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FDA approves fidanacogene elaparvovec, a one-time gene therapy, for adult patients with hemophilia B

On April 26th, 2024, the U.S. Food and Drug Administration (FDA) granted approval to fidanacogene elaparvovec, a one-time gene therapy, for adult patients with moderate to severe hemophilia B who currently use factor IX (FIX) prophylaxis, have current or historical life-threatening hemorrhage, or have repeated, serious spontaneous bleeding episodes, and do not have neutralizing antibodies to the adeno-associated virus (AAV) serotype Rh74var (AAVRh74var) capsid.1

Hemophilia B is a rare inherited disease predominantly affecting males, in which there is insufficient production of FIX, resulting in abnormal blood clotting and long bleeding episodes.2 Fidanacogene elaparvovec is an AAV-based gene therapy which enables individuals to produce FIX, preventing the need for regular infusions of this clotting factor. The approval of this therapy is based on results from the Phase III BENEGENE-2 trial (NCT03861273), which evaluated the safety and efficacy of fidanacogene elaparvovec in 45 adult males (aged 18-65) with moderate to severe hemophilia B. Patients enrolled in this study had completed a minimum of six months of routine FIX prophylaxis therapy during a lead-in study (NCT03587116) before receiving the gene therapy. The primary endpoint of this trial was the annualized bleeding rate (ABR) following a single dose of fidanacogene elaparvovec compared with standard-of-care (SoC) prophylactic FIX replacement therapy.1

The trial met its primary endpoint, with a mean ABR of 2.5 observed in patients who received fidanacogene elaparvovec in the efficacy evaluation period (median follow-up of 1.8 years) compared to a mean ABR of 4.5 during the lead-in pre-treatment period of at least six months (median follow-up of 1.2 years). Bleeds were eliminated in 60% of patients compared to 29% of patients in the prophylaxis arm, and a median ABR of zero was observed in the gene therapy arm compared to a median ABR of 1.3 in the prophylaxis arm.1

Regarding safety, fidanacogene elaparvovec was well-tolerated in patients, with the most common adverse event (AE) being an increase in transaminases. There were no reports of death, serious treatment-related AEs, infusion reaction-related AEs, thrombotic events, or development of FIX inhibitors. Patients will be followed up for a total of 15 years and monitored for long-term treatment safety and durability.1

At the 2023 ASH Annual Meeting and Exposition, we caught up with Evelien Krumb, MD, UCLouvain Saint-Luc, Brussels, Belgium, who shared her thoughts on how the approval of gene therapies may impact the hemophilia treatment landscape. Dr Krumb highlighted, “I think the approval of gene therapy, in general, for hemophilia is very exciting for the community, both for treaters and for patients. Of course, there are a lot of unanswered questions that still remain, but I think it can give us hope that one day we will be able to have bleed-free patients who are bleed-free throughout their lifetime and who won’t rely on regular administration of treatment.”

With the approval of fidanacogene elaparvovec, it is hoped that patients with hemophilia B will have access to a promising therapeutic option which avoids the need for regular infusions of FIX, subsequently improving patient quality of life (QoL).

References

  1. Pfizer. U.S. FDA Approves Pfizer’s BEQVEZ™ (fidanacogene elaparvovec-dzkt), a One-Time Gene Therapy for Adults with Hemophilia B. Available here. (Last accessed 30/04/2024).
  2. Miller CH. The Clinical Genetics of Hemophilia B (Factor IX Deficiency). The Application of Clinical Genetics. 2021 Nov 23;14:445-454.

Written by Anya Dragojlovic Kerkache