FDA Accepts BLA Filing for Hemophilia B Gene Therapy Fidanacogene Elaparvovec


In addition to the BLA acceptance, Pfizer noted that a European MAA for the gene therapy has been accepted by the EMA.

Pfizer’s biologics license application (BLA) for fidanacogene elaparvovec, an investigational adeno-associated virus (AAV) vector-based gene therapy intended to treat adult patients with hemophilia B, has been accepted by the FDA for filing with a Prescription Drug User Fee Act (PDUFA) date set for Q2 2024.1

In addition to the BLA acceptance, Pfizer noted that a European marketing authorization application (MAA) for the gene therapy has been accepted by the European Medicines Agency. Both the BLA and the MAA are supported by data from the phase 3 BENEGENE-2 clinical trial (NCT03861273) that assessed fidanacogene elaparvovec against the standard of care (SOC) Factor IX (FIX) prophylaxis replacement regimen in 45 patients with hemophilia B. Patients enrolled in BENEGENE-2 were first evaluated in a separate lead in study (NCT03587116) that assessed their annualized bleeding rates (ABR) on SOC therapy for a period of at least 6 months. An ABR of 4.43 for the lead in study was reported.2

In BENEGENE-2, the patients received treatment with fidanacogene elaparvovec at a dose of 5x1011 vg/kg. Fidanacogene elaparvovec was assessed as superior to SOC, with a mean ABR for all bleeds of 1.3 for the period of 12 months from 12 weeks posttreatment to 15 months posttreatment, a 71% reduction from the lead in study ABR (P <.0001). In terms of safety, Pfizer reported that the gene therapy was well-tolerated in BENEGENE-2. There were 14 serious adverse events (SAEs) observed among 7 patients in the trial. Two of the SAEs, which occurred in a single patient, were deemed related to the treatment. These included a duodenal ulcer hemorrhage and anemia during corticosteroid use.

“Gene therapy marks a new era of scientific advancement, and if approved, we believe fidanacogene elaparvovec has the potential to transform the lives of people living with hemophilia B who are eligible for treatment,” Chris Boshoff, MD, PhD, chief development officer, oncology and rare disease, Pfizer Global Product Development, said in a statement.1 “We look forward to continuing to work with global regulatory authorities to bring this innovative potential treatment to patients as quickly as possible. Patients are at the center of our legacy of innovation in hemophilia. Despite significant progress in their treatment, those living with hemophilia continue to experience disruption to daily life and need new options.”

Fidanacogene elaparvovec consists of a high-activity variant of the human coagulation FIX gene delivered via an AAV capsid.1 It is intended to allow the body to produce FIX continuously after a single dose. The news follows the first FDA approval of a gene therapy for treating hemophilia B in November 2022, when UniQure and CSL Behring’s etranacogene dezaparvovec (EtranaDez), marketed as Hemgenix, was approved by the FDA for adults with hemophilia B who currently use FIX prophylaxis therapy, have current or historical life-threatening hemorrhage, or have repeated, serious spontaneous bleeding episodes.3 EtranaDez was also assessed as superior to SOC in terms of ABR in the phase 3 HOPE-B trial (NCT03569891); a study published in the New England Journal of Medicine in February 2023 reported that the ABR decreased from 4.19 (95% CI, 3.22-5.45) to 1.51 (95% CI, 0.81-2.82) during months 7 to 18 posttreatment, for a rate ratio of 0.36 (95% Wald CI, 0.20-0.64; P <.001).4

Progress in gene therapy for hemophilia A has also been advancing recently. Notably, Biomarin’s valoctocogene roxaparvovec (val-rox; Roctavian) for the treatment of severe hemophilia A has a PDUFA date set for June 30, 2023.5 The current PDUFA date is the result of an extension from an earlier PDUFA date set for March 31, 2023, made in relation to the submission of a 3-year data analysis from the ongoing GENEr8-1 clinical trial (NCT03370913). Biomarin previously received conditional marketing authorization for val-rox from the European Commission in August 2022.

1. FDA accepts Pfizer’s application for hemophilia B gene therapy fidanacogene elaparvovec. News release. Pfizer Inc. June 27, 2023. Accessed June 27, 2023. https://www.pfizer.com/news/press-release/press-release-detail/fda-accepts-pfizers-application-hemophilia-b-gene-therapy
2. Pfizer announces positive top-line results from phase 3 study of hemophilia B gene therapy candidate. News release. Pfizer Inc. December 29, 2022. Accessed June 27, 2023. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-announces-positive-top-line-results-phase-3-study
3. FDA approves first gene therapy to treat adults with hemophilia B. News release. FDA. November 22, 2022. Accessed June 27, 2023.https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-treat-adults-hemophilia-b
4. Pipe SW, Leebeek WGF, Recht M, et al. Gene Therapy with Etranacogene Dezaparvovec for Hemophilia B. N Engl J Med. 2023; 388:706-718. doi:10.1056/NEJMoa2211644
5. BioMarin provides update on FDA review of Roctavian (Valoctocogene Roxaparvovec) gene therapy for adults with severe hemophilia A. News release. Biomarin. March 6, 2023. Accessed June 27, 2023.https://investors.biomarin.com/2023-03-06-BioMarin-Provides-Update-on-FDA-Review-of-ROCTAVIAN-TM-Valoctocogene-Roxaparvovec-Gene-Therapy-for-Adults-with-Severe-Hemophilia-A
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