FDA Approves Fidanacogene Elaparvovec-dzkt as One-Time Gene Therapy for Adults With Hemophilia B


The 1-time treatment may be a better alternative for patients who don’t want to undergo frequent doses of standard of care intravenous factor IX infusions.

Researcher in lab gene therapy -- Image credit: RFBSIP | stock.adobe.com

Image credit: RFBSIP | stock.adobe.com

About the Trial

Trial Name: A Study to Evaluate the Efficacy and Safety of Factor IX Gene Therapy With PF-06838435 in Adult Males With Moderately Severe to Severe Hemophilia B (BENEGENE-2)

ClinicalTrials.gov ID: NCT03861273

Sponsor: Pfizer

Completion Date (Estimated): July 4, 2030

The FDA approved fidanacogene elaparvovec-dzkt (Beqvez; Pfizer) for the treatment of adults with moderate to severe hemophilia B who use factor IX (FIX) prophylaxis therapy, have current or historical life-threatening hemorrhage, or have repeated serious spontaneous bleeding episodes. The approval is based on the results from the phase 3 clinical trial, BENEGENE-2 (NCT03861273).1

Fidanacogene elaparvovec is an adeno-associated virus (AAV)-based gene therapy that introduces a functional copy of the FIX gene in transduced cells, encoding a high-activity FIX variant. Prior to treatment, patients need to undergo a test to check for neutralizing antibodies to adeno-associated virus serotype (AAVRh74var) capsid, and test results will determine whether patients are eligible to receive fidanacogene elaparvovec. The gene therapy is a 1-time treatment that enables people with hemophilia B to produce FIX themselves, as opposed to the current standard of care treatment which requires regular intravenous (IV) infusions of FIX that can be administered as frequently as multiple times per month to multiple times per week.1

“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,” said Adam Cuker, MD, MS, director, Penn Comprehensive and Hemophilia Thrombosis Program, in a press release. “A 1-time treatment with [fidanacogene elaparvovec] has the potential to be transformative for appropriate patients by reducing both the medical and treatment burden over the long term.”1

BENEGENE-2 is an open-label, single-arm phase 3 trial that evaluated the safety and efficacy of fidanacogene elaparvovec in adult male patients aged 18 to 65 years of age with moderately severe to severe hemophilia B. The investigators evaluated the annualized bleeding rate (ABR) for participants who were treated with the gene therapy compared with FIX prophylaxis replacement regimen, administered as part of usual care.1

First, eligible study participants were required to complete a minimum of 6 months of routine FIX prophylaxis therapy in a lead-in study (NCT03587116). Patients received a single IV infusion of fidanacogene elaparvovec (dose equivalent to 5 x 1011 vg/kg of patient’s body weight). To further evaluated the long-term safety and efficacy of fidanacogene elaparvovec, the enrolled patients will be followed for a total of 15 years: 6 years in the BENEGENE-2 study, and an additional 9 years as part of a separate phase 3 trial (NCT05568719).1,2

According to the investigators, the BENEGENE-2 trial met its primary end point of non-inferiority and superiority in the ABR total bleeds. In addition, key secondary end points demonstrated that fidanacogene elaparvovec reduced both ABR and annualized infusion rate by approximately 78% and 92%, respectively. The mean ABR decreased to 1.3 in 12 months, with the mean ABR with fidanacogene elaparvovec being more than 3 times less than the mean ABR during lead-in treatment with FIX prophylaxis therapy, which was 4.43. Further, after 15 months, the mean FIX activity was increased by a substantial amount compared with the pre-specified threshold (27% vs 5%).1,2

The most common adverse events (AEs) reported by patients in phase 3 and 1/2 clinical studies was an increase in transaminases, which occurred in 26 of 60 patients treated at the recommended dose, and 31 of 60 patients received corticosteroids. Additionally, in phase 1 and 2 trials, some serious AEs related to treatment were duodenal ulcer hemorrhage and an increase in immune-mediated liver aminotransferase levels. Overall, fidanacogene elaparvovec was well-tolerated in patients, with no deaths, serious AEs related to treatment or associated infusion reactions, thrombotic events, or FIX inhibitors reported in BENEGENE-2.1,2

“For people living with hemophilia, disease management can interfere with many aspects of their lives. A 1-time infusion of [fidanacogene elaparvovec] may allow eligible patients more time for the things they love,” said Kim Phelan, COO, The Coalition for Hemophilia B, in the press release. “We are excited to have [fidanacogene elaparvovec] 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.”1


1. Pfizer. U.S. FDA Approves Pfizer’s BEQVEZ™ (fidanacogene elaparvovec-dzkt), a One-Time Gene Therapy for Adults with Hemophilia B. News release. April 26, 2024. Accessed April 30, 2024. https://www.pfizer.com/news/press-release/press-release-detail/us-fda-approves-pfizers-beqveztm-fidanacogene-elaparvovec
2. Hunter, E. Hemophilia B Gene Therapy Significantly Reduces Annual Bleeds in Phase 3 Trial. Pharmacy Times. January 4, 2023. Accessed April 30, 2024. https://www.pharmacytimes.com/view/hemophilia-b-gene-therapy-significantly-reduces-annual-bleeds-in-phase-3-trial
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