Invasive procedures and surgery following etranacogene dezaparvovec gene therapy in people with hemophilia B

J Thromb Haemost. 2025 Jan;23(1):73-84. doi: 10.1016/j.jtha.2024.08.027. Epub 2024 Sep 26.

Abstract

Background: Little information regarding the management of invasive procedures in people with hemophilia B (HB) after undergoing gene therapy is available. Here, we report the management of invasive procedures in people with severe or moderately severe HB who had previously been treated with etranacogene dezaparvovec in the phase 2b and phase 3 Health Outcomes with Padua Gene; Evaluation in Hemophilia B clinical trials (NCT03489291 and NCT03569891).

Objectives: The objective of this study was to describe the use of exogenous FIX, endogenous FIX activity prior to invasive procedures, and peri- and postoperative bleeds in participants who underwent invasive procedures after receiving etranacogene dezaparvovec gene therapy.

Methods: This retrospective analysis included invasive procedures performed within 3 and 2 years following a single infusion of 2 × 1013 gc/kg of etranacogene dezaparvovec in participants in the phase 2b and Health Outcomes with Padua Gene; Evaluation in Hemophilia B trials, respectively. Data for factor (F)IX dosing, duration of postoperative FIX use, FIX activity prior to invasive procedures, and postoperative bleeds were collected and analyzed.

Results: The analysis included 64 procedures in 29 participants: 9 major surgeries, 24 minor surgeries, 11 endoscopies, 3 endoscopies with biopsy/polypectomy, and 17 dental procedures. Uncontaminated endogenous FIX activity corresponded to mild hemophilia or normal levels prior to 98% of all procedures, with a median endogenous FIX activity of 43.8 IU/dL (range, 3.1-113 IU/dL). All major surgeries were managed with exogenous FIX, 67% with ≤4 days of FIX infusion. Most minor surgeries (88%), endoscopies (82%), and dental procedures (94%) were managed with no or a single FIX infusion. Postoperative bleeds occurred after 1 minor surgery and 4 dental procedures. There were no symptomatic thrombotic events or FIX inhibitor developments.

Conclusion: Etranacogene dezaparvovec has the potential to facilitate perioperative management in people with HB by reducing the need for perioperative exogenous FIX and its associated risks.

Keywords: factor IX-Padua; gene therapy; hemophilia B; invasive procedure.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Clinical Trials, Phase III as Topic
  • Dependovirus / genetics
  • Factor IX* / administration & dosage
  • Factor IX* / genetics
  • Genetic Therapy*
  • Genetic Vectors
  • Hemophilia B* / genetics
  • Hemophilia B* / therapy
  • Humans
  • Male
  • Middle Aged
  • Postoperative Hemorrhage* / etiology
  • Postoperative Hemorrhage* / therapy
  • Retrospective Studies
  • Surgical Procedures, Operative / adverse effects
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Factor IX

Associated data

  • ClinicalTrials.gov/NCT03569891
  • ClinicalTrials.gov/NCT03489291