Gene therapy for hemophilia B has reached a significant milestone: more than a decade after a single treatment, patients continue to experience stable benefits with minimal safety concerns, according to a 13-year follow-up study.
Hemophilia B is a genetic bleeding disorder caused by a deficiency of clotting factor IX, leading to frequent, sometimes life-threatening bleeding episodes. Traditional management requires regular infusions of factor IX concentrate to prevent or control bleeds—a lifelong and burdensome regimen.
In a landmark study led by Amit Nathwani, MBChB, PhD, at University College London and reported by MedPage Today in June 2025, ten men with severe hemophilia B received a single intravenous dose of a gene therapy vector—specifically, a self-complementary adeno-associated virus (AAV) carrying a healthy factor IX gene. The treatment aimed to enable patients’ own cells to produce factor IX, potentially reducing or eliminating the need for ongoing infusions.
The results, now extending to a median of 13 years post-infusion, are remarkable. Across all dose groups, factor IX expression remained stable. Most notably, the median annualized bleeding rate plummeted from 14 episodes per year to just 1.5—a nearly tenfold reduction. The use of factor IX concentrate also dropped by more than twelvefold, dramatically easing the daily burden of disease.
Safety data from the study are also encouraging. No late-onset issues, such as factor IX inhibition, thrombosis, or recurrent liver inflammation, were observed. While two patients developed cancers—lung and prostate—years after gene therapy, expert review found no evidence linking these cases to the treatment itself. The majority of therapy-related adverse events were mild and temporary, such as transient liver enzyme elevations.
Importantly, the study highlighted that gene therapy’s effectiveness can be influenced by individual patient factors. Three participants with advanced joint disease returned to regular factor IX prophylaxis within four years after treatment, as their lower factor IX levels (1–3 IU/dL) were insufficient to prevent joint bleeding. This underscores the impact of underlying joint health and biological variation on outcomes.
The pioneering work by Nathwani’s team paved the way for the FDA approval of modern gene therapy products like etranacogene dezaparvovec (Hemgenix) and fidanacogene elaparvovec (Beqvez). However, questions about how long gene therapy benefits would last remained—until now.
This 13-year follow-up provides robust evidence that a single AAV-mediated gene therapy can offer durable, long-term relief from bleeding for people with severe hemophilia B, with manageable safety risks. While gene therapy is not a perfect solution for every patient—especially those with pre-existing joint damage—it represents a profound shift from chronic management to potentially one-time, lasting intervention.
For the hemophilia community, these results offer renewed hope that gene therapy can bring not just fewer bleeds and less treatment, but a better quality of life for years to come.
