OBJECTIVES: One-time gene therapies (GTs) have had varying success in convincing cost-effectiveness (CE)-focused markets of their long-term durability. In CE markets, there has not been a consistent approach to the assumptions made around durability within economic models. This research aims to understand how GT durability is assumed in economic models and what evidence is necessary to successfully prove decades worth of durability.

METHODS: The appraisals of three GTs (onasemnogene abeparvovec, voretigene neparvovec, etranacogene dezaparvovec) by the Canadian Agency for Drugs and Technologies in Health (CADTH) (now Canada’s Drug Agency) and the National Institute for Health and Care Excellence (NICE), were analysed to understand the methodology used to assess durability within the Health Technology Assessments (HTAs). The analogue analyses were then validated using insights from primary research with former payers from CADTH and NICE (N=6).

RESULTS: Onasemnogene abeparvovec, was assumed to have 80 years of durability by both CADTH and NICE. Voretigene neparvovec was assumed to have 10 years of durability by CADTH, compared to 40 years for NICE. The key difference in outcome being NICE accepted the biological rationale for the maintenance of treatment effect. Lastly, durability of effect for etranacogene dezaparvovec was not assumed by NICE (not yet assessed by CADTH) due to the low number of patients, lack of long-term data and clinical expert opinion on biological rationale.

CONCLUSIONS: When developing economic models in Canada and the UK, durability of a GT is informed by clinical data, biological plausibility and required duration of effect estimated from a variety of sources. Manufacturers can optimise appraisal outcomes of GTs in these two markets by providing a robust data package with adequate patient numbers (relative to the disease), sufficient long-term follow-up, and support from clinical experts on the biological rationale for durability of the therapy.