Cost-Effectiveness of Emicizumab for Prophylaxis in People with Severe Hemophilia A without Inhibitors

Background: With the entry of gene therapy into the hemophilia A treatment landscape, healthcare decision makers are re-evaluating the relative value of different prophylaxis options for people with hemophilia A (PwHA) without inhibitors. While there are multiple elements of value to consider when conducting a clinical and economic assessment of treatments for PwHA, this study aims to answer questions about the relative cost-effectiveness of prophylactic therapies.

Methods: A Markov model was used to estimate the cost-effectiveness of emicizumab compared to: valoctogene roxaparvovec gene therapy, standard half-life factor VIII (FVIII) , and extended half-life FVIII replacement products. Health states in the model included: life with no arthropathy, life with arthropathy, life after joint replacement surgery, and death. Parameter estimates, including annualized bleed rates and durability of treatment (Table 1), were estimated from clinical trial and real-world data. Costs included the wholesale acquisition cost of drugs, treatment of bleeds, and management of hemophilia-related joint disease, which were estimated from published literature. The cost of gene therapy was assumed to be a one-time cost of $2.5 million (in 2022 US Dollars) per treated patient. Utilities were derived from patient-reported outcomes in published real-world data. Incremental cost-effectiveness (ICER) was estimated in cost per quality-adjusted life-year (QALY) gained, from a payer perspective over a 2-year, 5-year, and a lifetime horizon.

Results: Compared to gene therapy, emicizumab was estimated to be less costly (-$1.395 million) with similar effectiveness (0.00 QALY incremental difference) over a 2-year horizon, less costly and more effective over a 5-year horizon (-$125,215; 0.02 QALY), and more costly but cost-effective over a lifetime horizon ($8,945; 0.95 QALY; ICER $9,406/QALY). Compared to standard half-life FVIII prophylaxis and extended half-life FVIII prophylaxis, emicizumab was dominant (less costly and more effective) over each model time horizon.

Conclusions: Emicizumab remains a highly cost-effective prophylaxis strategy compared with FVIII prophylaxis in adult PwHA. Uncertainties around the effectiveness and durability of gene therapy make assessment of 2 and 5-year cost-effectiveness challenging, but over a lifetime emicizumab appears to be cost-effective compared with gene therapy for PwHA. Given the uncertainties related to new therapies, additional sensitivity analyses are needed to estimate the value of therapies under different scenarios and to consider other elements of value that are important to PwHA.

Decker-Palmer:Genentech, Inc.: Current Employment; Roche Holding: Current equity holder in private company, Current equity holder in publicly-traded company. Lin:Genentech, Inc.: Current Employment; Roche: Current equity holder in publicly-traded company. Wilson:RTI Health Solutions: Current Employment; Genentech, Inc.: Research Funding. McDade:RTI Health Solutions: Current Employment; Genentech, Inc.: Research Funding. Bawa:Genentech, Inc.: Current Employment; Genentech/Roche: Current equity holder in publicly-traded company. Kowal:Genentech, Inc.: Current Employment, Current equity holder in private company; Genentech/Roche: Current equity holder in private company. Ravelo:Genentech/Roche: Current Employment; Roche: Current equity holder in private company, Current holder of stock options in a privately-held company. Yu:Genentech/Roche: Current Employment; Roche: Current equity holder in publicly-traded company. Ko:Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company.