RARE Daily

FDA Approves Pfizer’s Hemophilia B Gene Therapy

April 26, 2024

Rare Daily Staff

The U.S. Food and Drug Administration approved Pfizer’s Beqvez, a gene therapy for the treatment of the moderate to severe form of the rare, bleeding disorder hemophilia B.

The gene therapy is approved for adults who currently use factor IX (FIX) prophylaxis therapy, or have current or historical life-threatening hemorrhage, or have repeated, serious spontaneous bleeding episodes, and do not have neutralizing antibodies to adeno-associated virus serotype Rh74var capsid as detected by an FDA-approved test.

Hemophilia B is a rare genetic bleeding disorder that prevents normal blood clotting because of a deficiency in FIX that causes those with the disease to bleed more frequently and longer than others. The standard of care for hemophilia B treatment is prophylactic infusions of FIX replacement therapy that temporarily replace or supplement low levels of blood-clotting factor. Despite prophylaxis and regular intravenous infusions, many people living with moderate to severe hemophilia B are at risk of spontaneous bleeding episodes.

The current standard of care also places strain on healthcare systems’ budgets and resource utilization. According to the World Federation of Hemophilia, more than 38,000 people worldwide are living with hemophilia B.

Beqvez is a one-time treatment that is designed to enable people living with hemophilia B to produce FIX themselves rather than the current standard of care, which requires regular intravenous infusions of FIX that are often administered multiple times a week or multiple times a month.

In December 2014, Pfizer licensed Beqvez from Spark Therapeutics. Under the agreement, Pfizer assumed responsibility for pivotal studies, any regulatory activities, and potential global commercialization of this gene therapy. Beqvez is currently under review with the European Medicines Agency (EMA), and the treatment recently received regulatory approval in Canada.

“Many people with hemophilia B struggle with the commitment and lifestyle disruption of regular FIX infusions, as well as spontaneous bleeding episodes, which can lead to painful joint damage and mobility issues,” said Adam Cuker, director of the Penn Comprehensive and Hemophilia Thrombosis Program. “A one-time treatment with Beqvez has the potential to be transformative for appropriate patients by reducing both the medical and treatment burden over the long term.”

In addition to Beqvez, Pfizer currently has two other phase 3 programs investigating gene therapy in populations where there is a high unmet need: hemophilia A and Duchenne muscular dystrophy.

The FDA approval is based on the results from the pivotal BENEGENE-2 study, a phase 3, open-label, single-arm study to evaluate the efficacy and safety of Beqvez in adult male participants (age 18–65) with moderately severe to severe hemophilia B (defined as FIX circulating activity of 2 percent or less). The main objective of the study is to evaluate the annualized bleeding rate (ABR) for participants treated with gene therapy versus FIX prophylaxis replacement regimen, administered as part of usual care.

BENEGENE-2 met its primary endpoint 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 percent of patients​​ compared to 29 percent 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.

Beqvez was generally well-tolerated in patients who received it. The most common adverse reaction (incidence ≥5 percent) reported in phase 3 and 1/2 clinical studies was an increase in transaminases. No deaths, serious adverse events related to treatment or associated with infusion reactions, thrombotic events, or FIX inhibitors were reported. Elevated transaminases were observed in 26 out of 60 patients treated at the recommended dose and 31 out of 60 patients received corticosteroids.

Beqvez patients have been followed up to six years in a phase 1/2a study and its corresponding Phase 2a long-term follow-up study. Pfizer is continuing to monitor long-term treatment durability and safety in its clinical program over the course of 15 years.

Pfizer said it is launching a warranty program based on durability of patient response to treatment. The goal of the warranty is to provide greater certainty to payers, maximize access for eligible patients who receive Beqvez, and offer financial protection by insuring against the risk of efficacy failure.

Aamir Malik, chief U.S. commercial officer and executive vice president of Pfizer said the company is working with treatment centers, payers, and the hemophilia community to “help ensure the healthcare system is prepared to readily deliver Beqvez to the patients who can benefit from it.”

Photo: Aamir Malik, chief U.S. commercial officer and executive vice president of Pfizer 

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