13 Years of Relief: Success of Gene Therapy for Severe Haemophilia B
- FHS Communications
Imagine a single cut or bruise being a serious risk to your life.
This is the reality for people with severe haemophilia B, caused by a missing protein called factor IX. For years, their lives have revolved around regular injections of this protein to prevent bleeding, a routine that can be painful, costly, and exhausting. Researchers are evaluating the long-term effects of a promising new treatment, a liver-targeted gene therapy using an adeno-associated virus (AAV) vector, to assess its efficacy and safety over 13 years.
Study overview
The idea was to deliver a healthy copy of the factor IX gene, which is associated with severe haemophilia, into the liver using a harmless virus, to prompt the body into producing its own clotting protein. One treatment could, in theory, replace years of injections. The results of the study, Sustained Clinical Benefit of AAV Gene Therapy in Severe Haemophilia B, published in the New England Journal of Medicine, were remarkable. The ten male patients (aged 11–13 years) who received this therapy showed stable levels of factor IX for up to 13 years. They reported far fewer bleeding episodes than before the AVV treatment, meaning they could go about their daily lives with less worry and disruption.
Ten years post-infusion, active transgene expression was observed in hepatocytes, with no evidence of fibrosis or dysplasia. Fifteen vector-related events also occurred, mostly due to transient elevations in liver enzymes.
For people living with haemophilia B, this therapy offers hope for a life with fewer treatments and risks, as high-titer anti-AAV8 antibodies persisted for over ten years.
“This 13-year follow-up study of AAV-mediated gene therapy (scAAV2/8-LP1-hFIXco) in severe haemophilia B demonstrated durable efficacy, a stable factor IX activity, a nearly 10-fold reduction in annual bleeding episodes, and a >12-fold decrease in factor IX concentrate use,” says Professor Johnny Mahlangu, Wits contributing researcher and the Head of Molecular Medicine and Haematology
He says the long-term safety outcomes were reassuring, with no inhibitor formation, thrombosis, chronic liver injury, or vector-related malignancy. “Collectively, these findings establish AAV gene therapy as a safe, durable, and transformative option for haemophilia B,” he explains, noting that this will reduce disease burden and improve patient outcomes.