Pfizer recently announced positive top-line results from the phase 3 BENEGENE-2 clinical study, which is currently evaluating the investigational gene therapy fidanacogene elaparvovec for the treatment of adult males with moderately severe to severe hemophilia B. The therapy is designed with bioengineered adeno-associated virus (AAVs) vectors that deliver the genetic codes to stimulate production of the factor IX (FIX) coagulation protein.

A primary endpoint of the study, and key measure of the therapy’s efficacy, is annualized bleeding rate (ABR). Investigators compared (ABR) of participants post-fidanacogene elaparvovec infusion versus a standard prophylaxis regimen with a factor IX (FIX) replacement therapy, which was administered as part routine care during the so-called “lead-in” period lasting for at least six months.

According to a new Pfizer release, The results demonstrated superiority with a mean ABR for all bleeds of 1.3 for the 12 months from week 12 to month 15 compared to an ABR of 4.43 during the lead-in pre-treatment period, resulting in a 71% reduction in ABR after a single dose of fidanacogene elaparvovec. Further secondary endpoints demonstrated a 78% reduction in treated ABR and a 92% reduction in annualized infusion rate.

The company also reported that fidanacogene elaparvovec was “generally well-tolerated,” with a safety profile consistent with phase 1/2 results. In all, 14 serious adverse events (SAEs) were reported in seven (16%) patients, with two assessed as related to treatment, a duodenal ulcer hemorrhage occurring in the setting of corticosteroid use, and an immune-mediated elevation of liver aminotransferase levels. No deaths, SAEs associated with infusion reactions, thrombotic events, or FIX inhibitors were reported.

“The burden people living with hemophilia B face is significant, with many receiving routine infusions or injections which can interfere with their ability to take part in day-to-day activities that many take for granted,” said Adam Cuker, MD, MS, Director, Penn Comprehensive and Hemophilia Thrombosis Program. “The BENEGENE-2 data demonstrate the promise of this gene therapy candidate as a potential one-time option for people living with hemophilia B as a means of reducing the clinical and treatment burden over the long term.”

Pfizer will announce additional trial data updates in early 2023.

Source: Pfizer press release dated December 29, 2022