HOPE-B: 5-Year Etranacogene Dezaparvovec Maintains Durable Efficacy and Safety in Hemophilia B, With Steven Pipe, MD

Analysis from the HOPE-B trial shows that a single dose of etranacogene dezaparvovec maintains durable, endogenous factor IX (FIX) Padua expression and produces sustained reductions in bleeding rates among adults with severe or moderately severe hemophilia B, with up to 90% reduction by year 5.1

The data were presented at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition by Steven Pipe, MD, a professor of pediatrics and pathology at the University of Michigan, and provide the longest follow-up data to date from a phase 3 trial of gene therapy in hemophilia B, evaluating long-term durability of FIX expression, efficacy, and safety.1

“For patients who want to be freed from regular regular factor IX infusions, this is really the only therapeutic strategy that can offer that,” Pipe explained in an interview with HCPLive. “A single infusion giving years of stable expression and bleed protection is truly transformative. The earlier patients receive that benefit, the more we can change their long-term joint health trajectory.”1

Etranacogene dezaparvovec (Hemegenix) is an adeno-associated virus vector-based one-time gene therapy. In 2022, the US Food and Drug Administration (FDA) approved etranacogene dezaparvovec as the first gene therapy for adults with hemophilia B who use factor IX prophylaxis therapy and have current or prior life-threatening bleeding or repeated spontaneous bleeding episodes.2,3

“Integrating gene therapy into routine clinical practice requires substantial planning, building infrastructure, training staff, and refining workflows, it’s very different from administering factor replacement,” said Pipe. “But with the right systems in place, we can make the experience manageable for patients by leveraging local labs and minimizing disruptions to their daily lives.”1

These findings were demonstrated by HOPE-B, a phase 3, open-label, single-arm clinical trial where patients received a single intravenous infusion of etranacogene dezaparvovec (2×10¹³ gc/kg) after a ≥6-month lead-in period of standard-of-care FIX prophylaxis to establish baseline bleeding rates. Efficacy endpoints included annualized bleeding rates (ABR), endogenous FIX activity, and exogenous FIX usage. Safety assessments included adverse events, liver function, and long-term risks such as oncogenicity.1

The study population was comprised of adult males with severe or moderately severe hemophilia B (FIX ≤2%) with or without preexisting AAV5 neutralizing antibodies. Of 54 participants treated with etranacogene dezaparvovec, 50 completed 5 years of follow-up.1

Investigators observed a significant reduction in ABR for all bleeds, from 4.16 during the lead-in period to 1.52 during months 7–60 post-gene therapy (rate ratio 0.37; 95% Confidence Interval [CI], 0.18–0.76; P = .0035). Annualized bleed rates at years 1, 2, 3, 4, and 5 were 1.33 (n = 54), 0.91 (n = 54), 0.83 (n = 53), 0.40 (n = 51), and 0.40 (n = 51), respectively. Spontaneous ABR decreased from 1.52 during the lead-in to 0.53 during months 7–60 (P = .0133). Joint ABR decreased from 2.34 to 0.35, and traumatic ABR decreased from 2.01 to 0.34 (P <.0001).1

During years 1-5, mean endogenous FIX activity remained stable at >36%, with similar outcomes in NAb-positive and -negative participants. Exogenous FIX use decreased by 96%, from 257,339 IU/year during the lead-in period to 10,924 IU/year during months 7–60 post-gene therapy (P <.0001). Only 1 participant resumed FIX prophylaxis at 30 months following a decrease in FIX activity to 2-5% and the occurrence of spontaneous bleeding events.1

Over the 5-year follow-up, investigators reported a total of 100 treatment-related adverse events (AE) in 39 participants. Most occurred within the first 4 months post-gene therapy, with only 5 occurring between years 4 and 5. The most frequent AE was alanine aminotransferase elevation (n = 10). According to investigators, only 9 participants received corticosteroids for a mean of 81.4 days (range, 51–130 days). They observed no long-term hepatotoxicity or AAV-related oncogenicity.1

Consenting HOPE-B participants will continue long-term monitoring up to 15 years in the IX-TEND 3003 study.1

Editor’s Note: Pipe reports relevant disclosures with Bayer, BioMarin, Chugai, and others.

References

1. Pipe S, Miesbach W, Recht M, et al. End-of-study analysis of the HOPE-B trial confirms the durable efficacy and safety of etranacogene dezaparvovec hemophilia b gene therapy over 5 years. Abstract presented at the 67th American Society of Hematology Annual Meeting. Orlando, FL. December 6-9, 2025.

2. Heo YA. Etranacogene Dezaparvovec: First Approval. Drugs. Published online February 21, 2023. doi:https://doi.org/10.1007/s40265-023-01845-0

3. Iapoce C. Hemophilia B Gene Therapy Achieves Sustained Benefit Over 4 Years. HCPLive. February 7, 2025. Accessed December 10, 2025. https://www.hcplive.com/view/hemophilia-b-gene-therapy-achieves-sustained-benefit-over-4-years