OBJECTIVES: Despite progress in the gene therapy landscape, challenges remain around therapies demonstrating long-term safety and efficacy with robust clinical trials. This study analyses health technology assessment (HTA) perceptions of gene therapies, focusing on trial design, safety/efficacy, costs, and potential learnings for emerging therapies.

METHODS: Qualitative analyses were conducted from 23 publicly available HTA reports for onasemnogene abeparvovec, atidarsagene autotemcel, betibeglogene autotemcel, voretigene neparvovec and eladocagene exuparvovec across EU4, England, and the US (ICER reports). HTA agencies’ critique on 3 categories were considered:

1. 1. Trial Design: sample size, trial type, patient population, trial duration and limitations with indirect treatment comparisons;
   2. Safety and Efficacy: safety, overall survival, morbidity endpoints, disease modification, patient reported outcomes and durability of response;
   3. Unmet needs and costs: disease burden, unmet need, cost-effectiveness estimates and budget impact.

RESULTS: Consistent concerns with trial design, durability of response and budget impact were identified. However, positive HTA decisions were possible across markets, with reimbursement without population restrictions in some. High unmet need perceived across disease areas likely influenced overall HTA outcomes, although the G-BA does not officially use unmet need as a key value driver during benefit assessments. Three therapies in Germany achieved a hint of non-quantifiable/no added benefit rating, however both atidarsagene autotemcel and voretigene neparvovec achieved added benefit ratings, despite concerns on trial design.

CONCLUSIONS: Gene therapies hold great promise, but uncertainties in their durability and costs remain. Manufacturers must consider ways to optimise their trial design and present a compelling case regarding the unmet need and burden of disease, given that these appear to be strong influencing factors in HTA evaluations.