FDA OKs Second Gene Therapy for Hemophilia B

The FDA has approved a second gene therapy for adults with hemophilia B, drugmaker Pfizer announced on Friday.

The approval of fidanacogene elaparvovec (Beqvez) stipulates use in adult men with moderate to severe hemophilia B, according to Pfizer's statement. Specifically, the approval limits use to patients currently treated with prophylactic factor IX, who have a history of life-threatening hemorrhage, or who have repeated serious spontaneous bleeding episodes, and who do not have neutralizing antibodies to the adeno-associated virus serotype Rh74var capsid.

The gene therapy enables patients with hemophilia B to produce factor IX, rather than treat the condition with intravenous infusions of the blood factor.

"Many people with hemophilia B struggle with the commitment and lifestyle disruption of regular factor IX infusions, as well as spontaneous bleeding episodes, which can lead to painful joint damage and mobility issues," said Adam Cuker, MD, of the Penn Comprehensive and Hemophilia Thrombosis Program at the University of Pennsylvania in Philadelphia, in the statement. "A one-time treatment with Beqvez has the potential to be transformative for appropriate patients by reducing both the medical and treatment burden over time."

Fidanacogene elaparvovec becomes the second approved gene therapy for hemophilia B, following approval of etranacogene dezaparvovec (Hemgenix) in November 2022.

Support for the fidanacogene elaparvovec approval came from the phase III, single-arm, open-label BENEGENE-2 trial involving 45 men with moderate or severe hemophilia B (factor IX circulating activity ≤2%). The primary objective was to compare the annualized bleeding rate (ABR) with the gene therapy versus standard prophylactic factor IX.

From week 12 to data cutoff after 1.8 years of follow-up, ABR decreased from 4.5 during the lead-in period to 2.5 following a single administration of the gene therapy. Bleeds were eliminated in 60% of patients with fidanacogene elaparvovec as compared with 29% with prophylactic factor IX.

The most common (≥5% of patients) adverse event (AE) in phase II/III trials was increased liver enzymes. No deaths, serious AEs, thrombotic events, or use of factor IX inhibitors were reported.

Follow-up will last for a total of 15 years, comprising 6 years in the BENEGENE-2 trial and an additional 9 years during a separate phase III trial to learn about the long-term safety and efficacy of the gene therapy.

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