- 94% of patients (51 of 54) remained free from the burden of continuous prophylaxis treatment through five years following a single infusion of HEMGENIX®, demonstrating sustained therapeutic benefit
- At year five, mean factor IX activity levels remained strong at 36.1% and HEMGENIX® continued to demonstrate a favourable safety profile, reinforcing its durable efficacy
- More than 75 individuals across eight countries have received HEMGENIX® in real-world settings, reflecting growing global adoption
MARBURG, GERMANY – December 7, 2025 — Global biopharma leader CSL (ASX:CSL) today announced five-year (60-month) results from the pivotal Phase 3 HOPE-B study, confirming the long-term durability and safety of a one-time infusion of HEMGENIX® (etranacogene dezaparvovec) in adults living with moderate to severe haemophilia B. Published in the New England Journal of Medicine (NEJM) and presented simultaneously at the American Society of Hematology (ASH) Annual Meeting, the data reaffirm HEMGENIX®’s consistent performance over time to deliver durable factor IX activity levels, sustained bleed protection compared to prophylaxis treatment, and continued freedom from routine prophylaxis. HEMGENIX® remains the only commercially available gene therapy for adults with haemophilia B and can be used in patients with or without AAV5 neutralising antibodies.
“The five-year HOPE-B results mark a pivotal milestone for gene therapy, providing clear, long-term data of the ability of HEMGENIX® to potentially transform care for adults with haemophilia B,” said Steven Pipe, MD, Professor of Pediatrics and Pathology, Hemophilia and Coagulation Disorders Program and the Special Coagulation Laboratory, University of Michigan. “For those who have relied on frequent prophylactic infusions, achieving lasting bleed control from a single treatment offers the potential for greater day-to-day freedom and a life less burdened by the demands of ongoing therapy.”
In the Phase 3, open-label, single-dose, single-arm HOPE-B trial, 54 adult male participants with severe or moderately severe haemophilia B, with or without preexisting AAV5 neutralising antibodies, were infused with a single dose of HEMGENIX®. Of the 54 participants, 50 completed five years of follow-up. The five-year follow-up analysis demonstrated:
- Durable Factor IX Activity: Mean factor IX activity levels were sustained at greater than 36% during years one through five post-infusion: mean factor IX levels of 41.5 IU/dL (n=50) at year one, 36.7 IU/dL (n=50) at year two, 38.6 IU/dL (n=48) at year three, 37.4 IU/dL (n=47) at year four, and 36.1 IU/DL (n=48) at year five.
- Sustained Bleed Protection: The mean adjusted annualised bleeding rate (ABR) for all bleeds was reduced by approximately 90% from the lead-in (4.16, n=54) compared to year five (0.40, n=51) post-infusion. Additionally, joint bleeds were reduced by 93% from lead-in (mean ABR of 2.34 at lead-in to 0.16 at year five) and spontaneous bleeds were reduced by 94% (mean ABR of 1.52 during lead-in versus 0.09 during year five).
- Freedom from Prophylaxis: 94% of patients remained free of continuous prophylaxis treatment following their one-time gene therapy infusion. This rate has remained consistent over time, with only one participant resuming continuous factor IX prophylaxis at month 30 post-infusion.
- Favourable Safety Profile: No serious adverse events were related to treatment with HEMGENIX®. HEMGENIX® was generally well-tolerated, with a total of 100 treatment-related adverse events (TRAEs), most of which occurred in the first four months post-infusion. Only five TRAEs were reported between years four and five. The most common adverse events were an increase in alanine transaminase (ALT), for which nine (16.7%) participants received supportive care with reactive corticosteroids for a mean duration of 81.4 days (standard deviation: 28.6; range: 51-130 days).
“We are incredibly proud to share the five-year results from the HOPE-B study, which reinforce the lasting impact of HEMGENIX® as a one-time treatment option for adults with haemophilia B,” said Deborah Long, MD, FCCP, Senior Vice President and Head, Medical Affairs, CSL. “These results highlight the meaningful difference HEMGENIX® can make—helping people experience fewer bleeds compared to prophylaxis treatment and freeing them from the burden of regular ongoing treatment. We remain committed to expanding access to this important treatment.”
