- Takeda UK Ltd. is pleased to announce that NICE has recommended the use of LIVTENCITY? (maribavir) as a twice daily oral treatment for adult patients with post-transplant cytomegalovirus (CMV) infection and/or disease that is refractory (with or without resistance) to one or more prior therapies, within their final appraisal determination (FAD) published today.[i],[ii]
- CMV is a frequent complication after transplantation and can lead to serious morbidity, including rejection of Transplanted Organ and Failure of Graft, and in some cases mortality. [iii], [iv]
- LIVTENCITY is the first and only oral treatment that inhibits CMV-specific UL97 protein kinase and its natural substrates.[v]
LONDON, Dec. 8, 2022 /PRNewswire/ -- Takeda UK Ltd. today announced that the National Institute for Health and Care Excellence (NICE), the health technology appraisal body in England and Wales, has issued its Final Appraisal Determination (FAD) recommending LIVTENCITY? (maribavir) in line with its license, for the treatment?of cytomegalovirus (CMV) infection and/or disease that is refractory (with or without resistance) to one or more prior therapies, including ganciclovir, valganciclovir, cidofovir or foscarnet in adult patients who have undergone a hematopoietic stem cell transplant (HSCT) or solid organ transplant (SOT).ii This recommendation follows recent Marketing Authorisation granted by the Medicines and Healthcare products Regulatory Agency (MHRA) on 11th November 2022. LIVTENCITY will be made available on the NHS to eligible patients within 90 days, in line with NICE guidance.
Cytomegalovirus (CMV) infection can be a significant complication after transplantation[iii],[vi] and can lead to increased organ rejection and higher hospitalisation rates.[iv],[vii] Existing therapies to treat post-transplant CMV infections may demonstrate serious side effects or may fail to adequately suppress viral replication.[viii] Until today there have been no treatments recommended by NICE for treating CMV infection that is refractory or resistant to other treatments. CMV infections that are refractory or resistant to currently available antivirals are a major cause of morbidity and mortality among solid organ transplant (SOT) and allogeneic haematopoietic stem cell transplant (HSCT) recipients.[ix] Additionally, existing therapies may require or prolong hospitalisation due to administration and may be poorly tolerated.[x],[viii]
Rachel Miller, Lead Nurse of Anthony Nolan, a UK charity that provides donor grafts for hematopoietic stem cell transplantation and supports transplant and cell therapy patients through multidisciplinary research and patient advocacy, said, "CMV reactivation can have a significant impact for some post-transplant patients with weak immune systems. Often infections can persist over a prolonged period, resulting in patients having to stay in hospital for longer or managing repeated hospital visits. Patients who experience CMV reactivation tend to have a reduced quality of life, impacting recovery both physically and psychologically. This is why it's so important that new and effective therapeutic options are developed and made available to improve patients' outcomes."
In the United Kingdom, there are approximately over 4,700 solid organ transplant (SOT) procedures and over 1,700 allogeneic haematopoietic stem cell transplant (HSCT) procedures every year[xi], [xii]. CMV infection occurs in approximately 18% of SOT patients overall[xiii] and approximately 50% of allogeneic HSCT patients[xiii]. Current antiviral treatment options for post-transplant CMV infections have unfavourable toxicities, such as neutropenia or nephrotoxicity, that may impact patient care and transplant outcomes.[xiv] In the SOLSTICE trial fewer patients were seen to have these toxicities.[xv]
"Transplant patients with a weak immune system are particularly vulnerable to the risk of CMV infection. The infection itself can affect multiple organs, including the lungs, liver, kidney, stomach and eyes, causing severe damage and even loss of the transplanted organ", said, Dr Mark Harber, Consultant Nephrologist at the Royal Free London NHS Foundation Trust, UK. "Standard anti-CMV treatments are hampered by dose related toxicities and require a complex balancing act of dose adjustments to minimise adverse events such as nephrotoxicity. I welcome the approval of maribavir for patients with difficult to treat CMV infection. This new oral anti-CMV treatment which appears to have few significant side effects is a welcome addition to the options for treating this infection and has the potential to improve the outcome of many of these patients."
The NICE recommendation was based on the Phase 3 SOLSTICE trial, which evaluated the safety and efficacy of maribavir versus conventional antiviral therapies - ganciclovir, valganciclovir, cidofovir or foscarnet - for the treatment of adult HSCT and SOT recipients with resistant/ refractory CMV infection.[xv]
Commenting on the recommendation, Simon Meadowcroft, Country Medical Director, Takeda UK & Ireland, said, "We are delighted that NICE has chosen to make LIVTENCITY available via NHS England for patients who have received ether a haematopoietic stem cell transplant or an organ transplant, and are suffering from infection with the CMV virus which has not been successfully treated with currently available antiviral medicines. Infection with CMV, one of the most common and serious post-transplant infections, can have serious consequences for patients including potential failure of the transplanted organ. The availability of a new treatment option will make a real difference to this vulnerable group of patients."
Peter Wheatley-Price, Market Access & Pricing Director, Takeda UK & Ireland, said, "This is a great example of how Takeda UK and NICE have worked in partnership to get access for this therapy. We are pleased to build on our great working relationship with NICE to achieve this positive outcome."
Please refer to maribavir UK Summary of Product Characteristics (SmPC) for more information.
Notes to Editors
About LIVTENCITY (maribavir)
Maribavir, an?orally bioavailable?anti-CMV?compound, is?the first and only antiviral agent?that targets and inhibits the pUL97 protein kinase and its natural substrates.[v], [ii]
On 11thNovember 2022, the MHRA granted Marketing Authorization for LIVTENCITY (maribavir) for the treatment?of CMV infection and/or disease that is refractory (with or without resistance) to one or more prior therapies, including ganciclovir, valganciclovir, cidofovir or foscarnet in adult patients who have undergone a HSCT or SOT. LIVTENCITY is approved in this indication in the UK, the EU and EEA (European Economic Area), In November 2021, maribavir received U.S. Food and Drug Administration (FDA) approval, under the brand name LIVTENCITY for the treatment?of adults and paediatric patients (12 years of age or older and weighing at least 35 kg) with post-transplant cytomegalovirus (CMV) infection/disease that is refractory to treatment (with or without genotypic resistance) with ganciclovir, valganciclovir, cidofovir, or foscarnet. U.S., Canada, and Australia.ii Regulatory filings are underway with other health authorities worldwide.
About Takeda Pharmaceutical Company
Takeda Pharmaceutical Company Limited is headquartered in Japan and is a global, values-based, R&D-driven biopharmaceutical leader committed to translating science into highly-innovative medicines. Takeda focuses its R&D efforts on four therapeutic areas: Oncology, Gastroenterology (GI), Neuroscience and Rare Diseases. We also make targeted R&D investments in Plasma-Derived Therapies and Vaccines. We are focusing on developing highly innovative medicines that contribute to making a difference in people's lives by advancing the frontier of new treatment options and leveraging our enhanced collaborative R&D engine and capabilities to create a robust pipeline. Our employees are committed to improving quality of life for patients and to working with our partners in health care in approximately 80 countries and regions.
Additional information about Takeda UK Ltd. is available through its corporate website,
www.takeda.com/en-gb.
Important Notice
For the purposes of this notice, "press release" means this document, any oral presentation, any question-and-answer session and any written or oral material discussed or distributed by Takeda Pharmaceutical Company Limited ("Takeda") regarding this release. This press release (including any oral briefings and any question-and-answer in connection with it) is not intended to, and does not constitute, represent or form part of any offer, invitation or solicitation of any offer to purchase, otherwise acquire, subscribe for, exchange, sell or otherwise dispose of, any securities or the solicitation of any vote or approval in any jurisdiction.
References
[i] NICE. Final appraisal document: Available at: https://www.nice.org.uk/guidance/gid-ta10792/documents/final-appraisal-determination-document. Accessed December 2022.
[ii] Maribavir SmPC
[iii] Ramanan P, Razonable RR. Cytomegalovirus infections in solid organ transplantation: a review. Infection & Chemotherapy. 2013;45(3):260. doi:10.3947/ic.2013.45.3.260
[iv] Azevedo LS, et al. Cytomegalovirus infection in transplant recipients. Clinics. 2015;70(7):515-523. doi:10.6061/clinics/2015(07)09
[v] Avram S, et al. Novel drug targets in 2021. Nat Rev Discov. 2022;21(5):328-328.
[vi] El Chaer F, Shah DP, Chemaly RF. How I treat resistant cytomegalovirus infection in hematopoietic cell transplantation recipients. Blood. 2016;128(23):2624-2636. doi:10.1182/blood-2016-06-688432
[vii] Yong MK, