Gene-ius at work: Hemophilia B treatment enters a new era.

Abstract

Purpose: Hemophilia B is a rare, hereditary bleeding disorder characterized by a deficiency in clotting factor IX (FIX). Traditional therapeutic strategies involve an economically and physically burdensome combination of prophylactic and episodic (ie, on-demand) administration of clotting factor concentrates (CFCs). The first gene therapy for hemophilia B, etranacogene dezaparvovec (Hemgenix), was approved by the Food and Drug Administration (FDA) in November 2022, with approval for fidanacogene elaparvovec (Beqvez) following in April 2024, produced by CSL Behring and Pfizer, respectively. This literature review aims to provide an overview of current therapeutic strategies for the treatment of hemophilia B, introducing and focusing on the efficacy and safety of the novel gene therapies etranacogene dezaparvovec and fidanacogene elaparvovec.

Summary: Both FDA-approved hemophilia B gene therapies, etranacogene dezaparvovec and fidanacogene elaparvovec, utilize adeno-associated virus (AAV) vectors for delivery of the gene encoding FIX. Each of these medications has a distinct AAV serotype, but they have the same treatment modality, with the goal of curing the disease and reducing or eliminating prophylactic CFC requirements. Despite their different AAV serotypes, both products deliver a functional copy of the gene encoding the Padua variant (variant R338L) of human FIX. Recent clinical trials have demonstrated efficacy in increasing FIX concentrations leading to reduced frequency of spontaneous bleeding episodes; however, safety and response durability remain concerns.

Conclusion: For the first time in history, individuals with hemophilia B have access to potentially curative therapies through gene therapy. Both etranacogene dezaparvovec and fidanacogene elaparvovec offer significant efficacy, reducing the number of bleeding episodes and raising FIX concentrations with a single lifetime administration. While concerns remain regarding long-term safety and durability, these therapies represent a major advancement in reducing treatment burden and improving quality of life for patients. The future of hemophilia B management now holds the promise of greater independence from frequent prophylactic treatments.