A newly published clinical trial in the New England Journal of Medicine demonstrates the sustained efficacy of Beqvez (fidanacogene elaparvovec) gene therapy as a single-dose treatment for individuals with hemophilia B. The study, a Phase 3 trial, revealed a significant reduction in bleeding episodes among patients following a single infusion of the gene therapy.
Key Findings from the BENEGENE-2 Trial
The BENEGENE-2 trial involved 45 adult males with moderate to severe hemophilia B. The results indicated that a single infusion of Beqvez led to a 71% reduction in the overall annual bleeding rate, decreasing from a mean of 4.42 bleeding episodes per year during a six-month lead-in study (NCT03587116) to 1.28 after treatment (month 3 to month 15 post-infusion). Furthermore, the annual rate of treated bleeds also dropped by 78% during the same period.
Notably, more than half of the patients (64%) remained free of bleeds after receiving the gene therapy, compared to 29% during prophylaxis with regular factor IX infusions. Similarly, the percentage of patients free of treated bleeds increased from 36% to 73% after the gene therapy.
Mechanism of Action
Hemophilia B is characterized by a deficiency in clotting factor IX, leading to impaired blood clotting and an increased risk of bleeding. Beqvez utilizes an adeno-associated virus (AAV) vector to deliver a functional copy of the factor IX gene to liver cells. Once inside the liver cells, the gene instructs the cells to produce factor IX, thereby restoring the body's ability to form blood clots.
Dr. Adam Cuker, clinical director of the Penn Blood Disorders Center and lead researcher, noted that the gene therapy took root within days of infusion, enabling patients' bodies to produce factor IX for the first time. He cautioned against using the word "cure" prematurely but acknowledged the life-changing impact for many patients.
Clinical Significance and Regulatory Approval
Traditional treatment for hemophilia B involves regular infusions of factor IX, which can be burdensome and costly, requiring infusions as frequently as several times a week. Beqvez offers a significant advantage by requiring only a single infusion, potentially freeing patients from the need for frequent treatments.
The U.S. Food and Drug Administration (FDA) approved Beqvez in April 2024 based on the data from this clinical trial. The development of Beqvez was funded by Pfizer.
Safety and Tolerability
While Beqvez was generally well-tolerated, some patients (62%) required glucocorticoids to manage elevated liver enzymes, indicative of liver damage. However, there were no severe reactions related to the gene therapy, such as serious allergic reactions or clotting problems, and none of the patients developed inhibitors against factor IX.
Impact on Patients' Lives
Dr. Cuker emphasized the significant burden that hemophilia places on patients, even when the disease is well-managed. The frequent infusions, treatment costs, and the need to plan around infusions can be a constant source of stress. He highlighted that patients treated with Beqvez have reported a newfound "hemophilia-free state of mind," underscoring the transformative potential of this gene therapy.
