Hemophilia B Gene Therapy Significantly Reduces Annual Bleeds in Phase 3 Trial


The FDA granted fidanacogene elaparvovec breakthrough, regenerative medicines advance therapy, and orphan drug designations.

An infusion of fidanacogene elaparvovec reduced the annualized bleeding rate (ABR) of total bleeds versus a standard exogenous prophylaxis regimen of Factor IX (FIX) for adult males with moderate to severe hemophilia B, according to positive top-line results from phase 3 of the BENEGENE-2 study.

The BENEGENE-2 trial met its primary endpoint of non-inferiority and superiority in the ABR of total bleeds. Key secondary endpoints showed that fidanacogene elaparvovec reduced treated ABR by 78%. There was also a 92% reduction in annualized infusion rate.

“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, in a Pfizer press release.

Hemophilia primarily affects males. It is a rare genetic bleeding disorder that slows or prevents blood from clotting. In 2021, nearly 38,000 people had hemophilia B.

Patients with hemophilia B are deficient of FIX, a specific blood protein that helps the blood to clot. Fidanacogene elaparvovec, a bio-engineered adeno-associated virus (AAV) capsid and coagulantion FIX gene, helps patients to produce FIX on their own. Its aim is to become an effective alternative to exogenous FIX.

In a lead-in study, participants were given 6 months of routine exogeneous FIX prophylaxis therapy. Following this therapy, patients were administered a 5e11 vg/kg intravenous (IV) dose of fidanacogene elaparvovec.

After 15 months, the mean FIX activity was increased 27%, which is significantly higher the pre-specified threshold of 5%. Participants in the BENEGENE-2 study will be followed for 15 years.

Among participants, the mean ABR also decreased to 1.3 in 12 months. The mean ABR with IV fidanacogene elaparvovec was more than 3 times less than mean ABR during lead-in treatment with FIX prophylaxis therapy (4.43).

Overall, this 1-time option can “reduc[e] the clinical and treatment burden over the long term,” Cuker said.

The safety profile of fidanacogene elaparvovec is consistent with results from phases 1 and 2. Some of the more serious adverse events related to treatment were duodenal ulcer hemorrhage and increased levels of immune-mediated liver aminotransferase. However, the treatment was generally well tolerated and there were no thrombotic events or deaths.

Pfizer is studying gene therapy in 3 programs for populations of high unmet need, including hemophilia A and Duchenne muscular dystrophy. They will present current data in early 2023 at a scientific conference.

“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, Oncology and Rare Disease, Pfizer Global Product Development, in a recent press release.


Pfizer. Pfizer Announces Positive Top-Line Results from Phase 3 Study of Hemophilia B Gene Therapy Candidate. News Release. December 29, 2022. Accessed on January 3, 2022. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-announces-positive-top-line-results-phase-3-study

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