The Top Line · Fierce Life Sciences

Autoimmune CAR-T: Navigating the FDA’s new regulatory playbook

·23 min·1 clip

Singh says toxicity management with tocilizumab ports over from oncology, but endpoint selection will be 'quite different and quite novel.'

1. The Top Line from Fierce Pharma and Fierce Biotech, recorded February 27, examines the FDA's Annals of Internal Medicine article on how autoimmune CAR-T therapies should be developed. 2. Host Ayla Ellison introduces Fierce Pharma's Angus Liu, who interviews Dr. Harpreet Singh, Chief Medical Officer at Precision for Medicine and a former FDA Oncology Division Director who spent nearly a decade at the agency. 3. The central question is how much of the oncology CAR-T playbook carries over to lupus and myasthenia gravis, as Caverna is poised to file the first autoimmune CAR-T application. 4. Singh summarizes the article by Vinay Prasad and two CBER colleagues as supportive but cautious, emphasizing durability, long-term safety, a refractory definition of failure of at least two prior immunosuppressants, and a 'case-by-case' approach. 5. She notes the format is unusual, saying publication in an 'ideas and opinion section' of a journal is not business as usual unless a formal draft guidance follows. 6. On follow-up, Singh explains that the 15-year window reflects viral vector persistence and delayed toxicities up to 10 years, including secondary malignancies, and adds that the seven-year REMS reevaluation led to those warnings being dropped from labels. 7. Liu relays Georg Schett's view from the University of Erlangen-Nuremberg that autoimmune patients lack prior genotoxic exposure and need only a quick immune 'reset', and Singh does not disagree with the different risk profile but expects FDA to default to oncology data given that CAR-T entered autoimmune disease only in 2021. 8. Singh suggests the article's focus on pediatric development and fertility could justify follow-up even longer than in oncology, since patients are being treated at younger ages. 9. She proposes an FDA-led data-sharing initiative that groups safety data by antigen and disease to inform how long patients need to be followed, and says sponsors should arrive with clear monitoring plans mixing objective and subjective disease measures. 10. Suited to biotech sponsors, regulatory professionals, and CAR-T industry watchers.

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