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

Article

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.

Reference

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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