with independent data safety monitoring boards to review the events and figure out how to catch dangerous reactions earlier, according to Fierce Biotech.

A Manufacturing Question Nobody Has Answered Yet

Both rap-cel and zola-cel use newer manufacturing technology designed to produce CAR-T cells faster than earlier products. William Blair analyst Sami Corwin wrote in a Monday client note, cited by BioPharma Dive, that this faster process "could be driving increased cell expansion and the reported toxicities," though she cautioned other factors could be involved. Novartis has not attributed the deaths to the manufacturing method.

The Stock Move Isn't What It Looks Like

Reuters, via WHBL, reported Novartis shares rose 4% on Tuesday. The gain reflected unrelated positive late-stage trial results for Novartis's oral multiple sclerosis drug, remibrutinib. Investors were reacting to that news, not shrugging off three patient deaths.

What Comes Next

Novartis said it is sharing information with health authorities and continuing to monitor patients who already received rap-cel. No regulatory action, such as an FDA clinical hold, has been announced by either company or reported by any source here. BMS said it aims to complete its safety review and resume enrollment "as quickly as possible," but gave no target date. Until both reviews conclude, patients enrolled in eight rap-cel and three zola-cel trials, according to ClinicalTrials.gov listings cited by MedPage Today, are in limbo waiting to find out whether the treatment that gave some of them their first real remission will come back online and under what new safety rules.