Beqvez Approved as One-Time Gene Therapy for Hemophilia B

The Food and Drug Administration (FDA) has approved Beqvez^™ (fidanacogene elaparvovec-dzkt) for the treatment of adults with moderate to severe hemophilia B 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.

Beqvez is a one-time AAV-based gene therapy designed to introduce in the transduced cells a functional copy of the factor IX gene encoding a high-activity factor IX variant. The AAVRh74var capsid is able to transduce hepatocytes, the natural site of factor IX synthesis. A single intravenous (IV) infusion of Beqvez results in cell transduction and increase in circulating factor IX activity in patients with hemophilia B.

The approval was based on data from the ongoing, open-label, single-arm phase 3 BENEGENE-2 study (ClinicalTrials.gov Identifier: NCT03861273), which evaluated the efficacy and safety of fidanacogene elaparvovec in 45 adult males with moderately severe to severe hemophilia B (defined as factor IX circulating activity of ≤2 IU/dL). 

Eligible patients were required to have completed 6 months of routine factor IX prophylaxis therapy during the lead-in period (ClinicalTrials.gov Identifier: NCT03587116) after which they received a single IV infusion of fidanacogene elaparvovec. Median follow-up was 2 years (range, 0.4-3.2) from the time of infusion.

The primary endpoint was noninferiority in the annualized bleeding rate (ABR) of total bleeds after fidanacogene elaparvovec infusion compared with baseline ABR during the lead-in period.

Results showed a mean ABR of 4.5 bleeds/year (95% CI, 1.9-7.2) during the baseline period and 2.5 bleeds/year (95% CI, 1.0-3.9) after fidanacogene elaparvovec (treatment difference of -2.1 bleeds/year [95% CI, -4.8, 0.7]), meeting the noninferiority success criterion (upper bound of the 95% CI in the difference was less than 3.0 bleeds/year).

Sixty percent of patients had no bleeds during the post-infusion efficacy evaluation period compared with 29% of those in the prophylaxis arm. A median ABR of zero (range, 0-19) was observed during the efficacy evaluation period vs 1.3 (range, 0-53.9) during the lead-in period.

Six patients (13%) resumed routine factor IX prophylaxis after fidanacogene elaparvovec infusion, starting from 0.4 years to 1.7 years after the gene therapy treatment. One patient had intermittent exogenous factor IX use and a higher ABR after fidanacogene elaparvovec infusion (5.0 bleeds/year) compared with baseline (1.2 bleeds/year) with factor IX activity <5% starting at 0.4 years.

The most common adverse reaction reported was an increase in transaminases. The prescribing information for Beqvez includes risks associated with hepatotoxicity, infusion reactions, and malignancy (eg, hepatocellular carcinoma).

Beqvez is supplied as a vial containing a preservative-free suspension for IV infusion. Treatment is provided as a customized kit containing the number of vials required to meet dosing requirements for each patient based on their weight.