Fidanacogene Elaparvovec Outperforms Prophylaxis for Hemophilia B

For patients with hemophilia B, a promising new treatment called fidanacogene elaparvovec has shown to be more effective than traditional prophylactic methods. This development was highlighted in a study published on September 26, 2024, in the New England Journal of Medicine. The research was spearheaded by Adam Cuker, M.D., from the University of Pennsylvania Perelman School of Medicine in Philadelphia, and involved a phase 3 open-label study.

Fidanacogene elaparvovec is an adeno-associated virus (AAV) gene-therapy vector that contains a high-activity human factor IX variant. The study administered a dose of 5×10^11 vector genome copies per kilogram of body weight to male patients aged between 18 to 65 years who had hemophilia B and a factor IX level of 2 percent or less. All participants had also undergone at least six months of therapy with prophylactic factor IX concentrate prior to the study.

The screening process for the lead-in study initially included 316 men, out of which 204 were found to be ineligible. Ultimately, 45 men were selected to receive fidanacogene elaparvovec, and 44 of these participants completed at least 15 months of follow-up. The data revealed a significant 71 percent reduction in the annualized rate of bleeding incidents, dropping from 4.42 events at baseline to 1.28 events post-gene therapy. This outcome not only established the noninferiority but also the superiority of fidanacogene elaparvovec over traditional prophylaxis methods.

The study measured the mean factor IX activity at 15 months using a one-stage SynthASil assay, which stood at 26.9 percent. Additionally, 62 percent of the participants required glucocorticoids due to elevated aminotransferase levels or decreased factor IX levels, with treatment initiation ranging from 11 to 123 days.

The authors of the study pointed out that the phase 3 trials demonstrated a favorable benefit-risk profile for fidanacogene elaparvovec. It proved to be efficacious at one of the lowest doses of AAV-based gene therapy explored for hemophilia B to date. This positive outcome suggests significant potential for improving the quality of life for patients dealing with this chronic condition.

The research was funded by Pfizer, the company responsible for developing fidanacogene elaparvovec.