Don Tracy, Associate Editor

Beqvez, a one-time gene therapy, offers hope to patients with moderate to severe hemophilia B who use regular factor IX prophylaxis, suffer severe hemorrhages, or recurrent serious bleeding.Pfizer announced that the FDA has approved Beqvez (fidanacogene elaparvovec-dzkt) as a one-time gene therapy for adults with moderate to severe hemophilia B. The therapy is indicated for patients who currently use factor IX (FIX) prophylaxis therapy, have a history of severe hemorrhage, or experience frequent serious bleeding with no neutralizing antibodies to the adeno-associated virus serotype. In clinical trials, Beqvez was found to help patients to produce their own FIX, lowering the need for regular intravenous (IV) infusions.
The approval was based on promising data from the Phase III open-label, single-arm BENEGENE-2 trial, which evaluated the efficacy and safety of Beqvez in 45 males aged 18 to 65 years with moderately severe to severe hemophilia B. All participants were required to have completed a minimum of six months routine FIX prophylaxis therapy during the lead-in study, also while receiving a single IV infusion of the therapy. Pfizer reported that the primary endpoint of non-inferiority was met, with bleeds no longer present in 60% of patients treated with Beqvez compared to 29% with prophylaxis. While it was well tolerated, a common adverse effect was an increase in transaminases.1
“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, MS, director, Penn Comprehensive and Hemophilia Thrombosis Program, in a press release. “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.”
According to the National Organization for Rare Disorders (NORD), hemophilia B affects one in 25,000 males at birth, with many female carriers not experiencing any symptoms. However, around 10%-25% are expected to develop mild symptoms. Severe symptoms are usually discovered after birth, moderate symptoms around the ages of five or six years, and mild symptoms typically manifesting much later in life.2
“Hemophilia B is caused by a change (variant or mutation) in the F9 gene. The F9 gene is located on the X chromosome and thus is inherited in an X-linked recessive pattern. In about 30% of cases of hemophilia B, the altered gene occurs spontaneously without a previous family history,” reports NORD. “The F9 gene contains instructions for creating the factor IX protein. Variants in the F9 gene can lead to deficient levels of functional factor IX protein. The bleeding symptoms associated with hemophilia B occur due to this deficiency.”
Hemophilia B is classified as a rare genetic bleeding disorder that prevents normal blood clotting due to deficiencies in FIX that cause longer bleeding periods. Currently, the top treatment is prophylactic infusions of FIX replacement therapy, which is only a temporary solution. According to data Pfizer displayed from the World Federation of Hemophilia, more than 38,000 people live with hemophilia B globally.1
“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, EVP, Pfizer, in the press release. “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.”