Study Shows Long-Term Benefits of Discontinued Hemophilia B Gene Therapy

Rare Daily Staff

A long-term follow-up study of individuals receiving a gene therapy to treat the rare blood disorder hemophilia B that was pulled from the market due to a lack of interest, shows that it is safe and effective.

The results of the study, the longest-term follow-up study of a hemophilia B gene therapy to date, were published today in the New England Journal of Medicine. Researchers at Children’s Hospital of Philadelphia (CHOP) performed the study of the gene therapy fidanacogene elaparvovec in collaboration with researchers at Royal Prince Alfred Hospital in Sydney, Australia.

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, gene therapies represent an opportunity for a one-time disease-altering therapy.

Fidanacogene elaparvovec is 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 the approach a more effective option for treating hemophilia B.

“Our findings mark the longest-ever follow-up for patients with hemophilia B who received gene therapy with FIX-Padua,” said Benjamin Samelson-Jones, 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 John Rasko and his team at RPA Hospital, followed 14 male participants, 18 and older, for a period of three to six years with eight 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.

There were 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 suggest that many participants can significantly decrease or even eliminate their reliance on FIX infusions, reducing the burden of treatment and healthcare costs.

Pfizer funded the study. The company had marketed fidanacogene elaparvovec as Beqvez, but in February discontinued it because of limited interest from patients and physicians. Even though the company won approval for the gene therapy in April 2024, no one was ever treated with the commercial product.

Photo: Benjamin Samelson-Jones, a lead study author and an attending physician in the Division of Hematology at CHOP