OBJECTIVES: Rare genetic diseases pose a global challenge, with a high burden and few effective, long-term therapies. Cell and gene therapies (CGTs) offer a potentially durable solution, but immature data from small trials complicate health technology assessments (HTAs). Long-term durability is a key driver of CGT value. Therefore, it's critical to understand evolving techniques and assumptions for long-term durability in HTAs.

METHODS: We reviewed treatment durability assumptions and modeling methods of 10 CGTs in rare genetic diseases from 7 HTA bodies (UK, EU4, Canada, and US). In this analysis, treatment durability refers to the duration of a CGT’s treatment effect. Products assessed by a single HTA body were excluded from mean calculations.

RESULTS: Since 2018, 39 HTAs have been completed for 10 CGTs in 11 rare genetic diseases. All HTA bodies reviewed onasemnogene abeparvovec whereas exagamglogene autotemcel was only assessed by ICER. Products were evenly split between in vivo and ex vivo CGTs. Twenty-three HTAs used a long-term durability assumption, leading to a mean of 37.1 years. The assumed durability of CGTs ranged from 7 years (4/23 HTAs) to lifetime (9/23 HTAs). HAS was the most conservative, concluding that no durability assumption could be made for 4 CGTs and using a mean assumed durability of 19.0 years for the other 3 products assessed. AIFA was the most optimistic, assuming a lifetime durability for two CGTs. The assumed treatment durability across HTAs was widest for atidarsagene autotemcel (12 years to lifetime; n=3) and narrowest for voretigene neparvovec (10 to 40 years; n=4). Treatment waning was applied in 3/23 HTAs and cure proportion modeling was used in 9/23.

CONCLUSIONS: There are notable variations in the long-term durability assumptions of rare disease CGTs in HTAs. Modeling methods are evolving and building on past precedents. Further analysis is needed to unearth the most influential factors affecting durability assumptions.