The cost-effectiveness of gene therapy for severe hemophilia B: a microsimulation study from the United States perspective

Abstract

Adeno-associated virus (AAV)-mediated gene therapy is a novel treatment promising to reduce morbidity associated with hemophilia. While multiple clinical trials continue to evaluate efficacy and safety, limited cost-effectiveness data have been published. This study compared the potential cost-effectiveness of AAV-mediated factor IX(FIX)-Padua gene therapy for severe hemophilia B patients in the United States (US) to on-demand FIX replacement and primary FIX prophylaxis, using either standard or extended half-life FIX products. A microsimulation Markov model was constructed and transition probabilities between health states and utilities were informed by published data. Costs were aggregated using a micro-costing approach. An 18-years-old till death time-horizon from the perspective of a third-party payer in the US was conducted. Gene therapy was more cost-effective than both alternatives considering a $150,000/QALY threshold. The price for gene therapy was assumed $2,000,000 in the base-case scenario, yet one of the one-way sensitivity analyses was conducted using observed manufacturing, administration and five-year follow-up cost of $87,198 for AAV-mediated gene therapy vector as derived from the manufacturing facility and clinical practice at St. Jude Children's Research Hospital. One-way sensitivity analyses showed 10/102 scenarios in which gene therapy was not cost-effective compared to alternative treatments. Notably, gene therapy remained cost-effective in a hypothetical scenario in which we estimated that the discounted factor concentrate price was 20% of the wholesale acquisition cost in the US. Probabilistic sensitivity analysis estimated gene therapy cost-effective at 92% of simulations considering $150,000/QALY threshold. In conclusion, based on detailed simulation inputs and assumptions, gene therapy was more cost-effective than on-demand treatment and prophylaxis for patients with severe hemophilia B.

Haemophilia gene therapy—Update on new country initiatives

“…However, the observed costs for vector manufacturing, administration and 5-year follow-up have been reported at about US$ 88,000/dose for AAV-mediated gene therapy. 47,48 Even in HIC, there is no resolution or consensus on payment models. 49 For LMIC health authorities to consider supporting gene therapy, the availability of data on safety, efficacy, health outcomes, cost and cost-effectiveness and resource requirements as relating to their own socio-economic environment is important.…”

“…This price range aligns with cost‐effectiveness analysis in HIC in relation to expenses for current CFC‐based therapy and prophylaxis. However, the observed costs for vector manufacturing, administration and 5‐year follow‐up have been reported at about US$ 88,000/dose for AAV‐mediated gene therapy 47,48 . Even in HIC, there is no resolution or consensus on payment models 49 .…”

Gene Therapy and Hemophilia: Where Do We Go from Here?

“…On the other hand, our study 84 and the report generated by the Institute for Clinical and Economic Review (ICER) 83 both analyzed an 18 years old to death time horizon. However, the results are incomparable because each assessed gene therapy for a different type of hemophilia, hemophilia B for the former and hemophilia A for the latter, with very different assumptions regarding the long-term effectiveness of gene therapy.…”

Gene therapy in haemophilia: literature review and regional perspectives for Turkey

“… 16 Moreover, gene therapy was likely to be cost-effective compared with on-demand treatment and prophylaxis for patients with severe haemophilia, whereas the annual costs exceed $100,000 per patient. 17 , 18 …”