Eligible patients in Scotland with severe and moderately severe haemophilia B, without a history of FIX inhibitors, could now benefit from access to this first available, single infusion gene therapy [1],[2]
Following the recommendation from the National Institute for Health and Care Excellence (NICE) in July 2024, today’s acceptance from the SMC means that eligible patients across the UK may now access etranacogene dezaparvovec [1],[3]
This medicine is subject to additional monitoring. This will allow quick identification of new safety information.
HAYWARDS HEATH, ENGLAND – 12th August 2024 – CSL Behring has announced that the Scottish Medicines Consortium (SMC) has accepted HEMGENIX® (etranacogene dezaparvovec) for use within NHS Scotland on an interim basis, until full marketing authorisation is granted.[1] The recommendation may enable eligible patients to access the first gene therapy approved for haemophilia B in Scotland.[4]
Alan Martin, Director, Haemophilia Scotland, said: “Today’s decision to recommend the use of etranacogene dezaparvovec marks a significant moment for the treatment of haemophilia B in Scotland. This new medicine has the potential to significantly improve the quality of life for those eligible by reducing the need for constant infusions. This could potentially enable them to live their lives and take part in activities previously denied to them with a reduced fear of bleeds or long-term joint damage.
This decision symbolises to the haemophilia community that the latest medical treatments and innovations will be made available to those who can benefit from them. We congratulate the Scottish Medicines Consortium and NHS Scotland for taking this positive step forward.”
Haemophilia B is a rare genetic bleeding disorder in which a gene mutation causes coagulant Factor IX (FIX), an important clotting protein, to be deficient or missing. The disease is characterised by bleeding episodes, pain, and long-term complications such as joint damage.[5],[6],[7]
Approximately 213 people live with haemophilia B in Scotland, a proportion of whom will be eligible for consideration for gene therapy.[8] Those with severe disease currently require lifelong treatment of intravenous FIX (FIX prophylaxis), which can still leave patients vulnerable to breakthrough bleeds and pain in the days before their next infusion.[4],[9],[10]
Prof Pratima Chowdhary, Consultant Haematologist & Chair, The United Kingdom Haemophilia Centre Doctors’ Organisation said: “The reimbursement of etranacogene dezaparvovec in Scotland is a much welcome decision for the clinical community. Given the advancement of gene therapies for haemophilia over the years, we may now be able to provide NHS Scotland patients with access to a potentially transformative treatment. Today marks the start of the ability to provide Scottish patients with the possibility to eliminate bleeds and improve their quality of life through one single infusion.”
Eduardo Cabas, General Manager, CSL Behring UK and Ireland, said: “The swift acceptance from the Scottish Medicines Consortium to reimburse etranacogene dezaparvovec is a clear signal that Scotland is putting itself at the forefront of the scientific innovation and recognition.
At CSL Behring, we have worked closely and collaboratively with health agencies, clinicians and patient advocates from across the UK to showcase the meaningful benefit of embracing highly innovative medicines, such as etranacogene dezaparvovec, and are especially grateful for the SMC’s agile and pragmatic approach when assessing this gene therapy. We now look forward to partnering with NHS Scotland and leading healthcare professionals from across the country to ensure eligible patients can access this landmark treatment when needed.”
This acceptance follows the decision on Wednesday 24th July from NICE to recommend the reimbursement of etranacogene dezaparvovec.[3] This confirmed the treatment as the first gene therapy to receive a positive recommendation through the Single Technology Appraisal process and the first product to receive a recommendation for managed access under the Innovative Medicines Fund.[11]
Etranacogene dezaparvovec addresses the underlying genetic cause of haemophilia B.[12] It has demonstrated its potential as the first licensed gene therapy for severe or moderately severe haemophilia B to significantly reduce the rate of annual bleeds with a single infusion, potentially reducing or eliminating the need for routine infusions, currently administered every 3-21 days.[2]
The therapeutic benefit of etranacogene dezaparvovec is supported by data from the Phase III HOPE-B study, the largest gene therapy study in haemophilia B to date. The data show that a single infusion of etranacogene dezaparvovec demonstrated significant increases in mean FIX activity levels of 36.9% at 18-months, which were sustained at 36.7% at 24-months and 38.6% at 36-months.[2] This increase in mean FIX activity led to an adjusted annualised bleed rate (ABR) reduction of 64% at 24 and 36-months post-dose compared to the 6-month lead-in period where patients were on stable prophylactic infusions.[2]
Following infusion of etranacogene dezaparvovec, 94% of patients in the HOPE-B study discontinued routine FIX prophylaxis, meaning they no longer required regular infusions for up to 36 months.[2] Of the adverse events reported 36 months post-infusion, 541 (76%) were mild, 137 (19%) were moderate and 31 (4%) were severe. [2] The HOPE-B trial has now completed four years of follow up [2]
About Haemophilia B[5]
Haemophilia B is a life-threatening rare disease caused by a mutation on the F9 gene, resulting in low levels of functional clotting factor IX. 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 FIX to temporarily replace or supplement low levels of the blood-clotting factor.
About etranacogene dezaparvovec
Etranacogene dezaparvovecis a gene therapy that reduces the rate of abnormal bleeding in eligible people with severe or moderately severe 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). [14] 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. [13] 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.[14]
About the HOPE-B Trial [2],[14]
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. Fifty-four adult hemophilia 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 at least the six-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 neutralizing antibodies (NAbs) to AAV5.
A total of 54 patients received a single dose of etranacogene dezaparvovec 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.
Of the adverse events reported 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. One death (previously reported) 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 (also previously reported) was determined to be unrelated to treatment with etranacogene dezaparvovec by independent molecular tumor characterisation 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 etranacogene dezaparvovec and the ongoing possible benefit this treatment may offer people living with haemophilia B.
About CSL
CSL Limited is a global biotechnology company with a dynamic portfolio of essential 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.
Media contacts:
Tony Bridger
Digital and PR Manager, UK and Ireland
CSL Behring
Mobile: +447880383198
Email: tony.bridger@cslbehring.com
Nathan McGlone
Associate Director and Media Lead
Aurora Healthcare Communications
Mobile: +44 7506734401
Email: nathan.mcglone@auroracomms.com
References
[1] SMC Acceptance
[2] Pipe S.W., et al. Blood. 2023;142(Supplement 1):1055
[3] National Institute for Health and Care Excellence. Etranacogene dezaparvovec for treating moderately severe or severe haemophilia B [ID3812]. Final Draft Guidance. July 2024
[4] SMC. Medicines advice. Available at: https://scottishmedicines.org.uk/medicines-advice/?active-tab=0&node-id=6990&keywords=haemophilia+B&filter-3561=&filter-3567=&filter-3803=&from=&to=&total-results-0=1&total-results-1=0 Last accessed: August 2024
[5] Srivastava A, et al. Haemophilia 2020;26(Suppl 6):1–158
[6] Mannucci PM. Haematolgica 2020;105:545–553
[7] Marchesini E, et al. Biologics. 2021; 15:221-235
[8] United Kingdom Haemophilia Centres Doctors Organisation. UKHCDO Annual Report 2023 & Bleeding Disorder Statistics for the Financial Year 2022/23. Available at: https://www.ukhcdo.org/wp-content/uploads/2022/12/UKHCDO-Annual-Report-2022-2021-22-Data.pdf Last accessed: August 2024
[9] Schrijvers L.H., et al. Br J Haematol 2016;174:454–460;
[10] Thornburg C.D., et al. Patient Prefer Adherence 2017;11:1677–1686;
[11] NICE. Treatments under managed access. Available at: https://www.nice.org.uk/about/what-we-do/our-programmes/managed-access Last accessed August 2024
[12] Pipe S. W. et al. 2023;388(8), 706–718.
[13] Spronck EA et al. 2019;15:221-231.
[14] Thornburg CD. Ther Adv in Rare Dis. 2021;2;1-14
