Pfizer Inc. (NYSE: PFE) today announced that the European Commission (EC) has granted conditional marketing authorization for DURVEQTIX® (fidanacogene elaparvovec), a gene therapy for the treatment of severe and moderately severe hemophilia B (congenital factor IX deficiency) in adult patients without a history of factor IX inhibitors and without detectable antibodies to variant AAV serotype Rh74. DURVEQTIX is designed to enable people living with hemophilia B to produce factor IX (FIX) themselves via a one-time dose, rather than multiple intravenous FIX infusions weekly or biweekly with the current standard of care.1,2,3
"There is a substantial medical and treatment burden for people with hemophilia B that receive standard of care today, with frequent infusions and many remaining at risk of breakthrough bleeds that can lead to pain and restricted mobility," said Alexandre de Germay, Chief International Commercial Officer and Executive Vice President, Pfizer. "DURVEQTIX has shown the potential to offer long-term bleed protection in a one-time dose, reducing or eliminating bleeds for the appropriate patients with hemophilia B. These outcomes and their impact could become potentially transformative for hemophilia B care in the European Union."
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.1,4 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.1,2 Despite prophylaxis and regular intravenous infusions, many people living with moderate to severe hemophilia B are at risk of spontaneous bleeding episodes.5,6,7 The current standard of care also places strain on healthcare systems' budgets and resource utilization.6,8,9,10 According to the World Federation of Hemophilia, more than 42,000 people worldwide are living with hemophilia B.11
The conditional marketing authorization is based on results from the pivotal Phase 3 BENEGENE-2 study (NCT03861273) evaluating the efficacy and safety of DURVEQTIX in adult male participants (age 18-62) with moderately severe to severe hemophilia B. BENEGENE-2 met its primary efficacy endpoint of non-inferiority and demonstrated a statistically significant decrease in annualized bleeding rate (ABR) for total bleeds (treated and untreated) post-DURVEQTIX infusion versus prophylaxis regimen with FIX, administered as part of usual care. Efficacy, based on ABR, also remained stable during year two to year four after treatment. DURVEQTIX was generally well-tolerated, with a safety profile consistent with Phase 1/2 results.
This conditional marketing authorization is valid in all 27 European Union (EU) member states, as well as in Iceland, Liechtenstein, and Norway. The EC approval follows recent regulatory approvals by the U.S. Food and Drug Administration (FDA) and Health Canada, where it is marketed as BEQVEZTM.
This milestone builds on Pfizer's more than 40-year commitment to delivering breakthrough solutions to improve the lives of people living with hemophilia. In addition to DURVEQTIX, Pfizer recently reported positive results from a Phase 3 program investigating a gene therapy in hemophilia A (giroctocogene fitelparvovec). Additionally, a Phase 3 trial is investigating marstacimab, a novel, investigational, anti-tissue factor pathway inhibitor for the treatment of people with hemophilia A and B with and without inhibitors. A Biologics License Application and European Marketing Authorization Application for marstacimab for eligible patients without inhibitors are currently under review with the FDA and European Medicines Agency (EMA), respectively.
About DURVEQTIX® (fidanacogene elaparvovec)
DURVEQTIX is a gene therapy that contains a bio-engineered adeno-associated virus (AAV) capsid and a high-activity variant of human coagulation FIX gene. For people living with hemophilia B, the goal of this gene therapy is to enable them to produce FIX themselves via this one-time treatment rather than needing regular intravenous infusions of FIX, as is the current standard of care.1,2,3
In December 2014, Pfizer licensed DURVEQTIX from Spark® Therapeutics. Under the agreement, Pfizer assumed responsibility for pivotal studies, any regulatory activities, and potential global commercialization of this gene therapy.
About BENEGENE-2
The BENEGENE-2 study is a Phase 3, open-label, single-arm study to evaluate the efficacy and safety of DURVEQTIX in adult male participants (age 18-65) with moderately severe to severe hemophilia B (defined as FIX circulating activity of 2% or less). The main objective of the study is to evaluate the ABR for participants treated with gene therapy versus FIX prophylaxis replacement regimen, administered as part of usual care.
The study enrolled and dosed 45 participants. Eligible study participants have completed a minimum six months of routine FIX prophylaxis therapy during the lead-in study (NCT03587116) and received one intravenous dose of DURVEQTIX at a dose of 5 x 1011 vg/kg. Participants in the BENEGENE-2 study were screened with a validated assay designed to identify individuals who test negative for neutralizing antibodies to the gene therapy vector.
The European Marketing Authorization Application was based on the primary analysis of BENEGENE-2, which was conducted when 41 participants had reached 15 months of follow-up, with a subsequent data cut provided during review, which monitored some patients up to four years. Clinical trial participants will be followed for up to a total of 15 years, including six years in the BENEGENE-2 study and up to an additional nine years as part of a separate Phase 3 study (NCT05568719) to learn about the long-term safety and efficacy of DURVEQTIX.
Results show that DURVEQTIX significantly reduced the frequency of bleeding compared with usual care. At the 15-month follow-up period, DURVEQTIX patients had a model-based ABR (total bleeds) of 1.44 compared to 4.50 during the lead-in period (p=0.0084), resulting in a 68% reduction. DURVEQTIX eliminated bleeds in 62.2% of patients.
DURVEQTIX was generally well-tolerated, with a safety profile consistent with Phase 1/2 results. The most common adverse reaction (incidence ≥5%) reported in Phase 3 and 1/2 clinical studies was an increase in liver enzymes (transaminases), which was treated with corticosteroids. No serious adverse events related to treatment or associated with infusion reactions, thrombotic events, or FIX inhibitors were reported.
BEQVEZ (fidanacogene elaparvovec-dzkt) U.S. Important Safety Information
What is BEQVEZ?
BEQVEZ is a one-time gene therapy used for the treatment of adults with moderate to severe hemophilia B who are receiving routine prophylaxis, have a current life-threatening bleed or a history of life-threatening bleeds, or have repeated serious spontaneous bleeds.
Before treatment with BEQVEZ, your healthcare professional will conduct a blood test to check for antibodies to the AAVRh74var virus. The results of this testing will help determine if you may receive BEQVEZ.
Before receiving BEQVEZ, tell your healthcare professional about all your medical conditions, including if you:
- Have kidney or liver problems, including hepatitis
- Have factor IX inhibitors or a history of factor IX inhibitors
- Have an active infection
BEQVEZ may cause serious side effects, including:
Increased Liver Enzymes. Most patients treated with BEQVEZ developed elevated liver enzyme levels and most did not experience any symptoms.
Your healthcare professional will monitor liver enzymes and factor IX activity levels before administration of BEQVEZ and frequently following the administration to detect and identify possible elevations in liver enzymes and to monitor your response to BEQVEZ. Your doctor may prescribe a corticosteroid for the treatment of elevated liver enzymes.
Avoid or limit alcohol consumption during the first year following BEQVEZ infusion, as alcohol may reduce the effect of BEQVEZ and may increase liver enzyme levels.
Infusion reactions, including hypersensitivity and severe allergic reactions (anaphylaxis) may occur. Alert your healthcare professional right away if you get any symptoms of hypersensitivity, which may include but are not limited to low blood pressure, fever, heart palpitation, nausea, vomiting, chills, or headache.
BEQVEZ can insert itself into the DNA of cells in the human body. The effect that insertion may have on those cells is unknown but may contribute to a theoretical risk of cancer. There have been no reported cases of cancer caused by treatment with BEQVEZ.
The most common side effect of BEQVEZ is
