Novartis and BMS pause autoimmune CAR T trials over safety concerns
核心洞察
Novartis halted eight studies of rapcabtagene autoleucel on August 24 after three patients developed serious immune effector cell-associated hemophagocytic syndrome (搜索), with all three dying from complications.
The paused program includes phase II trials in systemic lupus erythematosus (搜索), lupus nephritis (搜索), systemic sclerosis (搜索), ANCA-associated vasculitis (搜索) and idiopathic inflammatory myopathies (搜索), plus phase I/II studies in other autoimmune indications.
Bristol Myers Squibb (搜索) separately paused enrollment in autoimmune trials of zolacabtagene autoleucel after observing transient and reversible inflammatory events during routine safety monitoring.
Novartis has halted eight clinical studies of its CD19 (搜索)-directed CAR T therapy rapcabtagene autoleucel (rap-cel) in autoimmune diseases after three patients developed serious immune effector cell-associated hemophagocytic syndrome (搜索) (IEC-HS). The company confirmed to Reuters that complications from the events led to the deaths of all three patients. Novartis described IEC-HS as a known, potentially life-threatening risk of CAR T treatment and said it is working with independent safety boards and health authorities to review the cases and identify ways to detect dangerous reactions earlier.
The affected program includes phase II trials in systemic lupus erythematosus (搜索) and lupus nephritis (搜索), systemic sclerosis (搜索), ANCA-associated vasculitis (搜索), and idiopathic inflammatory myopathies (搜索). Phase I/II studies in rheumatoid arthritis (搜索) and Sjögren's disease (搜索), generalized myasthenia gravis (搜索), relapsing multiple sclerosis (搜索), and non-active progressive multiple sclerosis have also been paused, according to Fierce Biotech. Screening, randomization, and treatment administration have stopped, while patients already treated continue to be monitored. Novartis said oncology studies of rap-cel in leukemia (搜索) and lymphoma (搜索) were not affected. Rap-cel is an autologous therapy manufactured using the company's T-Charge platform, designed to reduce the time cells spend in culture before infusion.
Bristol Myers Squibb (搜索) has separately paused enrollment in autoimmune disease trials of zolacabtagene autoleucel (zola-cel). The company told BioPharma Dive it observed "transient and reversible inflammatory events" during routine safety monitoring and implemented the pause as a precaution while reviewing clinical data. Zola-cel is another autologous CD19 (搜索)-directed therapy and uses Bristol Myers' rapid-manufacturing NEX-T platform; a phase I report published in February included one case of IEC-HS, BioPharma Dive reported. Bristol Myers said the therapy's overall safety profile remained consistent with the known risks of CAR T treatments and that it aims to resume enrollment after completing its review.
Source: The Medicine Maker