Novartis halted eight clinical trials for its experimental CAR-T cell therapy, rap-cel, in late August after three patients died from severe immune effector cell-associated hemophagocytic syndrome (IEC-HS), a life-threatening immune response. The trials were testing rap-cel in autoimmune conditions such as lupus, multiple sclerosis, rheumatoid arthritis, generalized myasthenia gravis, systemic sclerosis, and idiopathic inflammatory myopathies. The company initiated these holds on August 24 to conduct a comprehensive review of the safety events and is engaged with regulators regarding the findings.
Bristol Myers Squibb also voluntarily paused enrollment in its autoimmune trials for zolacabtagene autoleucel (zola-cel) out of an abundance of caution. The company reported detecting "transient and reversible inflammatory events" during routine safety surveillance and aims to complete its evaluation and resume testing as quickly as possible. Wall Street analysts have noted that the rapid manufacturing technology employed by both rap-cel and zola-cel, designed to speed up production compared to earlier CAR-T products, could be contributing to the increased cell expansion and reported toxicities.
The pauses by Novartis and Bristol Myers Squibb have raised questions about the broader autoimmune cell therapy landscape, causing shares in other companies developing similar treatments, such as Kyverna, Cabaletta Bio, Allogene Therapeutics, CRISPR Therapeutics, and Fate Therapeutics, to fluctuate. While analysts from William Blair and Jefferies acknowledge the risks, they suggest that a more cautious approach to manufacturing, study enrollment, and side effect management, including improved awareness and treatment for IEC-HS, could help mitigate future safety hazards. Some analysts also highlight that companies like Cabaletta and Kyverna use more traditional, standardized production processes or exclude high-risk patients, potentially reducing severe immune responses.
