Gene Therapy Breakthrough: 13-Year Study Shows Long-Term Benefits for Hemophilia B Patients

Boston, Ma – A ground-breaking study published in The New England Journal of Medicine reveals that adeno-associated virus (AAV) gene therapy provides sustained production of factor IX, the essential clotting protein missing in individuals with Hemophilia B.

This innovative treatment considerably reduces bleeding episodes and lessens the reliance on regular infusions, offering a new horizon of hope for those affected by this rare genetic disorder.

Long-Term Study Confirms AAV Gene Therapy Efficacy

The extensive 13-year study provides compelling evidence of the lasting impact of AAV gene therapy.

Hemophilia B,resulting from a mutation in the F9 gene,impairs the body’s ability to produce factor IX,leading to potentially life-threatening bleeding.

In the United States, approximately 7,000 people are affected by Hemophilia B, according to data adjusted from Hemophilia Treatment Center (HTC) patients between 2012 and 2018.

Globally, its estimated that nearly 30,000 to 33,000 males have hemophilia, with about 23.5% having hemophilia B. Racial and ethnic groups are affected by this percentage.

The study underscores the underrepresentation of women in hemophilia research, creating a challenge in precisely determining the prevalence among females accurately.

Individuals grappling with severe Hemophilia B often have less than 1% of normal factor IX activity, leading to spontaneous bleeding that can severely damage joints or cause life-threatening complications.

While lifelong infusions of factor IX concentrate remain a common treatment, they are often costly, invasive, and time-consuming.

The AAV Gene Therapy Approach

Researchers began exploring AAV gene therapy back in 2014 as a method to deliver a functional copy of the F9 gene directly into the liver. The body can then, theoretically, produce its own factor IX.

Upon receiving a single intravenous dose, a notable number of patients were able to discontinue regular infusions and experienced a notable reduction in bleeding incidents.

Ten men with severe Hemophilia B were monitored over 13 years after receiving a single dose of scAAV2/8-LP1-hFIXco. This vector delivered the factor IX gene using a harmless virus.

The participants were stratified into low, intermediate, and high-dose groups based on the viral particle count per kilogram of body weight, with the therapy administered intravenously.

Key Findings: Safety and Effectiveness

The research project, managed by teams at St. Jude Children’s Research Hospital and University College London, rigorously evaluated both safety and effectiveness via lab tests, monitoring bleeding frequency, factor IX activity, and factor IX concentrate usage post-treatment.

The data showed a robust safety profile throughout the 13-year observation period.

No participants developed any antibodies against the therapy or reported severe liver complications.

Two participants were diagnosed with cancer, but experts concluded that the occurrences were likely unrelated to the gene-therapy.

In the high-dose group, factor IX levels remained consistently around 4.8 international units per deciliter (IU/dL), markedly reducing bleeding events.

Before the treatment,the median bleeding rate averaged 14 episodes per year; post-treatment,it plummeted to approximately 1.5,reflecting a 9.7-fold decrease. The high-dose group saw an even more substantial reduction, with bleeding decreasing 16.4-fold.

Furthermore,seven out of the ten participants no longer required regular preventative treatment.

Factor IX concentrate use also witnessed a significant decline-from a median of 2,613 international units per kilogram per year (IU/kg/year) before treatment to just 367 after, a 12.4-fold reduction.

The high-dose group saw even more dramatic results, with usage dropping to 171 IU/kg/year, marking a 14.7-fold reduction.

One participant underwent a liver biopsy 10 years post-treatment. The liver was healthy, with continuous gene activity in certain cells.

The study also revealed persistent, elevated levels of antibodies to the AAV virus. This could limit the potential for repeated treatments later in life.

Implications and Future Research

These results confirm that AAV gene therapy is both safe and effective in decreasing bleeding and lowering the need for medication in patients with Hemophilia B over extended periods.

The researchers highlight the necessity for ongoing monitoring aimed at identifying and evaluating any rare risks. Further investigations are needed to fully understand gene expression durability and strategies to overcome immune system challenges, as AAV gene therapy might remain a one-time treatment option for the majority of patients.

Do you have any personal experiences with Hemophilia B treatments, or thoughts on the potential of gene therapy? Share your comments below!