EU Approves Pfizer’s DURVEQTIX® Gene Therapy for Hemophilia B Adults

Pfizer Inc. has received conditional marketing authorization from the European Commission (EC) for DURVEQTIX® (fidanacogene elaparvovec), a gene therapy designed to treat severe and moderately severe hemophilia B in adults without a history of factor IX inhibitors and without detectable antibodies to AAV serotype Rh74. This new therapy enables patients to produce factor IX (FIX) themselves through a one-time dose, as opposed to the current standard which necessitates frequent intravenous FIX infusions.

Alexandre de Germay, Pfizer’s Chief International Commercial Officer, highlighted the substantial medical and treatment challenges faced by hemophilia B patients under the current standard of care. He noted that DURVEQTIX has demonstrated potential to provide long-term protection from bleeds with just a single dose, which could significantly transform hemophilia B care in the European Union.

Hemophilia B is a rare genetic disorder that hampers normal blood clotting due to a deficiency in FIX, resulting in frequent and prolonged bleeding. The common treatment involves regular prophylactic infusions of FIX replacement therapy. Despite these measures, many patients still face the risk of spontaneous bleeding episodes, placing a significant burden on both the individuals and healthcare systems.

Globally, over 42,000 people suffer from hemophilia B, according to the World Federation of Hemophilia. The EC’s conditional marketing authorization for DURVEQTIX is based on the results from the Phase 3 BENEGENE-2 study, which evaluated its efficacy and safety in male patients aged between 18 and 62 with moderately severe to severe hemophilia B. The study demonstrated a statistically significant reduction in the annualized bleeding rate (ABR) for patients receiving DURVEQTIX compared to those on a prophylactic FIX regimen, with efficacy remaining stable from the second to the fourth year post-treatment. The therapy was generally well-tolerated.

The conditional authorization is effective across all 27 EU member states, as well as Iceland, Liechtenstein, and Norway. This follows approvals by the U.S. FDA and Health Canada, where the therapy is marketed as BEQVEZ™. This achievement is part of Pfizer’s longstanding commitment to innovating treatments for hemophilia, a commitment that spans over four decades. Beyond DURVEQTIX, Pfizer has ongoing Phase 3 trials investigating a gene therapy for hemophilia A and another novel therapy, marstacimab, intended for hemophilia A and B patients with and without inhibitors.

DURVEQTIX contains a bio-engineered adeno-associated virus (AAV) capsid and a high-activity variant of the human coagulation FIX gene. The therapy aims to eliminate the need for regular intravenous FIX infusions by allowing patients to produce FIX endogenously after a single treatment.

The BENEGENE-2 study was an open-label, single-arm study involving 45 male participants who had undergone at least six months of routine FIX prophylaxis prior to receiving DURVEQTIX. The study's primary aim was to compare the ABR between gene therapy and FIX prophylaxis. Results from the study indicated that DURVEQTIX significantly reduced bleeding compared to the lead-in period. At 15 months, the model-based total ABR for DURVEQTIX was 1.44, compared to 4.50 during the lead-in, marking a 68% reduction. Additionally, 62.2% of patients experienced no bleeds.

DURVEQTIX was well-tolerated with the most common adverse reaction being an increase in liver enzymes, which was managed with corticosteroids. No serious adverse events related to treatment were reported.

Looking forward, Pfizer continues to monitor the long-term safety and efficacy of DURVEQTIX, following participants for up to 15 years in total, including an additional nine years in a separate Phase 3 study to gather extensive long-term data.

This milestone in the approval of DURVEQTIX represents a significant advancement in the treatment landscape for hemophilia B, holding the promise of improved quality of life for patients and reduced healthcare burdens.