Research marks one of the longest gene therapy study follow-ups to date
PHILADELPHIA, April 17, 2025 /PRNewswire/ — Researchers at Children’s Hospital of Philadelphia (CHOP) in collaboration with researchers at Royal Prince Alfred Hospital in Sydney, Australia announced the results of the longest follow-up study to date for individuals receiving the gene therapy fidanacogene elaparvovec to treat hemophilia B, a rare, X-linked disorder resulting from a deficiency in coagulation factor IX (FIX) activity. The findings, which support the potential of this gene therapy as a safe and effective long-term solution for hemophilia B, were published today in the New England Journal of Medicine.
Hemophilia B patients have an inherited gene mutation that impairs their ability to produce normal levels of the blood clotting factor IX, resulting in disabling or life-threatening bleeding that can arise spontaneously or be caused by trauma. The current standard of care for hemophilia B is intravenous factor replacement to prevent or manage bleeding episodes, while simultaneously helping to reduce joint damage and other complications caused by frequent bleeding. However, recombinant adeno-associated virus (rAAV) vectors present the opportunity for a one-time disease-altering therapy.
Fidanacogene elaparvovec incorporates a hepatotropic AAV capsid and a high-activity FIX transgene encoding FIX-R338L (also known as FIX-Padua). FIX-Padua, a small natural change in the FIX protein, makes it 8-12 times more effective. Consequently, patients need a much lower dose of the gene therapy to get the right level of FIX activity making this approach a more effective option for treating hemophilia B.
In 2017, Lindsey George, MD, a CHOP hematologist with expertise in gene therapy and Director of Clinical In Vivo Gene Therapy at CHOP, led a team on the first successful hemophilia B Padua trial. Published in the New England Journal of Medicine, the researchers described therapeutic expression of factor IX after gene transfer in 10 participants with hemophilia B with one year of follow up. This new study is a long-term progression of that initial research.
“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 an attending physician in the Division of Hematology at CHOP. “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.”
In the study, Samelson-Jones and his team, along with Professor John Rasko and his team at RPA Hospital, followed 14 male participants, 18 and older, for a period of 3 to 6 years with 8 participants ongoing. Long-term efficacy was achieved at the lowest intravenous dose of rAAV for any indication. Most patients who received the treatment maintained sustained levels of FIX activity and experienced fewer bleeding episodes, reduced join pain and an overall improvement in physical mobility.
Safety data is also encouraging, with no major adverse events linked directly to the therapy. Some patients experienced mild, transient elevations in liver enzyme levels, which were effectively managed with medication. However, post-treatment data suggests that many participants can significantly decrease or even eliminate their reliance on FIX infusions, reducing the burden of treatment and healthcare costs.
This work was supported by Pfizer.
Rasko and Samelson-Jones, et. al. “Fidanacogene Elaparvovec for Hemophilia B: A Multi-Year Follow-Up Study.” NEJM. Online April 17, 2025. DOI: 10.1056/NEJMoa2307159
About Children’s Hospital of Philadelphia:
A non-profit, charitable organization, Children’s Hospital of Philadelphia was founded in 1855 as the nation’s first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, the hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. The institution has a well-established history of providing advanced pediatric care close to home through its CHOP Care Network, which includes more than 50 primary care practices, specialty care and surgical centers, urgent care centers, and community hospital alliances throughout Pennsylvania and New Jersey. CHOP also operates the Middleman Family Pavilion and its dedicated pediatric emergency department in King of Prussia, the Behavioral Health and Crisis Center (including a 24/7 Crisis Response Center) and the Center for Advanced Behavioral Healthcare, a mental health outpatient facility. Its unique family-centered care and public service programs have brought Children’s Hospital of Philadelphia recognition as a leading advocate for children and adolescents. For more information, visit https://www.chop.edu.
Contact: Jennifer Lee
Children’s Hospital of Philadelphia
(267) 426-6084
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