Health Canada has approved Pfizer Canada’s gene therapy fidanacogene elaparvovec under the name Beqvez for treating patients with moderately severe to severe hemophilia B with congenital Factor IX (FIX) deficiency who are negative for neutralizing antibodies to variant adeno-associated virus (AAV) serotype Rh74.1
"Pfizer has more than 30 years of experience in developing and commercializing therapies for hematological disorders, and a deep understanding of the significant challenges that people living with hemophilia continually face," Frédéric Lavoie, Canada Lead – Specialty Business Unit, Pfizer Canada, said in a statement.1 "We are proud to introduce an innovative therapy for people living with hemophilia B in the form of gene therapy."
The approval is based on data from the open label, single arm Phase 3 BENEGENE-2 trial (NCT03861273) which met its primary endpoint of demonstrating non-inferiority and superiority in annualized bleeding rates (ABR) compared with standard of care FIX therapy in 45 enrolled participants. Fidanacogene elaparvovec gene therapy uses a bioengineered AAV capsid to deliver a high activity variant of the human FIX gene.
"Our team at McMaster University is proud to have been a clinical trial site in Canada that studied this therapy," Alfonso Iorio, MD Professor and Chair, Health Research Methods, Evidence, and Impact, McMaster University, added.1 "This new treatment shows potential in reducing the burden of frequent infusions by providing, with a single infusion, a persistent liver production of FIX, which could help improve the life of those affected."
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Topline results from the trial were announced in December 2022, and showed that during the lead-in period, the ABR with standard of care FIX was 4.43 compared with an ABR of 1.3 from week 12 through 15 months with fidanacogen eelaparvovec. This was equivalent to a 71% reduction in ABR, which was significantly superior to standard FIX therapy (P <.0001).2 Moreover, there was a 92% reduction in the annualized infusion rate of exogenous FIX following infusion with fidanacogene elaparvovec (P <.0001), and the safety profile with fidanacogene elaparvovec was consistent with prior reports from the phase 1/2 studies, Pfizer noted. Overall, there were 14 serious adverse events (SAEs) observed in 7 patients (16%), none of which were related to infusion reactions, thrombotic events, or FIX inhibitors.
- Health Canada has granted approval for Pfizer's gene therapy, Beqvez (fidanacogene elaparvovec), for treating patients with moderately severe to severe hemophilia B, showcasing a new approach to managing this congenital Factor IX deficiency.
- Beqvez's approval is based on positive results from the BENEGENE-2 trial, where the gene therapy demonstrated non-inferiority and superiority in annualized bleeding rates compared to standard Factor IX therapy.
- Applications have been accepted and reviews are pending by the FDA and EMA.
"The Canadian Hemophilia Society (CHS) welcomes the approval of BEQVEZ, the second gene therapy for hemophilia B to receive its Notice of Compliance from Health Canada in recent months," Wendy Quinn, president, CHS, added.1 "Our hope is that gene therapy will be made available to those who are eligible and have made an informed decision to proceed. We are committed to ensuring education and support for our community as gene therapies have the potential to fundamentally transform treatment and improve quality of life for some individuals. The CHS will work closely with health authorities in the provinces and territories to ensure that gene therapies for hemophilia B become accessible to eligible patients across Canada as soon as possible."
In the United States, Pfizer is awaiting the FDA’s decision on the biologics license application for fidanacogene elaparvovec, which the FDA accepted for review in June 2023.3 The Prescription Drug User Fee Act (PDUFA) date is currently set for some time in Q2 2024. The European Medicines Agency has also accepted the marketing authorization application for the therapy.
1. Health Canada approves Pfizer Canada's gene therapy in hemophilia B. News release. Pfizer Canada. January 3, 2024. https://www.newswire.ca/news-releases/health-canada-approves-pfizer-canada-s-gene-therapy-in-hemophilia-b-841249479.html
2. Pfizer announces positive top-line results from phase 3 study of hemophilia B gene therapy candidate. News release. Pfizer. December 20, 2022. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-announces-positive-top-line-results-phase-3-study
3. 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