N Engl J Med

Gene therapy shows 13-year durability in severe hemophilia B

June 13, 2025

Study details: This long-term follow-up study evaluated ten adult males with severe hemophilia B who received a single IV dose of scAAV2/8-LP1-hFIXco gene therapy between 2010 and 2012. Participants were divided into low-, intermediate-, and high-dose cohorts and followed for a median of 13 years. Outcomes included factor IX activity, bleeding rates, factor IX concentrate use, and safety.

Results: Factor IX levels remained stable across all dose groups, with the high-dose cohort achieving a mean of 4.8 IU/dL. The median annualized bleeding rate dropped from 14.0 to 1.5 episodes—a 9.7-fold reduction. Use of factor IX concentrate decreased by a factor of 12.4. Seven of 10 participants no longer required prophylaxis. No participants developed inhibitors, thrombosis, or chronic liver injury.

Clinical impact: This study provides the longest follow-up to date for gene therapy in hemophilia B, demonstrating durable efficacy and a favorable safety profile. A single infusion may offer a transformative, long-term alternative to lifelong factor IX replacement therapy.

Source:

Reiss UM, et al. (2025, June 12). N Engl J Med. Sustained Clinical Benefit of AAV Gene Therapy in Severe Hemophilia B. https://pubmed.ncbi.nlm.nih.gov/40499172/