Italy Approves Reimbursement of Innovative Gene Therapy HEMGENIX® (etranacogene dezaparvovec) for Haemophilia B

MILAN, July 31, 2025 – CSL Behring Italy today announced that on July 29, 2025 the Board of Directors of the Italian Medicines Agency (AIFA), approved the reimbursement of HEMGENIX^® (etranacogene dezaparvovec). HEMGENIX^® is the first one-time gene therapy for adults with severe and moderately severe haemophilia B (congenital Factor IX deficiency). AIFA recognised HEMGENIX^® as an innovative therapy.

This decision marks a key milestone in access to therapeutic innovation in Italy and offers eligible patients a new option in the management of their condition.

Haemophilia B is a rare and potentially life-threatening disease that causes serious, often spontaneous bleeding episodes affecting joints, muscles, and internal organs. Currently, patients require lifelong, ongoing infusions of Factor IX to prevent bleeding and manage their protein deficiency.

HEMGENIX^® offers a one-time treatment, allowing people living with haemophilia B to eliminate the need for regular Factor IX infusions, thereby offering patients the possibility of more freedom from prophylaxis and significantly improving their quality of life. HEMGENIX^® is administered as a single intravenous infusion and uses an adeno-associated virus (AAV) vector to deliver a functional gene into cells, enabling the liver to produce Factor IX autonomously and sustainably, helping to prevent or significantly reduce bleeding episodes.

“We are pleased that AIFA has recognized the value of HEMGENIX^®, offering a new therapeutic option to people living with haemophilia B in Italy,” said Oliver Schmitt, Managing Director of CSL Behring Italy. “This approval represents an important step toward a future in which patients can live with fewer limitations and greater peace of mind. Our commitment now is to work closely with health authorities to ensure that this innovation is made accessible quickly and equitably across the entire country.”

CSL Behring continues its commitment to expanding access to gene therapy across Europe and beyond, following recent positive reimbursement decisions in countries such as Spain, Switzerland, Germany, the UK (including Scotland), Denmark and Austria. Patients in most of these countries, including France, Denmark, Austria, Spain, the UK and Germany have already experienced treatment with HEMGENIX^®.

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 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

Etranacogene dezaparvovec was generally well-tolerated, with a total of 96 treatment-related adverse events (AEs) 4 years post-infusion, 92 (96%) of which occurred in the first six months post-treatment.⁸ No serious treatment-related adverse reactions were reported.^4,8,9 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.¹¹ Three previously reported serious adverse events (hepatocellular carcinoma, schwannoma and myelodysplastic syndrome) were determined to be unrelated to treatment with etranacogene dezaparvovec by independent molecular tumour characterisation and vector integration analysis.¹¹ No inhibitors to Factor IX were reported.⁸

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. 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: July 2025].
10. Klamroth R, Van der Valk P, Quon D, et al. Four- year results of etranacogene dezaparvovec in haemophilia B patients with pre-existing AAV5 neutralising antibodies: Phase 3 HOPE-B trial [EAHAD 2025 Abstract PO037] Haemophilia. 2025; 31(Suppl. 1):49.
11. 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.

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