First patients treated with HEMGENIX® (etranacogene dezaparvovec) gene therapy for haemophilia B in Denmark

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COPENHAGEN, DENMARK — 21 January 2025 — CSL Behring Denmark today announced that the first Danish patients with haemophilia B were treated with the gene therapy HEMGENIX® (etranacogene dezaparvovec).

HEMGENIX® is the first one-time gene therapy to be approved in Europe for the treatment of adults with severe and moderately severe haemophilia B, an inherited bleeding disorder caused by the lack of Factor IX (a protein needed to produce blood clots to stop bleeding). It is used in adults without a history of Factor IX inhibitors.1

 “The first patients in Denmark to receive HEMGENIX® (etranacogene dezaparvovec) mark a historic moment. Seventy-two years ago, it was discovered that inherited haemophilia B is caused by a genetic defect that deprives the liver of the capacity to produce enough functional Factor IX. Today, treating haemophilia B by restoring this capacity to the liver has become part of clinical practice in Denmark. This means that recurring factor-concentrate injections, repeated numerous times, can be replaced by a single infusion delivering the gene,” said Fredrik Sjöö, MD, PhD, Head of Medical Affairs, Nordic Region, CSL Behring. “This is what scientific progress in medicine is intended to achieve: improving the life of patients, in particular those with rare diseases, by providing innovative therapeutic options.”

Patients in Denmark can access HEMGENIX® through an innovative outcome-based agreement with Amgros, finalised in October 2024.2 This makes Denmark the first Nordic and European country to adopt a performance-based model, where costs are incurred only as long as the gene therapy proves effective over the agreed long-term period.

HEMGENIX® was granted conditional marketing authorisation by the European Commission (EC) for the European Union and European Economic Area in February 2023, following approval from the U.S. Food and Drug Administration (FDA) in November 2022. It has also been approved by Health Canada, the UK’s Medicines and Healthcare products Regulatory Agency (MHRA), Switzerland’s Swissmedic, and Australia’s Therapeutic Goods Administration (TGA).

Following these approvals, CSL Behring is working with relevant stakeholders to continue making HEMGENIX® available across Europe, building on milestone access decisions in Spain, Denmark, the UK (including Scotland), and Austria, so that more patients are able to receive the treatment.2-6

 

  

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.7 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.7

 

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.8 It uses a non-infectious viral vector derived from an adeno-associated virus (AAV5).8 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.9 These genetic instructions remain in the target cells, but generally do not become a part of a person’s own DNA.8 Once delivered, the new genetic instructions allow the cellular machinery to produce stable levels of Factor IX.10

 

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.11 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).11 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 AAV5.11

 

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.1,8,12 A total of 94% of patients (51/54) discontinued routine Factor IX prophylaxis and remained prophylaxis-free at 3 years post-treatment. Etranacogene dezaparvovec demonstrated mean Factor IX activity levels of 38.6%, which were sustained at 3 years, as well as a 64% annualised bleeding rate (ABR) reduction in all bleeds during months 7–36 post-treatment compared with routine Factor IX prophylaxis.1,8,12 The results also showed that etranacogene dezaparvovec is clinically effective in eligible patients with pre-existing AAV5 NAbs (up to a NAb titre of 1:898 or equivalent).1,8,12

 

Of the adverse events reported at 36 months post-infusion, 541 (76%) were mild, 137 (19%) were moderate and 31 (4%) were severe. No serious treatment-related adverse reactions were reported.1,8,12 One death resulting from urosepsis and cardiogenic shock in a 77-year-old patient at 65 weeks following dosing was considered unrelated to treatment by investigators and the company sponsor.12 A serious adverse event of hepatocellular carcinoma was determined to be unrelated to treatment with etranacogene dezaparvovec by independent molecular tumour characterisation and vector integration analysis.12 No inhibitors to Factor IX were reported.13

 

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.14 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).14

 

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 4.13 Despite the limited population size, these data provide further evidence of the long-term effects of etranacogene dezaparvovec.13,14

 

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

Stephanie Fuchs
Mobile: +49 151 584 388 60
Email: Stephanie.Fuchs@cslbehring.com

 

 

 

References

  1. uniQure, 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].
  2. Medicinrådet. The Medical Council recommends the gene therapy Hemgenix following a new effect-based price agreement. Available at: https://medicinraadet.dk/nyheder/2024/medicinradet-anbefaler-genterapien-hemgenix-efter-ny-effektbaseret-prisaftale. [Last accessed January 2025].
  3. CSL Behring. CSL Behring Signs First Commercial Agreement in Austria to Fund Haemophilia B Gene Therapy HEMGENIX®. Available at: https://www.cslbehring.de/en-us/news/2024/pm-hemgenix-agreement-austria. [Last accessed January 2025].
  4. National Institute for Health and Care Excellence. Final draft guidance: Etranacogene dezaparvovec for treating moderately severe or severe haemophilia B. Available at: https://www.nice.org.uk/guidance/gid-ta10699/documents/674. [Last accessed January 2025].
  5. Scottish Medicines Consortium. Etranacogene dezaparvovec (Hemgenix). Available at: https://scottishmedicines.org.uk/medicines-advice/etranacogene-dezaparvovec-hemgenix-full-smc2649/. [Last accessed January 2025].
  6. CSL Behring. CSL Behring granted positive reimbursement recommendation for Haemophilia B Gene Therapy, HEMGENIX® in Spain. Available at: https://www.cslbehring.de/en-us/news/2024/pm-hmgenix-reimbursement-spain [Last accessed January 2025].
  7. Srivastava A, Santagostino E, Dougall A, et al. WFH Guidelines for the Management of Hemophilia, 3rd edition. Haemophilia 2020; 26 Suppl 6: 1-158.
  8. Pipe SW, Leebeek FWG, Recht M, et al. Gene Therapy with Etranacogene Dezaparvovec for Hemophilia B. N Engl J Med 2023; 388: 706-718.
  9. 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.
  10. Thornburg CD. Etranacogene dezaparvovec for hemophilia B gene therapy. Ther Adv Rare Dis 2021; 2: 26330040211058896.
  11. 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.
  12. 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.
  13. 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.
  14. 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.



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