Modelling benefits, costs and affordability of a novel gene therapy in hemophilia A

Abstract The objective was to assess undertake an early cost-effectiveness assessment of valoctocogene roxaparvovec (valrox;Roctavian®) compared to factor (F)VIII prophylaxis or emicizumab (Hemlibra®) in patients with severe Hemophilia A (HA) without FVIII-antibodies. Secondary, weWe also aimed to incorporate and quantify novel measures of value such as treatment durability, maximum value-based price (MVBP) and break-even time (i.e., time until benefits begin to offset upfront payment). We constructed a A Markov-model was constructed to model bleeds over time which were linked to costs and quality-of-life decrements. In the valrox arm, FVIII% over time were first estimated combining initial effect and treatment waning and then linked to bleeds. In FVIII- and emicizumab-arms, bleeds were based on trial evidence. Evidence and assumptions were validated using via expert elicitation. Model robustness was tested via sensitivity analyses. A Dutch societal perspective was applied with a 10-year time-horizon. Valrox in comparison to FVIII, and emicizumab showed small increases in quality-adjusted life years atand lower costs, and was therefore dominant. Valrox’ base case MVBP was estimated at €2.65 million/treatment compared to FVIII and €3.5 million/treatment versus to emicizumab. Mean break-even time was 8.03 years compared to FVIII and 5.68 years to emicizumab. Early modelling cost-effectiveness analysis Treatment of patients with HA in the Netherlands treated with valrox was estimated to resultresulted in estimated improved health and lower cost compared to prophylactic FVIII and emicizumab. We also demonstrated feasibility to of incorporation ofmodelincorporate treatment durability was demonstrated and , as well as quantification of novel outcomes such as value-based pricing scenarios and break-even ti¬me. However, more work is needed to beter characterize uncertainties, define affordability and increase informativeness for decision making. Future work should aim to better characterize uncertainties and increase translation of early economic evaluationsmodelling to direct research efforts.