The Danish Medicines Council recommends CSL Behring’s gene therapy HEMGENIX® for adults with severe or moderately severe haemophilia B

COPENHAGEN, DENMARK – June 24, 2024 – Global biotechnology leader CSL Behring (ASX: CSL) today announced that a positive recommendation for reimbursement of HEMGENIX^® (etranacogene dezaparvovec) has been released by the Danish Medicines Council for the treatment of patients with rare blood clotting disorder, haemophilia B opening the way to finalize a commercial contract with Amgros, the Danish procurement authority.¹ Denmark is the first country in the Nordics to reimburse HEMGENIX^®.

HEMGENIX^® is the first one-time gene therapy approved in Denmark for the treatment of severe and moderately severe haemophilia B (congenital factor IX deficiency) in adult patients without a history of factor IX inhibitors.²This approval will advance the shift away from lifelong intravenous factor IX infusions, which can significantly impact the quality of life and wellbeing of patients.³

“Patients with haemophilia B are vulnerable to bleeds in joints, muscles, and soft tissues. Until now, patients with severe and moderately severe haemophilia B have required lifelong bleeding prophylaxis and treatment of breakthrough bleeds with repeated intravenous Factor IX infusions at regular intervals of 3 to 14 days. The bleeding tendency is sufficiently managed on this treatment schedule, but the repeated intravenous self-administration has a negative impact on patients’ quality of life and sense of identity. The one-dose gene therapy regimen has proven itself as steady long-term prophylaxis and will be an interesting kit in our toolbox over the next years,” said MD Peter Kampmann, Head of Department Hematology at Rigshospitalet, Copenhagen. “The approval of a gene therapy product in Denmark is a milestone. To the haemophilia society, the one-dose long term prophylaxis is a potential step away from the identity and the burden of chronic disease. To healthcare professionals, gene therapy in haemophilia is a herald to development and approval of other ATMPs to come.”

The Danish Medicines Council, Amgros and CSL Behring collaborated to develop an innovative agreement, suitable with the newly created Danish ATMP approvals process, and paving the way for access to future ground-breaking therapies for Danish patients. CSL Behring is working diligently with relevant stakeholders to continue the expansion of access to HEMGENIX^® in other Nordic countries and across Europe, following other milestone access pathways in France and Austria.⁴

“At CSL Behring, we are dedicated to developing and delivering innovative medicines and treatment options that improve the lives of people with bleeding disorders. This agreement is an important milestone for Danish people living with haemophilia B, as well as their friends, families and caregivers,” said Lise Grove, General Manager Denmark and Iceland, CSL Behring. “The Danish Medicines Council’s recommendation of HEMGENIX^® means that this groundbreaking gene therapy can now be provided to eligible patients, and we are hopeful that its value will continue to be recognised in other Nordic countries.”

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.

About HEMGENIX^®

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^®.⁵Fifty-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 2x10¹³ 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 17^th Annual Congress of the European Association for Haemophilia and Allied Disorders (EAHAD) 2024 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. HEMGENIX^® demonstrated 38.6% mean Factor IX activity levels sustained at three years, 64% reduction in annual bleed rate (ABR) versus routine Factor IX prophylaxis in the lead-in period, and 94% of patients discontinued Factor IX prophylaxis and remained prophylaxis-free three years post-treatment.⁶

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.

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Media Contacts Nordic Region

Lise Grove, General Manager Denmark and Iceland

Mobile: +45 29171638

Email: Lise.Grove@cslbehring.com

Fredrik Sjöö, MD, PhD, Head of Medical Affairs, Nordic Region

Mobile +46 (0) 70 418 9305

Email: Fredrik.Sjoeoe@cslbehring.com

Media Contacts Europe

Stephanie Fuchs

Mobile: +49 151 584 388 60

Email: Stephanie.Fuchs@cslbehring.com

References

1. Medicinrådet anbefaler genterapien Hemgenix efter ny effektbaseret prisaftale (medicinraadet.dk) [Accessed June 2024].

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 May 2024].

3. Srivastava A et al. WFH Guidelines for the Management of Hemophilia, 3rd edition. Haemophilia 2020; 26(Suppl 6):1-158.

4. https://www.cslbehring.de/en-us/news/2024/pm-hemgenix-agreement-austria; https://www.cslbehring.de/en-us/news/2023/pm-hemgenix-direct-access-f

5. Coppens M et al. Etranacogene dezaparvovec gene therapy for haemophilia B (HOPE-B): 24-month post-hoc efficacy and safety data from a single-arm, multicentre, phase 3 trial. The Lancet Haematology 2024; 11(4):E265-E275.

6. Pipe S et al. Oral presentation at EAHAD congress 2024.

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