FDA-Approved Gene Therapy Beqvez Shows Sustained Efficacy, Safety in Long-Term Hemophilia B Trial

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Long-term safety and efficacy clinical trial data (NCT03307980) for patients with hemophilia B administered the recombinant adeno-associated virus (AAV) vector gene therapy Beqvez (fidanacogene elaparvovec) show sustained factor IX expression, low bleeding rates, and generally favorable safety outcomes. These results, published by The New England Journal of Medicine, demonstrate the potential of Beqvez in providing lasting clinical benefits, despite the need for continued liver monitoring, according to the investigators.^1,2

“The overall safety results suggest that fidanacogene elaparvovec is generally safe,” the study authors wrote. “Asymptomatic liver abnormalities were identified in surveillance ultrasounds, including hepatic steatosis in four participants with overweight and progression to cirrhosis in one participant who had preexisting advanced liver fibrosis associated with iatrogenic hepatitis C virus infection.”¹

Beqvez is a one-time gene therapy that was approved by the FDA in April 2024 to treat adult patients with moderate-to-severe hemophilia B and who currently use factor IX prophylaxis therapy, have a history of severe hemorrhage, or who suffer from frequent serious bleeding episodes with no neutralizing antibodies to the AAV serotype.³ Findings from the Phase III BENEGENE-2 trial (NCT03861273) demonstrated that Beqvez administered at one of the lowest doses for an AAV gene therapy for hemophilia B effectively elevated factor IX levels and significantly lowered bleeding and factor IX consumption.^4,5 The ongoing extended follow-up study lasting up to 15 years after administration of Beqvez will provide additional insight into its efficacy treating hemophilia B.

“Current standard care for hemophilia B is prophylaxis by means of episodic intravenous administration of exogenous factor IX, which leads to peaks and troughs in factor IX levels,” the study authors wrote. “Although effective at reducing bleeding events and slowing long-term joint damage, factor IX replacement requires a high degree of adherence. Recombinant (AAV) vectors provide the opportunity to develop one-time disease-altering therapies for inherited monogenic disorders, including hemophilia.”¹

Trial Design

The 12-month study included 15 patients with severe or moderately severe hemophilia B (factor IX coagulant activity, ≤2% of the normal value). Patients were administered Beqvez at a dose of 5×10¹¹ vector genomes per kilogram of body weight. Patients were then allowed to enroll in a five-year follow-up study. The trial’s safety endpoints included adverse events (AEs) and changes in laboratory measures, while efficacy endpoints included annualized bleeding rate and factor IX activity.

Among 14 participants who completed at least three years of follow-up (median, 5.5; range 3 to 6), eight were still participating at the data cutoff date. None of these patients experienced treatment-related AEs after one year.

During the follow-up period, four patients reported a combined nine serious AEs, none of which were thrombotic or related to treatment with Beqvez and no factor IX inhibitors were detected. Further, mean factor IX activity was in the mild hemophilia range during the follow-up, with a mean annualized bleeding rate of less than one.

Ten patients did not experience a bleeding episode that required treatment. Surveillance liver ultrasounds through one year and up did not show evidence of cancer, but investigators did observe steatosis in four patients who gained weight and had elevated aminotransferase levels.

“Among the 14 participants followed for more than 1 year, the therapy led to a sustained clinical response and generally no or low-grade adverse events, which suggests possible long-term clinical benefit with fidanacogene elaparvovec,” the study authors concluded. “In addition, this study supports the in vivo hemostatic efficacy of FIX-R338L. A phase 3 study of fidanacogene elaparvovec of up to 6 years’ duration is ongoing.”¹

References

1. Rasko J., et al. Fidanacogene Elaparvovec for Hemophilia B — A Multiyear Follow-up Study. N Engl J Med 2025;392:1508-1517 doi/full/10.1056/NEJMoa2307159. VOL. 392 NO. 15.

2. Long-term Safety and Efficacy Study and Dose-Escalation Substudy of PF 06838435 in Individuals With Hemophilia B. ClinicalTrials.gov. Updated October 8, 2024. Accessed April 17, 2025. https://clinicaltrials.gov/study/NCT03307980

3. U.S. FDA Approves Pfizer’s BEQVEZ™ (fidanacogene elaparvovec-dzkt), a One-Time Gene Therapy for Adults with Hemophilia B. Pfizer. April 26, 2024. Accessed April 17, 2025. https://www.pfizer.com/news/press-release/press-release-detail/us-fda-approves-pfizers-beqveztm-fidanacogene-elaparvovec

4. Cuker A, et al. Gene Therapy with Fidanacogene Elaparvovec in Adults with Hemophilia B. Published September 25, 2024. N Engl J Med 2024;391:1108-1118. DOI: 10.1056/NEJMoa2302982. Vol. 391 No. 12.

5. 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. Updated August 23, 2024. Accessed April 17, 2025.