Long-term efficacy of etranacogene dezaparvovec in patients with severe haemophilia B

April 2024 Health Innovation Andrea Enguita
Haemophilia - blood disorder abstract.

Etranacogene dezaparvovec, the first gene therapy approved for haemophilia B, demonstrated superior bleeding protection compared to continuous prophylactic factor IX treatment at the 18-month mark in the HOPE-B trial. This updated analysis reveals sustained disease correction 24 months post-gene therapy, further establishing etranacogene dezaparvovec as a safe and effective treatment option for patients with severe or moderately severe haemophilia B.

Moderate-to-severe haemophilia B necessitates lifelong, continuous coagulation factor IX replacement to prevent bleeding. Since 2011, numerous early-phase trials have explored adeno-associated virus (AAV)-based factor IX gene therapies for haemophilia B, demonstrating elevated factor IX activity, reduced bleeding episodes, and decreased reliance on factor IX replacement. Etranacogene dezaparvovec, an adeno-associated virus 5 (AAV5) vector expressing the Padua factor IX variant, represents the first gene therapy approved for haemophilia B treatment.1 Compared to continuous prophylactic factor IX treatment, etranacogene dezaparvovec demonstrated to be superior in terms of bleeding protection 18 months after gene therapy in the HOPE-B trial.2

This article presents post-hoc 24-month efficacy and safety data from the same trial, providing valuable insights into the longer-term effects of etranacogene dezaparvovec in individuals with haemophilia B.2


The phase 3 HOPE-B trial enrolled male patients aged ≥18 years with inherited haemophilia B, classified as severe (plasma factor IX activity level <1%) or moderately severe (plasma factor IX activity level ≥1% and ≤2%), exhibiting a severe bleeding phenotype, and maintained on stable continuous factor IX prophylaxis. Participants underwent treatment with a single infusion of etranacogene dezaparvovec at a dosage of 2 × 1013 genome copies per kg of body weight. The primary endpoint, previously reported, focused on the non-inferiority of the annualised bleeding rate (ABR) during the 52 weeks following stable factor IX expression (defined as months 7-18 after treatment) compared to a lead-in period of at least six months, during which participants received their standard continuous factor IX prophylaxis. These findings are updated here up to month 24.2

Study findings

In total, 54 patients received a single intravenous infusion of etranacogene dezaparvovec and were followed for a median of 26.51 months, after a lead-in period of 7.13 months. In the updated analysis comparing months 7-24 after gene therapy to the lead-in period, the mean adjusted ABR significantly reduced from 4.18 to 1.51 (p=0.0002) for all bleeds and from 3.65 to 0.99 (p=0.0001) for factor IX-treated bleeds. During each 6-month period after gene therapy, at least 67% of participants experienced no bleeding, compared with 26% during the lead-in period. At 24 months after gene therapy, only one (2%) participant had one-stage factor IX activity less than 5%, while 18 (33%) had factor IX activity exceeding 40% (non-haemophilia range), with mean factor IX activity remaining stable and sustained at 36.7% (SD 19.0%). Additionally, 96% of patients expressed endogenous factor IX, remaining free of factor IX prophylaxis at month 24. No new safety concerns were identified, and no serious adverse events or treatment-related deaths occurred. The most common treatment-related adverse events were alanine aminotransferase increase (17%), headache (15%), influenza-like illness (13%), and aspartate aminotransferase increase (9%).2

In conclusion, etranacogene dezaparvovec demonstrates sustained disease correction over 24 months post-gene therapy, offering a safe and effective treatment option for patients with severe or moderately severe haemophilia B.2


  1. Pipe SW, Leebeek F, Recht M, et al. Gene Therapy with Etranacogene Dezaparvovec for Hemophilia B. N Eng J Med. 2023;388:706-18.
  2. Coppens M, Pipe SW, Miesbach W, et al. Etranacogene dezaparvovec gene therapy for haemophilia B (HOPE-B): 24-month post-hoc efficacy and safety data from a single-arm, multicentre, phase 3 trial. Lancet Hematol. 2024;11(4):E265-75.