Financing High-Cost Gene Therapy Under Clinical Uncertainty: Assessing Budget Impact of Reimbursement Models for Hemgenix® in Hemophilia B in Sweden

Aim Advanced therapy medicinal products, a European Union regulatory category encompassing gene-, cell-, and tissue-based medicines, challenge conventional reimbursement frameworks, particularly when a single administration entails high upfront costs and long-term effectiveness uncertainty. This study assessed the treatment-cost budget impact under three reimbursement models for etranacogene dezaparvovec (Hemgenix®) in hemophilia B within the high-income, decentralized, tax-financed healthcare system of Sweden. Methods Using a decision-support framework, an outcome-based annuity model was identified as a relevant reimbursement strategy for Hemgenix®. A cohort Markov model simulated per-patient treatment costs for payers for Hemgenix® and the comparator factor IX prophylaxis over 5, 10, and 15 years for a hypothetical cohort of adults with hemophilia B. Three reimbursement strategies—full upfront, 30% reduced upfront, and outcome-based annuity reimbursement—were compared with costs for factor IX prophylaxis under three scenarios: short-term trial outcomes, a full response, and partial response (10% annual failure rate). One-way sensitivity analyses examined varying treatment durability, cost of Hemgenix® and factor IX prophylaxis, mortality rates, and extended time horizon. Results Hemgenix® was more expensive than standard prophylaxis in the first 10 years under all scenarios and reimbursement strategies in Sweden. However, at 15 years, the 30% reduced upfront model and outcome-based annuity model incur lower treatment costs than prophylaxis in selected scenarios. Under sustained full treatment response, the reduced upfront reimbursement model showed the lowest treatment costs, while the outcome-based annuity model resulted in lower costs under partial and diminishing treatment effectiveness. Conclusion In this Swedish, budget-impact analysis, the treatment cost of Hemgenix® depended strongly on assumptions about long-term durability and reimbursement design. The study shows outcome-based annuity reimbursements reduce payers’ treatment-cost exposure under long-term uncertainty, whereas upfront reimbursement minimized the cost of Hemgenix® treatment only with sustained response. However, this cost advantage under partial response was not maintained after applying 3% annual discounting.