Gene Therapy Superior to Factor IX Prophylaxis in Hemophilia B

A single infusion of fidanacogene elaparvovec — an FDA-approved gene therapy for hemophilia B — resulted in a 71% reduction in bleeding episodes compared to factor IX (FIX) prophylaxis, according to findings from a Phase III clinical trial published Wednesday in the New England Journal of Medicine.

Fidanacogene elaparvovec (marketed as Beqvez by Pfizer) is an adeno-associated virus (AAV)-based gene therapy designed to introduce a functional copy of the FIX gene, enabling the production of a high-activity FIX variant.

The trial included 45 patients, each receiving 5×10¹¹ vector genome copies per kilogram. Of the 44 patients who completed at least 15 months of follow-up, researchers observed a decrease in the annualized treated bleeding rate from 3.34 to 0.73 episodes — a 78% reduction. The therapy also led to a 92.3% decrease in annualized infusion rates and a 92.4% reduction in FIX consumption.

Of the 316 participants who underwent screening for the lead-in study, 204 (64.6%) were not eligible, with 188 (59.5%) excluded due to the presence of anti-AAV neutralizing antibodies. Despite this limitation, the gene therapy demonstrated long-lasting efficacy in nearly 90% of participants who completed the trial.

According to the study authors, fidanacogene elaparvovec offers a sustained increase in FIX levels. While some patients required glucocorticoid therapy due to increased aminotransferase levels, the treatment was generally well-tolerated, with no major safety concerns reported.

Further studies are necessary to explore the long-term effects of the therapy, including liver health and predictors of treatment response. However, the findings suggest that fidanacogene elaparvovec is a promising alternative to FIX prophylaxis, with the potential to reduce patients’ dependence on regular factor replacement therapies.

“We hear from people born with hemophilia that—even if their disease is well-managed—there’s this burden that’s always in the back of their mind,” lead author Adam Cuker, MD, MS, said in a news release. “The frequent infusions, the cost of treatment, the need to plan for infusions when traveling, what happens if they do experience a bleed, and so on, is always there.

“Now that we have patients who were treated on this study and are essentially cured of their hemophilia, they’re telling us about realizing a new, ‘hemophilia-free state of mind.’ As a physician, it’s amazing to see my patients so happy with their new reality.”