FDA Approves Pfizer’s Gene Therapy for Adults with Hemophilia B

The FDA has approved Pfizer's one-time gene therapy, Beqvez (fidanacogene elaparvovec-dzkt), for adults with moderate to severe hemophilia B who use factor IX (FIX) prophylaxis therapy, have life-threatening hemorrhages, or experience repeated serious spontaneous bleeding and do not have neutralizing antibodies to adeno-associated virus serotype Rh74var (AAVRh74var) capsid. Beqvez (fidanacogene elaparvovec-dzkt) helps patients produce FIX themselves, therefore avoiding regular intravenous FIX infusions.

Beqvez, an adeno-associated virus-based gene therapy, introduces a functional copy of the FIX gene encoding a high-activity variant of FIX into the transduced cells. According to Pfizer, Beqvez reduced bleeds post-treatment with a median of zero bleeds after three years.

The approval was based on results from the Phase 3 open-label, single-arm study, BENEGENE-2 (NCT03861273). The study evaluated the efficacy and safety of Beqvez in 45 adult males, age 18 to 65, with FIX circulating activity of 2% or less, to evaluate the annualized bleeding rate (ABR) for study participants compared with the usual standard of care. According to Pfizer, “BENEGENE-2 met its primary end point of non-inferiority in the ABR of total bleeds post-Beqvez infusion versus prophylaxis regimen with FIX, administered as part of usual care. A mean ABR of 2.5 was observed among patients who received Beqvez in the efficacy evaluation period—defined as between week 12 and data cutoff (median 1.8 years of follow-up)—after receiving the one-time dose compared to a mean ABR of 4.5 during the lead-in pre-treatment period of at least six months (median 1.2 years of follow-up). Bleeds were eliminated in 60% of patients​​ compared to 29% in the prophylaxis arm. A median ABR of zero (range of 0 to 19) was observed during the efficacy evaluation period compared to the prophylaxis arm in which a median ABR of 1.3 (range of 0 to 53.9) was observed,” (1). In addition, patients were followed for six years in a Phase 1/2a study and a Phase 2a long-term follow up study.

In people with hemophilia B, a deficiency in FIX prevents blood clotting and causes those with the genetic disorder to bleed more often and longer than others. Approximately 38,000 people worldwide live with the disorder (1). People with hemophilia B are at risk of spontaneous bleeding, even with preventive treatment and the standard of care, which includes regular infusions.

“This milestone is a testament to Pfizer’s continued effort to advance the standard of care for people living with hemophilia, with the delivery of a medicine that has the potential to offer both long-term bleed protection and value to the healthcare system because of its one-time administration,” said Aamir Malik, chief US commercial officer and executive vice president, Pfizer, in a press release (1). “We are leveraging our expertise that comes with more than 40 years of experience in the hemophilia space, and are proactively working with treatment centers, payers, and the hemophilia community to appropriately help ensure the healthcare system is prepared to readily deliver Beqvez to the patients who can benefit from it.”

“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,” said Kim Phelan, chief operating officer, The Coalition for Hemophilia B (1). “We are excited to have Beqvez as a promising treatment option for eligible people living with hemophilia B."

The first FDA-approved gene therapy for Pfizer, Beqvez comes to market on the heels of its competitor Hemgenix (etranacogene dezaparvovec-drlb; uniQure/ CSL), which was approved back in November 2022 (2). The pair of hemophilia B gene therapies are priced the same, at $3.5 million per dose. Pfizer said their drug will be available for patients later this quarter. Uniquely, Pfizer is offering what it's calling a warranty program to ensure durability of patient response. This, the company said, is meant to boost payer confidence and ensure better access to the drug for eligible patients.

The European Medicines Agency is also reviewing Beqvez for possible approval in Europe. Regulatory approval in Canada was granted by Health Canada in January 2024 (3). “The Canadian Hemophilia Society welcomes the approval of Beqvez, the second gene therapy for hemophilia B to receive its Notice of Compliance from Health Canada in recent months,” said Wendy Quinn, Canadian Hemophilia Society (CHS) president, in a press release. "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.”

References

1. Pfizer. US FDA Approves Pfizer’s Beqvez (fidanacogene elaparvovec-dzkt), a One-Time Gene Therapy for Adults with Hemophilia B. Press Release. April 26, 2024. https://www.pfizer.com/news/press-release/press-release-detail/us-fda-approves-pfizers-beqveztm-fidanacogene-elaparvovec
2. uniQure. uniQure announces FDA approval of first gene therapy for adults with hemophilia B. Press release. November 22, 2022. https://www.globenewswire.com/news-release/2022/11/22/2561267/0/en/uniQure-announces-FDA-approval-of-first-gene-therapy-for-adults-with-hemophilia-B.html
3. Pfizer Canada. Health Canada Approves Pfizer Canada’s Gene Therapy in Hemophilia B. Press Release. Jan. 3, 2024. https://www.pfizer.ca/en/media-centre/health-canada-approves-pfizer-canadas-gene-therapy-in-hemophilia-b