The National Institute for Health and Care Excellence (NICE) has published its positive recommendation for NHS England to fund HEMGENIX® (etranacogene dezaparvovec), through managed access under the Innovative Medicines Fund, as a treatment option for adults with severe and moderately severe haemophilia B (congenital factor IX deficiency) without a history of Factor IX (FIX) inhibitors.1
Etranacogene dezaparvovec is the first gene therapy to receive a positive recommendation from NICE through the Single Technology Appraisal process.
Eligible patients in England with severe and moderately severe haemophilia B, without a history of FIX inhibitors, could now benefit from access to this first, and currently only, single infusion gene therapy.1,2
This medicine is subject to additional monitoring. This will allow quick identification of new safety information.
HAYWARDS HEATH, ENGLAND – 27th June 2024 – CSL Behring announced that, following the Single Technology Appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) has recommended HEMGENIX® (etranacogene dezaparvovec) for immediate reimbursement by NHS England through a managed access agreement under the Innovative Medicines Fund (IMF). The first-of-its kind agreement will enable eligible patients to access the first and currently only gene therapy approved for haemophilia B in the UK.
This is a landmark for the UK Government’s Life Sciences Vision and represents a step forward in evaluating cell and gene therapies in the UK.
The decision confirms etranacogene dezaparvovec as:
- The first gene therapy to receive a positive recommendation through the STA process,
- The first product to receive a recommendation for managed access under the IMF3, and
- The first Advanced Therapy Medicinal Product (ATMP) to use an innovative outcomes-based payment model as described under the Voluntary Scheme for Branded Medicines Pricing, Access and Growth (VPAG).
The innovative outcome-based agreement reflects CSL Behring’s confidence in the efficacy and durability of this therapy as well as the value it adds to the health system. This agreement provides the NHS with the necessary assurance of value and financial protection to enable immediate funding to provide treatment for eligible patients.
"We are thrilled that NICE has honoured its commitment to a more progressive approach when assessing highly innovative medicines such as etranacogene dezaparvovec and this decision affirms the UK’s aspiration to be a leader in life sciences as outlined in the Government’s Life Sciences Vision,” said Eduardo Cabas, General Manager, CSL Behring UK and Ireland. “CSL Behring is proud to be a global leader in biotech innovation and we remain clearly committed to improving the lives of people living with rare genetic bleeding disorders – as demonstrated by this milestone for eligible haemophilia B patients in the UK and the NHS.”
Clive Smith, Chair of the Haemophilia Society, said: “This is a major step forward in the treatment options for people living with severe haemophilia B. It has the potential to significantly improve the quality of life of those who are eligible for such treatment. Gene therapy provides an opportunity for people to effectively eliminate painful bleeds, thereby improving joint health and allowing people to lead a full life, unrestricted by frequent infusions and trips to hospital.”
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. 456 More than 2,000 people live with haemophilia B in the UK, a proportion of whom will be eligible for consideration for gene therapy7. 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.5,8,9
Etranacogene dezaparvovec addresses the underlying genetic cause of haemophilia B10. It has demonstrated its potential as the first licensed gene therapy treatment option 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
Prof. Amit Nathwani, Professor of Haemophilia, University College London said: “The approval of access to etranacogene dezaparvovec in England marks a significant landmark for individuals with haemophilia B, offering a potentially transformative, long-term treatment option capable of improving the daily lives of eligible patients but also alleviating pressure on the NHS and dedicated healthcare professionals managing Haemophilia B.”
“The positive outcomes of the international HOPE-B Phase 3 trial underscores the potential for lasting clinical benefits with a single infusion of etranacogene dezaparvovec, heralding a new era in haemophilia B care.”
“With the UK's foundational contributions to haemophilia B gene therapy, this endorsement represents a pivotal step towards realising this community’s long-awaited access to innovative therapies.”
CSL Behring will work closely and collaboratively with the NHS England selected therapeutic centres to ensure that eligible patients can access treatment as soon as possible.
The Medicines and Healthcare products Regulatory Agency (MHRA) granted conditional marketing authorisation to HEMGENIX® (etranacogene dezaparvovec), as the first and only single infusion gene therapy for the treatment of severe and moderately severe haemophilia B (congenital FIX deficiency) in adults without a history of Factor IX (FIX) inhibitors in Great Britain (England, Scotland and Wales) in March 2023. A conditional marketing authorisation granted by the European Medicines Agency (EMA) in February 2023, applies to Northern Ireland. We are working determinedly with authorities in Wales, Scotland and Northern Ireland to ensure equity of access at the earliest opportunity for eligible patients across all nations of the UK.
About Haemophilia B4
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 dezaparvovec is 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). 10 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.12
About the HOPE-B Trial2,10
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 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 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 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 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.
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
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1 National Institute for Health and Care Excellence. Draft Guidance Consultation -
etranacogene dezaparvovec for treating moderately severe or severe haemophilia B
2 Pipe S.W., et al. Blood. 2023;142(Supplement 1):1055
3 NICE. Treatments under managed access. Available at: https://www.nice.org.uk/about/what-we-do/our-programmes/managed-access Last accessed June 2024
4 Srivastava A, et al. Haemophilia 2020;26(Suppl 6):1–158
5 Mannucci PM. Haematolgica 2020;105:545–553
6 Marchesini E, et al. Biologics. 2021; 15:221-235
7 United Kingdom Haemophilia Centres Doctors Organisation. UKHCDO Annual Report 2023 & Bleeding Disorder Statistics for the Financial Year 2022/23. https://www.ukhcdo.org/wp-content/uploads/2022/12/UKHCDO-Annual-Report-2022-2021-22-Data.pdf Last accessed: June 2024
8 Schrijvers L.H., et al. Br J Haematol 2016;174:454–460;
9 Thornburg C.D., et al. Patient Prefer Adherence 2017;11:1677–1686;
10 Pipe S. W. et al. 2023;388(8), 706–718.
11 Spronck EA et al. 2019;15:221-231.
12 Thornburg CD. Ther Adv in Rare Dis. 2021;2;1-14
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