Cost-effectiveness of gene therapy with etranacogene dezaparvovec versus factor IX prophylaxis in men with hemophilia B in Brazil

Authors: Ana Clara Silva Mendes¹, Ricardo Mesquita Camelo², Augusto Afonso Guerra Júnior¹, Francisco de Assis Acurcio³

Published: 31 January 2025

Open Access

Abstract

Hemophilia B (HB) is a hereditary coagulopathy caused by mutations in the FIX gene on the X chromosome, which encodes coagulation factor IX (FIX). Globally, an estimated 33,385 individuals live with hemophilia B, including 2,227 in Brazil. Reduced residual plasma FIX activity elevates the risk of spontaneous bleeding, particularly hemarthrosis, which can lead to hemophilic arthropathy, reduced mobility, and impaired quality of life.

Standard treatment for hemophilia B involves intravenous replacement of exogenous FIX to prevent or manage bleeding episodes. Prophylaxis is the globally recommended approach to mitigate bleeds and associated complications. In Brazil, prophylaxis was incorporated into the SUS in 2012, and the cost of FIX concentrates and infusion products has been a barrier to access for patients.

We evaluated the cost-effectiveness of etranacogene dezaparvovec, a gene therapy for hemophilia B, compared to standard prophylaxis with pdFIX in Brazil. The analysis was conducted from the perspective of the Brazilian public health system (SUS) and included direct medical costs related to treatment and management of hemophilia B.

Keywords: hemophilia B, gene therapy, cost-effectiveness, Brazil, etranacogene dezaparvovec

Introduction

Hemophilia B (HB) is a hereditary coagulopathy caused by mutations in the FIX gene on the X chromosome, which encodes coagulation factor IX (FIX). Globally, an estimated 33,385 individuals live with hemophilia B, including 2,227 in Brazil. Reduced residual plasma FIX activity elevates the risk of spontaneous bleeding, particularly hemarthrosis, which can lead to hemophilic arthropathy, reduced mobility, and impaired quality of life.

Standard treatment for hemophilia B involves intravenous replacement of exogenous FIX to prevent or manage bleeding episodes. Prophylaxis is the globally recommended approach to mitigate bleeds and associated complications. In Brazil, prophylaxis was incorporated into the SUS in 2012, and the cost of FIX concentrates and infusion products has been a barrier to access for patients.

The costs for people with hemophilia B treatment with etranacogene dezaparvovec include the price of the drug and the hepatic monitoring exams. For therapy with etranacogene dezaparvovec, a 40% reduction in its launch price was observed prior to commercialization in Brazil. Similarly, the etranacogene dezaparvovec launch price of US$ 3.5 million was reduced, yielding a model-based medication cost of US$ 2.1 million.

The costs included hepatic monitoring tests for aspartate aminotransferase (AST) and alanine aminotransferase (ALT), performed weekly for three months following infusion. For patients treated with etranacogene dezaparvovec, the monitoring costs were estimated based on the duration of maximum bleeding reduction after treatment.

Methods

We conducted a cost-effectiveness analysis to compare etranacogene dezaparvovec and pdFIX prophylaxis. The analysis was performed using a decision-analytic model to estimate the costs and outcomes associated with each treatment strategy.

Results

The incremental cost-effectiveness ratio (ICER) was calculated for both treatment strategies. The ICER represented the cost per additional event-free year gained with etranacogene dezaparvovec compared to pdFIX prophylaxis.

Extending the time horizon to 20 years reduced the ICER to US$ 34,400 (BRL 172,000) per bleeding event avoided. This reduction came at a minimal impact on bleeding rates.

Discussion

Health Technology Assessment (HTA) is a systematic process that evaluates the properties, effects, and impacts of health technologies. The primary goal of HTA is to inform decision-making in healthcare by assessing the medical, social, economic, and ethical implications of the use of health technologies, including their clinical effectiveness, safety, cost-effectiveness, and budget impact.

Another key short-term side effect, drug-induced hepatitis, is believed to result from a cytotoxic immune response to the AAV capsid. All AAV vector-based gene therapy trials for people with hemophilia B reported some degree of asymptomatic hepatotoxicity. In certain cases, this was accompanied by a decline in FIX activity, which might or might not respond to immunomodulation with corticosteroids.

Conclusion

In conclusion, etranacogene dezaparvovec presents a cost-effective alternative to standard prophylaxis with pdFIX for men with hemophilia B in Brazil. The analysis suggests that the long-term benefits of gene therapy may outweigh the initial costs, providing a sustainable solution for managing hemophilia B in the public health system.

Conflict of Interest

RMC declared financial support as a speaker and to participate in scientific events from Bayer, NovoNordisk, Hoffman-La Roche, and Takeda, all unrelated to this study. JAT, ACSM, MAJ, and FAA, declare that there are no conflicts of interest that could influence these results.

Funding Statement

The study did not receive financial support for its preparation, development, or publication.

Acknowledgements

We thank the CCACTES/UFMG team – Collaborating Center of Research, Development, and Excellence in Health, for their support.

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