Hemophilia B Gene Therapy Shows Promise as Long-Term Treatment

Fidanacogene elaparvovec gene therapy is a safe and effective long-term treatment for patients with hemophilia B, according to follow-up data published in the New England Journal of Medicine by researchers from the Children’s Hospital of Philadelphia (CHOP) and the Royal Prince Alfred Hospital in Sydney, Australia.

The initial 2017 trial led by Lindsey A. George, MD, Director of Clinical In Vivo Gene Therapy and an attending physician in the Division of Hematology at CHOP, included 10 male patients with hemophilia B who had factor IX coagulant activity of 2% or less of the normal value.

All patients received fidanacogene elaparvovec, a hepatotropic adeno-associated viral (AAV) vector consisting of a bioengineered capsid, liver-specific promoter, and factor IX–R338L (FIX Padua), at a dose level of 5×10¹¹ vector genomes (vg) per kilogram (kg) of body weight. The follow-up ranged from 28 to 78 weeks.

There were no serious adverse events (AEs) during or after vector infusion. All patients had sustained vector-derived factor IX coagulant activity, and the mean annualized bleeding rate reduced from 11.1 events per year before vector administration to 0.4 events per year after administration.

In the long-term 2025 follow-up study led by John E.J. Rasko, MBBS, BSc, Head of the Department of Cell and Molecular Therapies at the Royal Prince Alfred Hospital, 15 patients received fidanacogene elaparvovec at the same dose level of 5×10¹¹ vg per kg of body weight. The endpoints were safety (AEs and changes in laboratory measures) and efficacy (annualized bleeding rate and factor IX activity). The follow-up ranged from 3 to 6 years.

Of the nine AEs reported in four patients, none were thrombotic or treatment-related. The mean factor IX activity was in the mild hemophilia range, the mean annualized bleeding rate was less than 1, and 10 participants had no treated bleeding episodes. Through liver ultrasounds, steatosis was observed in four patients with weight gain and elevated aminotransferase levels.

“Our findings mark the longest-ever follow-up for patients with hemophilia B who received gene therapy with FIX-Padua,” said Benjamin J. Samelson-Jones, MD, PhD, a lead study author and attending physician in the Division of Hematology at CHOP, said in a press release. “These results offer hope that gene therapy for hemophilia B has the potential to transform the standard of care, offering a future with greater independence and improved quality of life for hemophilia patients.”

This research was funded by Pfizer.

References

Children’s Hospital of Philadelphia. Accessed May 12, 2025. https://www.prnewswire.com/news/children%27s-hospital-of-philadelphia/

George LA, et al. N Engl J Med. 2017;377(23):2215-2227. doi:10.1056/NEJMoa1708538

Rasko JEJ, et al. N Engl J Med. 2025;392(15):1508-1517. doi:10.1056/NEJMoa2307159