Hemophilia B Gene Therapy Achieves Sustained Benefit Over 4 Years

Steven Pipe, MD

Credit: University of Michigan

A one-time infusion of etranacogene dezaparvovec-drlb (HEMGENIX) gene therapy continued to demonstrate long-term sustained efficacy and safety in adults with hemophilia B over 4 years in the pivotal Phase 3 HOPE-B study.¹

Announced by CSL on February 7, 2025, these data, presented at the 18th Annual Congress of the European Association for Hemophilia and Allied Disorders (EAHAD), showed the gene therapy delivered sustained factor IX activity levels, offered greater bleed protection than prophylactic treatment, and maintained favorable safety over time.

“Hemophilia B can cause spontaneous bleeds into the joints, resulting in extreme pain and progressive, arthritis-like damage, which can lead to permanent physical debility,” said Steven Pipe, MD, the Laurence A. Boxer Research Professor of Pediatrics and Communicable Diseases and the Hemophilia and Coagulation Disorders Program Director at the University of Michigan. “These results underscore the ability of HEMGENIX to offer long-term bleed protection with a one-time treatment, resulting in dramatic decreases in all annual bleed rates, including joint bleeds, and sustained independence from regular prophylactic infusions.”

A rare disease caused by mutations in the F9 gene leading to low functional clotting factor IX levels, hemophilia B leaves patients vulnerable to bleeding in the joints, muscles, and internal organs. Typical treatments require a long-term prophylactic infusion of factor IX to supplement low functional clotting factor levels.²

In 2022, the US Food and Drug Administration (FDA) approved etranacogene dezaparvovec as the first gene therapy for adults with hemophilia B using factor IX prophylaxis therapy, who have current or previous life-threatening bleeding, or who experience repeated spontaneous bleeding episodes. It marked the only approved gene therapy for adults with hemophilia B with and without AAV5-neutralizing antibodies, expanding the number of eligible patients.³

The open-label, single-dose, single-arm pivotal HOPE-B trial enrolled 54 adult males with severe or moderately severe hemophilia B, with or without pre-existing AAV5 neutralizing antibodies, and infused a single dose of the gene therapy. Among those who received the gene therapy, 51 participants completed 4 years of follow-up.¹

Upon analysis, etranacogene dezaparvovec achieved mean factor IX levels of 41.5 IU/dL (n = 50) at Year 1, 36.7 IU/dL (n = 50) at Year 2, 38.6 IU/dL (n = 48) at Year 3, and 37.4 IU/dLL (n = 47) at Year 4 post-infusion. The mean adjusted annualized bleeding rate (ABR) for all bleeds was reduced by approximately 90% from lead-in (ABR, 4.16; n = 54) to Year 4 (ABR, 0.40; n = 51).

Further analysis showed a reduction in joint bleeds from lead-in (ABR, 2.34) to Year 4 (ABR, 0.09) after the gene therapy. Notably, at Year 4, CSL reported 94% of patients were free of continuous prophylaxis, with no patients returning to continuous prophylaxis between Years 3 and 4 post-treatment.

The safety profile of etranacogene dezaparvovec was well-tolerated, with no serious adverse events related to the gene therapy. A total of 96 treatment-related AEs were identified, with most (96%) occurring in the first 6 months post-infusion. The most common adverse event was an increase in alanine transaminase (ALT), for which 9 patients received reactive corticosteroids over a mean of 81 days.

“These data continue to instill confidence in the clinical benefits of HEMGENIX, highlighting the remarkable impact of this one-time treatment to reduce the frequency of bleeds in people with hemophilia B and improve quality of life by alleviating the burden of ongoing factor IX prophylactic treatment,” said Andres Brainsky, vice president of research and development in hematology at CSL.¹ “CSL is committed to continuing to provide ongoing data analyses of HEMGENIX, ensuring that healthcare providers and patients have the necessary information to make informed decisions about treatment options.”

References

1. _{CSL Behring’s gene therapy HEMGENIX® (etranacogene dezaparvovec-drlb) four years post-infusion data continue to show sustained efficacy and safety in adults with hemophilia B. CSL. February 7, 2025. Accessed February 7, 2025. https://newsroom.csl.com/2025-02-07-CSL-Behrings-Gene-Therapy-HEMGENIX-R-etranacogene-dezaparvovec-drlb-Four-Years-Post-Infusion-Data-Continue-to-Show-Sustained-Efficacy-and-Safety-in-Adults-with-Hemophilia-B.}
2. _{Alshaikhli A, Killeen RB, Rokkam VR. Hemophilia B. [Updated 2023 Oct 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560792/}
3. _{Johnson V. FDA approves first gene therapy for hemophilia B. HCP Live. November 23, 2022. Accessed February 7, 2025. https://www.hcplive.com/view/fda-approves-first-gene-therapy-hemophilia-b.}