Objectives: Hemophilia A is a rare genetic bleeding disorder associated with high morbidity and significant financial burden. For bleed prevention, about 80% of patients use prophylaxis, 20% on-demand infusions of either standard half-life factor VIII products (SHL-FVIII) or the newer extended half-life products (EHL–FVIII). Adding heterogeneity to the treatment paradigm, gene therapy is a new promising treatment being evaluated for hemophilia and multiple other genetic pathologies. Our study examined the cost-effectiveness of eight treatment strategies: on-demand and prophylaxis using either SHL-FVIII or EHL-FVIII, with and without gene therapy.

Methods: We constructed a microsimulation Markov model analyzing a lifetime horizon, from a societal perspective in the United States, with gene therapy administered at age 18 years. An annual discounting rate of 3% was applied. Model input parameters were obtained from the literature. Gene therapy price was assumed at $2,000,000/patient. We extrapolated waning therapeutic response based on 5-years clinical trial follow-up and estimated that patients would restart prophylaxis/on-demand after 6 years.

Results: For prophylaxis, costs and quality adjusted life years (QALYs) were $20,144,062|23.18, $24,147,829|23.73, $19,703,755|24.12, and $23,383,234|24.57 for SHL–FVIII alone, EHL–FVIII alone, SHL–FVIII+Gene therapy and EHL–FVIII+Gene therapy, respectively; for on-demand strategy, costs|QALYs were $8,234,037|14.23, $8,764,330|14.67, $8,896,892|15.36 and $9,378,153|15.66, respectively. Considering a $150,000/QALY threshold, gene therapy was dominant compared to prophylaxis but not cost-effective compared to on-demand strategy. At a gene therapy price of $625,000 and $1,925,000, SHL–FVIII+Gene therapy would be cost-effective compared to on-demand SHL–FVIII and on-demand EHL–FVIII, respectively.

Conclusion: This is the first model to assess health policy benefits for the whole hemophilia population rather than only the gene therapy-eligible group, by including individuals with FVIII inhibitors and/or adeno-associated virus antibodies. Our results suggest if current gene therapy products are only effective for 6 years, the commercially proposed $2,000,000 price point will not be cost-effective for all patient subgroups.