Gene Therapy Reduces Bleeding in Men With Hemophilia B

Fidanacogene elaparvovec is designed to deliver healthy genes to liver cells

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Treatment with the experimental gene therapy fidanacogene elaparvovec led to significant reductions in bleeding rates for men with moderately severe to severe hemophilia B who participated in a Phase 3 clinical trial.

That’s according to top-line data from the study BENEGENE-2 (NCT03861273), recently announced by the therapy’s developer, Pfizer.

“We are proud to advance the latest innovation for people living with hemophilia B and are encouraged by the potential of this investigational gene therapy,” said Chris Boshoff, MD, PhD, chief development officer for oncology and rare disease product development, in a press release.

Hemophilia B is caused by gene mutations that impair the function of clotting protein factor IX (FIX). Fidanacogene elaparvovec, or SPK-9001, is designed to deliver a healthy version of this gene to cells in the liver — the main producers of clotting factors in the body — to restore functional FIX production. The therapy delivers its genetic cargo using an engineered viral vector.

Data from an earlier Phase 1/2 study (NCT02484092), which tested fidanacogene elaparvovec in 15 men with hemophilia B, suggested it was well tolerated and able to lower bleeding rates.

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Gene therapy’s effect on hemophilia B

Pfizer sponsored BENEGENE-2 to further explore the therapy’s safety and effectiveness. The study included 45 men with moderately severe to severe hemophilia B, defined as those in whom FIX activity levels are at 2% or lower than normal. All tested negative for antibodies against the therapy’s viral vector.

After a lead-in study (NCT03587116) wherein participants were treated with standard preventive FIX replacement therapy (prophylaxis) for a minimum of six months, all received a single fidanacogene elaparvovec infusion. The study’s main goal was to assess the effect of treatment on bleeding rates, comparing the six months before therapy with months 3 to 15 after treatment, effectively allowing three months for it to start being effective.

Results showed the mean annual bleeding rate was 71% lower after gene therapy compared with the six-month lead-in period (1.3 vs. 4.43 bleeds per year). The rate of bleeds requiring treatment was similarly decreased, by 78%, while the annual rate of replacement therapy infusions decreased by 92%.

At month 15, mean FIX activity was at 27% of normal and by month 24 it was at 25%. FIX activity higher than 5% is considered clinically meaningful for this population.

“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,” said Adam Cuker, MD, director of the Comprehensive and Hemophilia Thrombosis Program at the University of Pennsylvania.

Fidanacogene elaparvovec was generally well tolerated and its overall safety profile was consistent with earlier studies’ results. Two serious side effects related to treatment were reported: an ulcer with bleeding in the digestive tract in a patient taking corticosteroids and an instance of elevated liver enzyme levels, which is typically associated with liver damage and inflammation. No deaths, blood clotting events, or cases of neutralizing antibodies against FIX were reported.

Participants will continue to be regularly evaluated for up to 15 years to assess long-term safety and efficacy outcomes. Additional findings will be presented at a conference in the coming months, according to Pfizer.

“We are extremely appreciative of those who are participating in the trial and to the investigators contributing to this innovative research as we work to unlock the full potential of gene therapies for people living with hemophilia,” Boshoff said.