Novartis and Bristol Myers Squibb have paused multiple trials evaluating their respective cell therapy programs against autoimmune conditions after observing inflammatory side effects in testing, the companies confirmed Monday afternoon.
Novartis, which is testing a personalized cell therapy called rap-cel in a handful of autoimmune studies, found three cases of immune effector cell-associated hemophagocytic syndrome, a rare and possibly life-threatening reaction. The company said it initiated holds on those trials — which are evaluating rap-cel in lupus, myasthenia gravis, multiple sclerosis and more — on Aug. 24. Novartis is “engaged” with regulators and is reviewing the findings, according to a company spokesperson.
“The temporary halt will allow for a more comprehensive review of the evolving clinical and safety data across the program,” the spokesperson wrote in an email to BioPharma Dive.
Bristol Myers has also voluntarily paused enrollment in autoimmune trials evaluating its own CAR-T treatment zolacabtagene autoleucel, or zola-cel. In an email to BioPharma Dive, a company spokesperson said the move was made “out of an abundance of caution” to “review clinical data across our zola-cel program,” noting that Bristol Myers detected “transient and reversible inflammatory events” during routine safety surveillance. The company aims to complete the evaluation and resume testing “as quickly as possible.”
Results published in February detailed one case of IEC-HS in a Phase 1 study of zola-cel. The drug’s safety profile "remains consistent with the known profile of CAR-T therapies,” according to the spokesperson.
“We continue to have confidence in zola-cel, which has demonstrated transformational, treatment-free responses in [systemic lupus erythematosus] and other autoimmune diseases,” the spokesperson added.
Novartis is testing rap-cel in eight different immunology and neuroscience indications. Studies testing rap-cel in cancer are still ongoing, a spokesperson said.
Bristol Myers was set to begin a trial of zola-cel in patients with systemic sclerosis this month.
Both rap-cel and zola-cel are being developed with technology that’s meant to speed up production compared to earlier CAR-T products. That technology “could be driving increased cell expansion and the reported toxicities,” wrote William Blair analyst Sami Corwin, though she cautioned in a Monday client note that other factors could be involved too.
Novartis and Bristol Myers are leaders in cell therapy development. Both have brought to market products used to treat certain cancers. They’re also at the forefront of a broad research effort to redirect those kinds of cell therapies against autoimmune diseases. Early academic research has shown the approach might help drive tough-to-treat inflammatory conditions, like lupus, into long-lasting remissions.
Several other biotechs are testing their own CAR-T therapies on autoimmune conditions. Cabaletta Bio has multiple trials underway, including a late-stage study in myositis. Kyverna Therapeutics could submit an approval application in stiff person syndrome by the end of the year and is enrolling patients in a pivotal study in myasthenia gravis.
“This will clearly need to be monitored to determine how it could impact the total market adoption of these products in the future,” Corwin wrote.
