FDA approves Beqvez gene therapy for adults with hemophilia B

Treatment for those on FIX replacement therapy or who have bleeding episodes

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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The U.S. Food and Drug Administration (FDA) has approved the one-time gene therapy fidanacogene elaparvovec for treating certain adults with moderate to severe hemophilia B.

The therapy will be sold under the name Beqvez as it is in Canada, where it was approved for a similar indication this year. Marketed by Pfizer, Beqvez is under review in the European Union. It’s now the second approved gene therapy for hemophilia B in the U.S., following the clearance of Hemgenix in 2022 for certain adults with hemophilia B.

“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,” Aamir Malik, Pfizer’s chief U.S. commercial officer and executive vice president, said in a company press release.

Beqvez is indicated for patients who are on prophylactic, or preventive, treatment with a factor IX (FIX) replacement therapy or are having or had life-threatening bleeding episodes, or repeated serious spontaneous bleeds.

To be eligible for treatment, patients must not have preexisting neutralizing antibodies against the adeno-associated virus serotype Rh74var (AAVRh74var) capsid, the outer shell of the therapy’s delivery virus, as detected by an FDA-approved companion diagnostic test.

The therapy also shouldn’t be administered to those who test positive for neutralizing antibodies against FIX (FIX inhibitors), who show signs of HIV infection, who are allergic to FIX replacement therapies, or who have certain liver diseases, according to its label. Patients will have blood and liver function tests to rule out these factors before treatment.

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Rollout of Beqvez, and how it benefits hemophilia B patients

Pfizer is launching a warranty program for Beqvez based on the durability of patients’ response to treatment that seeks to both maximize’ access to the therapy and offer financial protection by providing insurance against the risk of its failure. The company is also offering personalized patient support services for hemophilia B patients who are prescribed Beqvez through the Pfizer Gene Together program.

“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,” Malik said.

In hemophilia B, mutations in the F9 gene mean the body doesn’t have enough FIX, a blood clotting protein.

Standard of care for hemophilia B has historically involved administering regular infusions into the bloodstream of lab-made or human blood-derived FIX to prevent and control the excessive and prolonged bleeding episodes that mark the disease. Many patients with moderate to severe hemophilia B are still at risk of spontaneous bleeding even with these therapies, which pose a significant burden to both patients and healthcare systems.

Formerly SPK-9001, Beqvez delivers a functional version of the F9 gene to liver cells, enabling them to continuously produce their own FIX. The specific version of the F9 gene delivered by the therapy encodes a high-activity FIX variant called FIX-R338L.

How is Beqvez administered?

The gene therapy is infused into the bloodstream after being packaged into a viral carrier that helps it be taken up by patients’ cells. It uses a recombinant, or lab-made, viral capsid (AAVRh74var) derived from a natural form of the virus AAVRh74 that’s not known to cause disease in humans.

Beqvez should be administered via a single infusion into the vein at a recommended dose of 5×1011 vector genomes per kg (vg/kg) of body weight in hospitals and clinical centers under the supervision of a physician who’s experienced in treating hemophilia.

“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, MD, 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.”

“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 of The Coalition for Hemophilia B.

Beqvez’s approval is based largely on data from the open-label Phase 3 BENEGENE-2 clinical trial (NCT03861273) that tested the effects of the therapy, which was given as a single infusion into the vein at a dose of 5×1011 vg/kg, in men, ages 18-65, with moderate to severe hemophilia B.

BENEGENE-2 enrolled 45 patients. From these, 41 were followed for at least 15 months after receiving the infusion. The median follow-up period for the 45 treated patients was two years after the infusion.

The patients’ mean annualized bleeding rates dropped to 2.5 bleeds a year after Beqvez treatment compared with 4.5 bleeds a year with prophylactic FIX replacement therapy for at least six months in an earlier lead-in study (NCT03587116).

The median annualized bleeding rate also dropped from 1.3 bleeds a year during the lead-in study to 0 in the period after treatment with Beqvez. Also, more than half the patients (60%) had no bleeds after receiving Beqvez, while less than a third (29%) achieved the same outcome during the lead-in study.

Beqvez was found to be generally well tolerated. The most common side effect reported in clinical trials was an increase in the levels of certain liver enzymes. No deaths, blood clot-related events, serious treatment-related side effects, or cases of FIX inhibitors were reported.

Participants will be followed for up to 15 years, including six years in the ongoing BENEGENE-2 study and nine more in a long-term Phase 3 extension study (NCT05568719) with the goal being to assess Beqvez’s long-term safety and efficacy.