Revolutionary Single-Dose Gene Therapy Offers New Hope for Adults with Hemophilia B

A groundbreaking gene therapy for hemophilia B has shown remarkable success in reducing bleeding episodes and improving the quality of life for adult patients, according to a recent international phase III clinical trial published in the New England Journal of Medicine.

The study revealed that adults with hemophilia B experienced a 71% average reduction in bleeding episodes after receiving a single infusion of the gene therapy. This significant improvement led to the FDA's approval of the therapy, known as fidanacogene elaparvovec, in April 2024.

Hemophilia B is a genetic disorder affecting blood clotting, primarily in men, caused by a deficiency in clotting factor IX, which can lead to spontaneous bleeding and joint damage if untreated. The new gene therapy works by enabling the liver to produce factor IX, effectively allowing patients' blood to clot normally.

Dr Adam Cuker, lead author of the study and clinical director of the Penn Blood Disorders Center, said, “What we saw from patients in this study was that within a few days of receiving the gene therapy infusion, it took root, and their bodies started making factor IX for the first time in their lives.” More than half of the 45 participants in the study experienced no bleeding episodes after the gene therapy.

The therapy represents a significant advancement over the current standard of care, which involves regular prophylactic infusions of factor IX. These infusions can be burdensome for patients, requiring frequent treatments and careful planning. In contrast, the new gene therapy requires only a single dose, potentially freeing patients from the need for ongoing factor IX treatments.

While the researchers are cautious about using the term "cure," many patients have reported a transformative impact on their lives. Dr Cuker described patients experiencing a new "hemophilia-free state of mind," free from the constant worry about bleeds, treatments, and associated costs.

The FDA's approval of fidanacogene elaparvovec marks the second gene therapy approved for hemophilia B treatment. The first, etranacogene dezaparvovec-drlb, was approved in November 2022. Penn Medicine, which was a top-enrolling site for the clinical trial, is now one of several medical centers in the US offering these innovative treatments.

As with any new therapy, there are potential side effects to consider. The most common adverse effect observed was an immune system reaction targeting liver cells, which could potentially render the therapy ineffective if not promptly treated. In the study, affected patients were successfully treated with steroids to mitigate this reaction.

The long-term effects of the therapy will continue to be monitored, with patients in the study being followed for at least 5 years. However, the initial results suggest that this single-dose gene therapy could be a game-changer for adults living with hemophilia B, offering the potential for a life free from the burden of constant treatment and the fear of spontaneous bleeding.

References

Penn Medicine News. Single-Dose Gene Therapy is Potentially Life-Changing for Adults with Hemophilia B. Published September 25, 2024. Accessed November 6, 2024. https://www.pennmedicine.org/news/news-releases/2024/september/gene-therapy-is-potentially-life-changing-for-hemophilia-b

Cuker A, Kavakli K, Frenzel L, et al. Gene therapy with fidanacogene elaparvovec in adults with hemophilia B. N Engl J Med. 2024;391(12):1108-1118. doi:10.1056/NEJMoa2302982