General Information

Beqvez (fidanacogene elaparvovec-dzkt) is an adeno-associated virus vector-based gene therapy.

Beqvez is specifically indicated for the treatment of adults with moderate to severe hemophilia B (congenital factor IX deficiency) who:

•  Currently use factor IX 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 (AAVRh74var) capsid as detected by an FDA-approved test

Dosing/Administration

Beqvez is supplied as a one-time single-dose intravenous infusion only.

Perform baseline testing to select patients, including testing for pre-existing antibodies to AAVRh74var, factor IX inhibitor presence, and liver health tests.

The recommended dose of Beqvez is 5 × 1011 vector genomes per kg (vg/kg) of body weight. Dose based on adjusted body weight for those with a BMI >30 kg/m2

Administer Beqvez as an intravenous infusion after dilution in 0.9% sodium chloride with 0.25% human serum albumin (HSA) with a final volume of 200 mL over approximately 60 minutes.

Mechanism of Action

Beqvez is an adeno-associated virus (AAV)-based gene therapy designed to introduce in the transduced cells a functional copy of the FIX gene encoding a high-activity FIX variant. For eligible patients 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 having to receive frequent infusions of FIX, as is the current standard of care.

Beqvez (fidanacogene elaparvovec-dzkt) is designed to introduce in the transduced cells a functional copy of the factor IX gene encoding a high-activity FIX variant (FIX-R338L, hFIX Padua).  The AAVRh74var capsid is able to transduce hepatocytes, the natural site of factor IX synthesis. Single intravenous infusion of Beqvez results in cell transduction and increase in circulating factor IX activity in patients with hemophilia B.

Side Effects

The most common adverse effect associated with the use of Beqvez in clinical trials was an increase in transaminases.

Clinical Trial Results

The FDA approval of Beqvez was based on results from the phase 3, open-label, single-arm BENEGENE-2 trial 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% 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.

The study enrolled 45 participants. Eligible study participants had completed a minimum of six months of routine FIX prophylaxis therapy during the lead-in study and received a single intravenous infusion of Beqvez at a dose of 5 x 1011 vg/kg of body weight. 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% of patients compared to 29% 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.