Fidanacogene Elaparvovec, an AAV Gene Therapy, Shows Durable Efficacy and Favorable Long-Term Safety for Hemophilia B

June 12, 2025 —New long-term follow-up data on fidanacogene elaparvovec, an investigational adeno-associated virus (AAV) gene therapy for hemophilia B, demonstrate its durable efficacy and a favorable safety profile for up to six years post-administration. The results, published in The New England Journal of Medicine, highlight the therapy’s potential to significantly improve patient outcomes with a low AAV vector dose, potentially mitigating risks associated with higher-dose gene therapies.

The study included 15 adult males with severe or moderately severe hemophilia B who received fidanacogene elaparvovec in a Phase 1/2a trial. Fourteen participants continued into long-term follow-up, with a median observation period of 5.5 years (ranging from 3 to 6 years).

Key Findings from the Study:

• Durable FIX Activity: Mean Factor IX (FIX) activity levels were consistently maintained in the mild hemophilia range (7.4%-44.2%) for up to six years. While a slight decline was observed over time, this was primarily influenced by one participant with alcohol-related liver issues.
• Reduced Bleeding Episodes: The median annualized bleeding rate (ABR) remarkably decreased to 0. A significant majority of participants (67%) experienced no treated bleeding episodes during the long-term follow-up. All reported bleeds occurred when FIX levels were below 25% and were effectively managed with exogenous FIX. No participant resumed prophylactic treatment, and FIX usage remained low. Thirteen surgeries were successfully performed without unexpected bleeding complications.
• Favorable Safety Profile: While most patients (93%) experienced adverse events in the first year after administration, no treatment-related events occurred afterward. Four participants experienced a total of nine serious adverse events after year 1, but none were deemed related to the AAV therapy. Liver surveillance identified steatosis (fatty liver) in four participants, with two cases emerging 3 to 6 years post-treatment, though no liver masses were found. One participant with pre-existing liver disease showed fibrosis progression. Mild, fluctuating increases in liver enzymes were common but remained below critical thresholds. Anti-adeno-associated virus antibodies developed post-treatment and persisted, but no FIX inhibitors were detected. Importantly, no adverse events led to study discontinuation or death, and no thrombotic events were reported.
• Implications of Low Vector Dose: The study authors noted that the observed clinical improvements aligned with those seen in other gene therapy studies that utilized much higher AAV vector doses. This efficacy with a low AAV vector dose has significant implications for reducing potential risks such as dose-dependent random AAV integration, associated genotoxic effects leading to cancer, and the risk of AAV vector being spread through bodily fluids.

Many participants in the study had comorbid conditions, including hepatitis B, hepatitis C, HIV, and joint arthropathy, demonstrating the therapy’s potential in a real-world patient population. These long-term results reinforce fidanacogene elaparvovec’s potential as a transformative, durable treatment option for individuals with hemophilia B.