TOPLINE: 

A single infusion of etranacogene dezaparvovec gene therapy reduced annualized bleeding rates by 63% and maintained stable factor IX activity levels above 30 IU/dL over 5 years in patients with hemophilia B. The treatment enabled 94% of participants to discontinue regular factor IX prophylaxis, with mean factor IX consumption decreasing by 96%.

METHODOLOGY: 

• Current prophylactic treatment for hemophilia B requires lifelong regular intravenous factor IX infusions, which is burdensome from both patient and economic perspectives. Etranacogene dezaparvovec comprises an adeno-associated virus serotype 5 vector and the highly active Padua factor IX variant, with primary analysis showing reduced annualized bleeding rates and mainly low-grade severity adverse events.
• Researchers conducted an open-label, phase 3 study involving 54 men with hemophilia B who had factor IX activity levels < 2 IU/dL, following a lead-in period of factor IX prophylaxis lasting 26 months.
• Participants received a single intravenous dose of etranacogene dezaparvovec at 2×10¹³ genome copies per kilogram of body weight, with a planned follow-up period of 5 years after gene therapy.
• Analysis included adjusted annualized bleeding rates comparing the post-treatment period (months 7 through 60) with the lead-in period, along with factor IX expression and safety outcomes.
• Prespecified subgroup analyses examined outcomes based on age, baseline neutralizing antibody status, and degree of steatosis, with no exclusion for preexisting adeno-associated virus serotype 5 neutralizing antibodies.

TAKEAWAY: 

• Mean factor IX activity level remained stable at 36.1 ± 15.7 IU/dL at year 5, with 80% of participants maintaining levels ≥ 12 IU/dL.
• Adjusted annualized bleeding rates decreased from 4.16 during lead-in to 1.52 during months 7-60, representing a 63% reduction (95% CI, 24-82), with similar reductions in spontaneous (65%), joint (85%), and traumatic (78%) bleeding events.
• Among 52 participants who had a response to treatment, 51 (98%) maintained durable protection from bleeding during months 7-60 after gene therapy.
• Mean annualized consumption of exogenous factor IX decreased by 96%, from 257,339 IU per year during lead-in to 10,924 IU per year during months 7-60 after gene therapy (mean difference, -246,415 IU per year; 95% CI, -287,975 to -204,856).

IN PRACTICE:

“Sustained endogenous factor IX expression and low annualized bleeding rates over a 5-year period were observed after an infusion of etranacogene dezaparvovec,” wrote the authors of the study.

SOURCE:

The study was led by Steven W. Pipe, MD, University of Michigan in Ann Arbor. It was published online on December 7, 2025, in The New England Journal of Medicine.

LIMITATIONS: 

According to the authors, unpredictability of response and interindividual variability of factor IX activity levels remain important considerations when assessing the clinical usefulness for individual patients. The researchers note that longer follow-up will be important to ensure any rare safety signals are captured. 

DISCLOSURES:

This study was supported by uniQure and CSL Behring. Medical writers funded by CSL Behring assisted in manuscript preparation. The data were collected and analyzed by CSL Behring.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.