Assessing the potential cost-effectiveness of a gene therapy for the treatment of hemophilia A

Abstract

Aim: Hemophilia A is a genetic, chronic disorder classified by deficient or defective coagulation factor VIII (FVIII) that puts those affected at risk for spontaneous bleeding episodes, which lead to joint damage and chronic pain over time. Currently, most severe hemophilia A patients are treated with prophylactic FVIII, which requires costly and frequent infusions and lifelong adherence to medication. A gene therapy (valoctocogene roxaparvovec) is currently in development for the treatment of severe hemophilia A. This model assessed the potential cost-effectiveness of treating patients with valoctocogene roxaparvovec rather than prophylactic therapy. Materials and methods: We developed an individual-based, state-transition microsimulation model for assessing the likely cost-effectiveness of valoctocogene roxaparvovec compared to prophylactic FVIII. Men aged 30 with severe hemophilia A were modeled over a lifetime horizon, and costs were reported from the perspective of the United States health care system. Through microsimulation, patient-level heterogeneity was captured in starting weight, starting Pettersson score (PS), durability of valoctocogene roxaparvovec, and annual bleed rate (ABR). Results: The model projects that treatment with single-administration valoctocogene roxaparvovec would be cost-saving to people with hemophilia A at a price point comparable to other currently available gene therapy products due to its potential to reduce FVIII utilization, direct medical costs, lifetime bleeds, and accumulated joint damage. Limitations: The model relies upon evidence-based assumptions for clinical inputs due to limited data availability. Such uncertainty was mitigated by modeling heterogeneity across the population, specifically with regards to long-term gene therapy durability, lifetime bleed rates, and joint damage progression. Conclusion: Valoctocogene roxaparvovec was found to be cost-saving-on average by about $6.8 million per patient-and more effective than prophylactic therapy for treatment of hemophilia A. The comparative benefit of gene therapy was observed across a broad range of simulated patients that were representative of the real-world severe hemophilia A population.

Estimating the Financial Impact of Gene Therapy*

“…We have omitted the clinical costs of delivering gene therapy in our analysis, which are often higher than conventional therapeutics due to the need for inpatient hospital care. While there are cases where gene therapy is predicted to provide net cost-savings in treatment after accounting for the direct medical cost (e.g., valoctocogene roxaparvovec for the management of hemophilia A [80]), there is not yet evidence showing that gene therapy will result in net long-term cost savings. In addition, research has shown that new medical technologies generally raise health costs, and that cost-increasing changes in treatments outweigh cost-saving changes the majority of the time [102].…”

Hemophilia gene therapy—New country initiatives

“…Regulatory guidelines and requirements differ widely and are at different levels of development across countries, but often details are similar and aligned with regulations by the EMA or US FDA. The market price of vector may be high; however, detailed cost‐effectiveness analyses for prolonged or life‐time persistence of factor expression are needed for each country or region 82,83 . Such data will inform the development of adequate funding models and pricing strategies.…”

Gene therapy may not be as expensive as people think: challenges in assessing the value of single and short-term therapies

“…24 Zhou et al and Cook et al estimated approximately $23 million for lifetime medical costs associated with prophylactic FVIII. 25,26 Machin et al projected 10-year medical costs of approximately $2 million for prophylactic FVIII. 27 Croteau et al calculated annual FVIII drug costs of more than $700,000, 23 although a more recent estimate by Croteau et al suggests a lower range of $400,000-$550,000, 28 depending on alternative indicators of annual prophylactic use.…”

“…5,6 Cook et al constructed a lifetime CEA model of valoctocogene roxaparvovec with an assumed upfront price of $2 million and total medical cost of $17 million. 26 Both studies-assuming a decline in endogenous FVIII following valoctocogene roxaparvovec treatment-projected that valoctocogene roxaparvovec would be cost saving when compared with prophylactic FVIII. 5,6,26…”