FDA Approves One-Time Gene Therapy Fidanacogene Elaparvovec for Hemophilia B

The FDA has approved Pfizer's fidanacogene elaparvovec-dzkt (Beqvez) for the treatment of moderate to severe hemophilia B currently using prophylactic factor IX (FIX) therapy or have current or past life-threatening hemorrhage or serious bleeding episodes, and who do not have neutralizing antibodies to adeno-associated virus serotype Rh74var (AAVRh74var) capsid, the company announced today.¹

Hemophilia is a rare genetic bleeding disorder characterized by abnormal blood clotting due to FIX deficiency, leading patients to bleed for longer and more frequently than others.² Fidanacogene elaparvovec is a one-time therapy designed to enable those with hemophilia B to produce their own FIX, while the current standard of care entails regular intravenous infusions of FIX multiple times per week or month.^1,3

“Many people with hemophilia B struggle with the commitment and lifestyle disruption of regular FIX infusions, as well as spontaneous bleeding episodes, which can lead to painful joint damage and mobility issues,” Adam Cuker, MD, MS, director of the Penn Comprehensive and Hemophilia Thrombosis Program, said in a statement.¹ “A one-time treatment with Beqvez has the potential to be transformative for appropriate patients by reducing both the medical and treatment burden over the long term.”

FDA Approved | Image credit: chrisdorney - stock.adobe.com

Fidanacogene elaparvovec's approval is based on results from the pivotal phase 3, open-label BENEGENE-2 study (NCT03861273), a single-arm study evaluating the therapy's efficacy and safety in 45 adult male participants aged 18 to 65 years.⁴ The main objective of BENEGENE-2 was to assess the annualized bleeding rate (ABR) for patients treated with a single intravenous dose of fidanacogene elaparvovec compared with standard-of-care prophylactic FIX replacement therapy.¹

Participants in the study had moderately severe to severe hemophilia B, which was defined as circulating FIX activity of 2% or less, and all completed a minimum of 6 months of FIX prophylaxis therapy during a lead-in study before receiving fidanacogene elaparvovec.

The study reached its primary end point, which was gene therapy's non-inferiority to standard prophylactic FIX therapy in terms of the ABR of total bleeds following fidanacogene elaparvovec infusion vs FIX prophylaxis. Patients who received a one-time dose of gene therapy had a mean ABR of 2.5 during the efficacy evaluation period from week 12 of the study to data cutoff, which was a median 1.8 years of follow-up. Those receiving standard FIX prophylaxis had an ABR of 4.5 during the 6-month treatment lead-in period at a median 1.2 years of follow-up.

Further, bleeds were eliminated in 60% of those who received fidanacogene elaparvovec vs 29% when receiving prophylaxis. The median ABR was 0 (range, 0-19) with fidanacogene elaparvovec vs 1.3 (range, 0-53.9) with usual prophylaxis.

Patients participating in the trial will be followed for up to 15 years total, including 6 years for the BENEGENE-2 study and 9 years in a phase 3 study (NCT05568719) on the therapy's long-term safety and efficacy.

Overall, fidanacogene elaparvovec was well-tolerated, with an increase in transaminases being the most common adverse reaction with an incidence of 5% or more in the phase 3 and 1/2 studies. Twenty-six out of 60 patients treated at the recommended dose of fidanacogene elaparvovec showed elevated transaminases, and 31 out of 60 patients received corticosteroids. There were no deaths or serious adverse reactions related to fidanacogene elaparvovec or associated with infusion reactions, thrombotic events, or FIX inhibitors.

Pfizer is launching a warranty program based on the durability of patient responses to the one-time treatment, with the goal of maximizing access for eligible patients, giving payers greater certainty, and insuring against the risk of efficacy failure to offer financial protection, according to the news release.

“For people living with hemophilia, disease management can interfere with many aspects of their lives. A one-time infusion of Beqvez may allow eligible patients more time for the things they love,” Kim Phelan, chief operating officer at The Coalition for Hemophilia B, said.¹ “We are excited to have Beqvez as a promising treatment option for eligible people living with hemophilia B. We look forward to learning more and celebrating with the community and with Pfizer at our annual conference that is currently taking place.”

References

1. U.S. FDA approves Pfizer’s Beqvez (fidanacogene elaparvovec-dzkt), a one-time gene therapy for adults with hemophilia B. News release. Pfizer. April 26, 2024. Accessed April 26, 2024. https://www.businesswire.com/news/home/20240425269649/en/U.S.-FDA-Approves-Pfizer%E2%80%99s-BEQVEZ%E2%84%A2-fidanacogene-elaparvovec-dzkt-a-One-Time-Gene-Therapy-for-Adults-with-Hemophilia-B

2. Hemophilia B. National Organization for Rare Disorders. Updated September 20, 2023. Accessed April 26, 2024. https://rarediseases.org/rare-diseases/hemophilia-b/

3. Hart DP, Matino D, Astermark J, et al. International consensus recommendations on the management of people with haemophilia B. Ther Adv Hematol. Published online April 22, 2022. doi:10.1177/20406207221085202