CSL Behring’s Gene Therapy HEMGENIX (etranacogene dezaparvovec): Four Years Post-Infusion Data Continue to Show Sustained Efficacy and Safety in Adults with Haemophilia B

• 94% of patients eliminated factor IX prophylaxis and remained free of continuous prophylaxis through four years post-treatment
• Mean factor IX activity levels were sustained at near normal levels of 37% through four years post-treatment, reinforcing the efficacy of HEMGENIX^® in the treatment of haemophilia B
• Phase 3 HOPE-B data showed that a one-time treatment with HEMGENIX^®provided long-term bleed protection as mean adjusted annualised bleeding rate (ABR) for all bleeds was reduced by approximately 90% from lead-in as compared to year four

MARBURG, GERMANY — February 7, 2025 — Global biotechnology leader CSL Behring (ASX:CSL) today announced the four-year results from the pivotal HOPE-B study confirming the long-term durability and safety of a one-time infusion of HEMGENIX^® (etranacogene dezaparvovec) for adults living with haemophilia B. In an oral presentation at the 18th Annual Congress of the European Association for Haemophilia and Allied Disorders (EAHAD), data showed that through four years, HEMGENIX^® continues to deliver elevated and sustained factor IX activity levels, can offer long-term and greater bleed protection compared to prophylactic treatment, can eliminate the need for routine factor IX prophylaxis, and maintains a favourable safety profile. Receiving conditional marketing authorisation from the European Medicines Agency (EMA) in 2023, HEMGENIX^® is the first gene therapy approved for the treatment of severe and moderately severe haemophilia B (congenital factor IX deficiency) in adult patients without a history of factor IX inhibitors. It is also the only approved gene therapy for haemophilia B that can treat adult patients with and without AAV5 neutralising antibodies thereby providing the potential for a greater number of eligible patients to be treated.

“Haemophilia 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, Professor of Pediatrics and Pathology, Laurence A. Boxer Research Professor of Pediatrics and Communicable Diseases, Pediatric Medical Director, Hemophilia and Coagulation Disorders Program Director, Special Coagulation Laboratory 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.”

In the Phase III, 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 who received HEMGENIX^®, 51 completed four years of follow-up. HEMGENIX^® produced 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 and 37.4 IU/dL (n=47) at year four post-infusion. In addition, mean adjusted annualised bleeding rate (ABR) for all bleeds was reduced by approximately 90% from lead-in (4.16, n=54) as compared to year four (0.40, n=51). Furthermore, joint bleeds were reduced from a mean ABR of 2.34 at lead-in to 0.09 during year four. In year four, 94% of patients remained free of continuous prophylaxis treatment. No patients returned to continuous prophylaxis between year three and year four.

There were no serious adverse events related to treatment with HEMGENIX^®. HEMGENIX^® was generally well-tolerated, with a total of 96 treatment-related adverse events (AEs), 92 (96%) of which occurred in the first six months post-treatment. 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).

“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 haemophilia B and improve quality of life by alleviating the burden of ongoing factor IX prophylactic treatment,” said Andres Brainsky, Vice President R&D Hematology at CSL. “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. We are proud to continue to provide life-changing treatment options to the haemophilia community.”

The multi-year clinical development of HEMGENIX^®was led by uniQure and sponsorship of the clinical trials transitioned to CSL after it licensed global rights to commercialise the treatment. Additionally, CSL established a post-marketing registry, which will be informative to all stakeholders and will generate additional evidence on the long-term safety, efficacy, and durability of gene therapy. HEMGENIX^®has also been approved by the U.S. Food and Drug Administration (FDA) and granted conditional marketing authorisation by the UK’s Medicines and Healthcare products Regulatory Agency (MHRA), as well as authorisation by Health Canada, Switzerland’s Swissmedic and provisional approval by Australia’s Therapeutic Goods Administration (TGA).

About Haemophilia B

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 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

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.² It uses a non-infectious viral vector derived from an adeno-associated virus (AAV5).² 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.³ These genetic instructions remain in the target cells, but generally do not become a part of a person’s own DNA.² Once delivered, the new genetic instructions allow the cellular machinery to produce stable levels of Factor IX.⁴

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.⁵ 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).⁵ 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 AAV5.⁵

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.^2,6,7

Additional trial data

AMT-060 has a similar structure to etranacogene dezaparvovec, differing only in a single amino acid substitution in the F9 gene. In a Phase I/II study, the durability of AMT-060 was assessed in two cohorts of adult patients with severe/moderately severe haemophilia B receiving different single-infusion doses.⁹ Mean Factor IX activity remained stable in both cohorts at 5 years (Cohort 1, n=5, 52 weeks: 4.4%, Year 5: 5.2%; Cohort 2, n=5, 26 weeks: 6.9%, Year 5: 7.4%), mean ABR was maintained from Years 1–5 (Cohort 1: 7.30–6.40; Cohort 2, 1.58–0.20).⁹

In a Phase IIb study of adults (N=3) with haemophilia B receiving a single dose of etranacogene dezaparvovec, mean Factor IX activity remained stable from Year 1 (n=3; 40.7%) up to Year 4 (n=2; 45%) and ABR for the cumulative follow-up period decreased from 0.22 at Year 3 to 0.17 at Year 4.⁸ Despite the limited population size, these data provide further evidence of the long-term effects of etranacogene dezaparvovec.^8,9

About CSL
CSL (ASX:CSL; USOTC:CSLLY) is a global biotechnology 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 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 32,000 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

Fredrik Sjöö, MD, PhD
Head of Medical Affairs, CSL Behring Nordic Region
Mobile +46 (0) 70 418 9305
Email: Fredrik.Sjoeoe@cslbehring.com

Stephanie Fuchs, CSL Behring
Mobile: +49 151 58438860
Email: Stephanie.Fuchs@cslbehring.com

EUR-HGX-0264

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. Pipe SW, Leebeek FWG, Recht M, et al. Gene Therapy with Etranacogene Dezaparvovec for Hemophilia B. N Engl J Med 2023; 388: 706-718.

3. 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.

4. Thornburg CD. Etranacogene dezaparvovec for hemophilia B gene therapy. Ther Adv Rare Dis 2021; 2: 26330040211058896.

5. 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.

6. 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: January 2025].

7. Pipe SW, van der Valk P, Verhamme P, et al. Etranacogene dezaparvovec shows sustained efficacy and safety in adult patients with severe or moderately severe haemophilia B 3 years after administration in the hope-B Trial [EAHAD 2024 Oral Abstract OR09]. Haemophilia. 2024; 30: 25.

8. von Drygalski A, Pipe SW, Giermasz A, et al. Stable and durable factor IX levels over 4 years after etranacogene dezaparvovec gene therapy administration in a Phase 2b trial in patients with haemophilia B [EAHAD 2024 Abstract PO038]. Haemophilia. 2024; 30: 25.

9. Miesbach W, Recht M, Key N, et al. Durability of Factor IX activity and bleeding rate in people with severe or moderately severe haemophilia B after long-term follow-up in the phase 1/2 Study of AMT-060, and phase 2b and phase 3 studies of etranacogene dezaparvovec (AMT-061). Hamostaseologie 2023; 43: S46-S47.