MARBURG, GERMANY – December 13, 2023 – Global biotechnology leader CSL Behring (ASX: CSL) has been granted Direct Access for HEMGENIX® (etranacogene dezaparvovec) by the French Ministry of Health, marking the first treatment to be authorised by this innovative process in France1. HEMGENIX® is the first and only one-time gene therapy for the treatment of severe and moderately severe haemophilia B (congenital Factor IX deficiency) in adult patients without a history of Factor IX inhibitors2. Through Direct Access, appropriate people living with haemophilia B will now be able to access HEMGENIX®.
Patients with haemophilia B currently require lifelong treatment with intravenous Factor IX infusions, which can have a significant impact on quality of life and wellbeing3. According to the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA), there is an “unmet medical need for new therapeutic approaches that might free patients from the burden of frequent infusions, or episodically at the time of a bleeding event4.”
Following European marketing authorisation for HEMGENIX® in February 2023, CSL Behring submitted a request for Direct Access to the Ministry of Health in early October 2023. This is the first time a medicine has been accepted via this exceptional access scheme in France and paves the way for other European countries to implement innovative access solutions.
“We are delighted and grateful for this historic decision from the Ministry of Health to grant patients Direct Access to HEMGENIX® in France,” said Dr Lutz Bonacker, SVP and General Manager Commercial Operations Europe, CSL Behring. “It is hugely encouraging to see new pathways for access being explored, enabling eligible patients to receive gene therapy that could have a potentially transformative impact for them and their loved ones. This approval is an example of how effective collaboration and innovative thinking can deliver ground-breaking access solutions for patients across Europe, where there is still significant unmet patient need in haemophilia B.”
The Direct Access process is a two-year experimental measure, established by the French Social Security Financing Act (LFSS 2022). The programme allows treatments to be fully reimbursed by the French Health Insurance system for up to a year, following publication in the Official Journal.5
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. 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.
HEMGENIX® is a 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 deficient protein in haemophilia B. It uses AAV5, a non-infectious viral vector, called an adeno-associated virus (AAV). The AAV5 vector carries the Padua gene variant of Factor IX (FIX-Padua) to the target cells in the liver, generating factor IX proteins that are 5x-8x more active than normal. These genetic instructions remain in the target cells, but generally do not become a part of a person’s own DNA. Once delivered, the new genetic instructions allow the cellular machinery to produce stable levels of factor IX.
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 HEMGENIX®. Fifty-four adult haemophilia B patients classified as having moderately severe to severe haemophilia B and requiring prophylactic factor IX replacement therapy were enrolled in a prospective, six-month or longer observational period during which time they continued to use their current standard of care therapy to establish a baseline Annual Bleeding Rate (ABR). After the six-month lead-in period, patients received a single intravenous administration of HEMGENIX® at the 2x10^13 gc/kg dose. Patients were not excluded from the trial based on pre-existing neutralizing antibodies (NAbs) to AAV5.
A total of 54 patients received a single dose of HEMGENIX® in the pivotal trial, with 52 patients completing at least three years of follow-up. The primary endpoint in the pivotal HOPE-B study was ABR 52 weeks after achievement of stable factor IX expression (months 7 to 18) compared with the six-month lead-in period. For this endpoint, ABR was measured from month seven to month 18 after infusion, ensuring the observation period represented a steady-state factor IX transgene expression. Secondary endpoints included assessment of factor IX activity.
No serious treatment-related adverse reactions were reported. 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. A serious adverse event of hepatocellular carcinoma was determined to be unrelated to treatment with HEMGENIX® by independent molecular tumour characterization and vector integration analysis. No inhibitors to factor IX were reported.
Long-term three-year data presented at the 65th American Society of Hematology (ASH) 2023 Annual Meeting and Exposition continue to reinforce the potential long-lasting efficacy and safety of HEMGENIX® and the ongoing benefit of this treatment for people living with haemophilia B.
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.
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1 Republique Française. Légifrance: Article 62 of Law No. 2021-1754. Available at: https://www.legifrance.gouv.fr/jorf/id/JORFTEXT000048551003 [Accessed December 2023].
2 European Medicines Agency. First Gene therapy to treat haemophilia B. Available at: https://www.ema.europa.eu/en/news/first-gene-therapy-treat-haemophilia-b. [Accessed December 2023].
3 Srivastava A et al. WFH Guidelines for the Management of Hemophilia, 3rd edition. Haemophilia 2020; 26(Suppl 6):1-158.
4 European Medicines Agency. First Gene therapy to treat haemophilia B. Available at: https://www.ema.europa.eu/en/news/first-gene-therapy-treat-haemophilia-b. [Accessed December 2023].
5 Ministère de la Santé et de la Prévention. Dispositif d’accès direct pour certains produits de santé. Available at: https://sante.gouv.fr/soins-et-maladies/medicaments/professionnels-de-sante/autorisation-de-mise-sur-le-marche/article/dispositif-d-acces-direct-pour-certains-produits-de-sante#:~:text=L'objectif%20est%20de%20faire,compl%C3%A9ment%20de%20l'acc%C3%A8s%20pr%C3%A9coce [Accessed December 2023].