Pfizer's hemophilia B gene therapy is better than standard of care in phase 3 trial

Pfizer’s gene therapy for severe hemophilia B has not only matched standard of care but beat it in a phase 3 study testing whether the treatment can help patients make the protein responsible for blood clotting on their own.

Fidanacogene elaparvovec, which Pfizer licensed from Spark Therapeutics, was being tested in the late-stage trial with 45 male patients who have moderately severe or severe hemophilia B. The pharma giant is developing the gene therapy as a one-time treatment to help patients develop the Factor IX protein needed to clot blood. The current standard of care for these patients is a recurrent Factor IX regimen to prevent and control bleeding.

In the BENEGENE-2 study, the gene therapy demonstrated noninferiority and superiority in annualized bleeding rate of total bleeds compared to the standard of care, meeting the main goal. Patients entering the trial received routine treatment and monitoring for six months before receiving a single dose of fidanacogene elaparvovec.

Patients receiving the gene therapy had 1.3 bleeds between Week 12 after treatment and Month 15, compared to a bleed rate of 4.43 during the six-month monitoring period prior to receiving the medicine. That means the gene therapy led to a 71% reduction in the annualized bleeding rate after a single dose.

On the secondary endpoints, patients taking fidanacogene elaparvovec also had a 78% reduction in treated annualized bleeding rate and a 92% reduction in annualized infusion rate.

Pfizer said the gene therapy was generally well tolerated; however, there were 14 serious adverse events in seven patients, or 16% of the population. Two of those adverse events, a stomach ulcer bleed and liver enzyme elevations, were considered related to treatment. No deaths or serious adverse events associated with infusion were reported.

The clinical trial participants will continue to be monitored in a long-term trial over 15 years, Pfizer said.

Pfizer plans to discuss the gene therapy with regulators in early 2023 as well as present additional data at a scientific conference in the new year.

The FDA has granted the gene therapy breakthrough, regenerative medicines advance therapy and orphan drug designations, while the European Medicines Agency has tagged the gene therapy with PRIority MEdicines (PRIME) and orphan drug designations.

Fidanacogene elaparvovec was licensed from Spark in December 2014, with the small biotech handling phase 1/2 development before Pfizer took over.

CSL Behring was granted FDA approval for a hemophilia B gene therapy called Hemgenix (etranacogene dezaparvovec) in November. The therapy was developed by uniQure, and CSL bought the rights in 2020. The therapy was previously stalled in 2021 by an FDA clinical hold after a report of liver cancer.

Pfizer has late-stage gene therapies in the works in hemophilia B, hemophilia A and Duchenne muscular dystrophy. The Big Pharma also has an antibody called marstacimab in development for hemophilias A and B.

Editor's note: This story was updated at 12:41 p.m. ET on Dec. 29, 2022, to reflect the ownership of Hemgenix and that the FDA approved the gene therapy in November.