Although the five-year data mark the final analysis for the HOPE-B study, participants who consent will continue to be monitored in the IX-TEND 222-3003 extended follow-up study (NCT05962398), which will track patients for up to 15 years post-treatment.
The multi-year clinical development of HEMGENIX® was led by uniQure (Nasdaq: QURE) and sponsorship of the clinical trials transitioned to CSL after it licensed global rights to commercialise the treatment. CSL also established a post-marketing registry to generate additional long-term safety, efficacy and durability data.
HEMGENIX® has received regulatory approval in the United States, Canada, the UK, Switzerland, Australia, Saudi Arabia, Taiwan, South Korea, Singapore, and Hong Kong, and conditional marketing authorisation from the European Commission (EC) for the European Union and European Economic Area. To date, more than 75 individuals across eight countries have received HEMGENIX® in real-world settings.
Haemophilia B is a life-threatening rare disease. People with the condition are particularly vulnerable to bleeds in their joints, muscles, and internal organs, leading to pain, swelling, and joint damage.1 The constant worry of a bleed means that their daily activities can be restricted, even for things as simple as going up and down stairs.1-3 Current treatments for moderate to severe haemophilia B include life-long prophylactic infusions of Factor IX to temporarily replace or supplement low levels of the blood-clotting factor.1 Many people with haemophilia find themselves continually confronted with the mental and emotional impact of managing their condition, and rarely have their minds free of haemophilia.2
About HEMGENIX®
HEMGENIX® (etranacogene dezaparvovec) is an in vivo gene therapy that reduces the rate of abnormal bleeding in eligible people with haemophilia B by enabling the body to continuously produce Factor IX, the protein that is deficient in people with the disease.4 It uses a non-infectious viral vector derived from an adeno-associated virus (AAV5).4 The AAV5 vector carries the Padua gene variant of Factor IX to the target cells in the liver, generating Factor IX proteins that are 5–8x more active than normal.5 These genetic instructions remain in the target cells, but generally do not become a part of a person’s own DNA.4 Once delivered, the new genetic instructions allow the cellular machinery to produce stable levels of Factor IX.6
About the Pivotal HOPE-B Trial
The pivotal Phase III HOPE-B trial is an ongoing, multinational, open-label, single-arm study to evaluate the safety and efficacy of etranacogene dezaparvovec.7 A total of 54 adult patients with haemophilia B, classified as having moderately severe to severe haemophilia B and requiring prophylactic Factor IX replacement therapy, were enrolled in a prospective, 6-month or longer observational period. During this period, patients continued to use their current standard of care therapy to establish a baseline annual bleeding rate (ABR).7 After the 6-month lead-in period, patients received a single intravenous administration of etranacogene dezaparvovec at the 2x1013 gc/kg dose. Patients were not excluded from the trial based on pre-existing neutralising antibodies (NAbs) to AAV5.7
The results of the Phase III HOPE-B trial demonstrated the long-lasting efficacy and safety of etranacogene dezaparvovec as well as the ongoing benefit of this treatment for people living with haemophilia B, with long-term bleed protection provided by a one-time infusion.4,8,9
Additional trial data
CSL220 (formerly AMT-060) has a similar structure to etranacogene dezaparvovec, differing only in a single amino acid substitution in the F9 gene.10 In a Phase I/II study, the durability of CSL220 was assessed in two cohorts of adult patients with severe/moderately severe haemophilia B receiving different single-infusion doses.10 Mean Factor IX activity remained stable in both cohorts at 8 years (Cohort 1: n=3, Year 8: 4.9 IU/dL; Cohort 2: n=5, Year 8: 5.6 IU/dL), mean ABR was maintained at Year 8 (Cohort 1: 2.2; Cohort 2: 1.0) with no new safety events identified were identified during Year 8 and no patients returning to continuous Factor IX prophylaxis.10
In a Phase IIb study of adults (n=3) with haemophilia B receiving a single dose of etranacogene dezaparvovec, mean aPTT-based actor IX activity remained stable from Year 1 (40.7%) up to Year 5 (46.7%) and mean ABR for the cumulative follow-up was 0.14 (Years 0-5) for all bleeds. A favourable safety profile was maintained over 5 years.11 Despite the limited population size, these data may provide further evidence of the long-term effects of etranacogene dezaparvovec.10,11
About CSL
CSL (ASX:CSL) is a leading global biopharma company with a dynamic portfolio of lifesaving medicines, including those that treat haemophilia and immune deficiencies, vaccines to prevent influenza, and therapies in iron deficiency, dialysis and nephrology. Since our start in 1916, we have been driven by our promise to save lives using the latest technologies. Today, CSL – including our three businesses, CSL Behring, CSL Seqirus and CSL Vifor – provides lifesaving products to patients in more than 100 countries and employs 29,000+ people. Our unique combination of commercial strength, R&D focus and operational excellence enables us to identify, develop and deliver innovations so our patients can live life to the fullest. For inspiring stories about the promise of biotechnology, visit CSL.com/Vita.
For more information about CSL, visit CSL.com.
Media Contacts
Stephanie Fuchs, CSL
Mobile: +49 151 58438860
Email: Stephanie.Fuchs@cslbehring.com
Etanjalie Ayala, CSL
Mobile: +1 610 297 1069
Email: etanjalie.ayala@cslbehring.com
References:
1. Srivastava A, Santagostino E, Dougall A, et al. WFH Guidelines for the Management of Hemophilia, 3rd edition. Haemophilia 2020; 26 Suppl 6: 1-158.
2. Krumb E, Hermans C. Living with a "hemophilia-free mind" - The new ambition of hemophilia care? Res Pract Thromb Haemost 2021; 5: e12567.
3. Hermans C, Pierce GF. Towards achieving a haemophilia-free mind. Haemophilia 2023; 29: 951-953.
4. Pipe SW, Leebeek FWG, Recht M, et al. Gene Therapy with Etranacogene Dezaparvovec for Hemophilia B. N Engl J Med 2023; 388: 706-718.
5. Spronck EA, Liu YP, Lubelski J, et al. Enhanced Factor IX Activity following Administration of AAV5-R338L "Padua" Factor IX versus AAV5 WT Human Factor IX in NHPs. Mol Ther Methods Clin Dev 2019; 15: 221-231.
6. Thornburg CD. Etranacogene dezaparvovec for hemophilia B gene therapy. Ther Adv Rare Dis 2021; 2: 26330040211058896.
7. Pipe S, van der Valk P, Verhamme P, et al. Long-Term bleeding protection, sustained FIX activity, reduction of FIX consumption and safety of hemophilia B gene therapy: results from the HOPE-B Trial 3 years after administration of a single dose of etranacogene dezaparvovec in adult patients with severe or moderately severe hemophilia B. Blood 2023; 142: 1055.
8. Leebeek FWG, von Drygalski A, et al. The phase 3 HOPE-B trial shows 4-year durability of sustained near-normal FIX activity, bleed protection and favourable safety in adults with severe or moderately severe haemophilia B. EAHAD 2025. EAHAD25-ABS-1255.
9. Genezen MA, Inc. CSL Behring GmbH. Hemgenix® (etranacogene dezaparvovec): Summary of Product Characteristics [online]. Available at: https://www.ema.europa.eu/en/documents/product-information/hemgenix-epar-product-information_en.pdf [Last accessed: December 2025].
10. Leebeek FWG, Meijer K, Coppens M, et al. Stable Factor IX Expression and Sustained Reductions in Factor IX Use 8 Years after Gene Therapy with CSL220 (Formerly AMT-060) in Adults with Hemophilia B. Blood 2024; 144: 3578-3578.
11. von Drygalski A, Giermasz A, Gomez E, et al. OC 02.3 Etranacogene dezaparvovec hemophilia B gene therapy phase 2b trial final Results: stable and durable FIX level expression over 5 years. ISTH 2024 Oral Communication Abstracts. Research and Practice in Thrombosis and Haemostasis 2024; 8: 116.
INT-HGX-0045
