OBJECTIVES: AAV-mediated gene therapy (AAVGT) is a novel treatment offering curative effects for several genetic diseases. The high upfront cost of AAVGT and the uncertainty around durability of its effectiveness are posing challenges for health economists. The ISPOR taskforce compiled a list of special considerations, including exploring different discounting rates (DRs). We examined the impact of different DRs when comparing AAVGT to alternative treatments in persons with hemophilia A.

METHODS: We conducted a microsimulation Markov model using a lifetime horizon to analyze the cost-effectiveness of AAVGT preceded and followed by standard half-life (SHL) factor VIII prophylaxis (Pro) compared to lifelong on-demand (OD) SHL and extended half-life (EHL) and lifelong Pro with SHL and EHL. In the base-case scenario, we used 3% DR for both costs and quality adjusted life years (QALYs). We conducted 6 scenario analyses varying the DR: 1) 0% for both costs and QALYs, 2) 5% for both costs and QALYs, 3) 4% costs, 1.5% QALYs, 4) 4% costs, 2% QALYs, 5) 5% costs, 1.5% QALYs, and 6) 5% costs, 2% QALYs.

RESULTS: Base case results showed AAVGT–SHL not cost-effective compared to OD–SHL or OD–EHL with incremental cost-effectiveness ratio (ICER) of $1,060,000/QALY and $1,050,000/QALY, respectively and dominant compared to Pro–SHL and Pro–EHL. Varying DR did not change the results with one exception, with 0% DR, AAVGT–SHL became cost-effective instead of dominant, compared to Pro–SHL with ICER of $140,000/QALY. AAVGT–SHL remained dominant compared to Pro in all other scenarios. Compared to OD, AAVGT–SHL was not cost-effective in any of the scenarios with ICER ranging between $460,000/QALY–$1,340,000/QALY.

CONCLUSIONS: Although the variation in DR changed the cost-effectiveness outcome in only one scenario, from dominant to cost-effective, the range of ICER varied widely depending on different DRs, indicating the significant influence of different DRs.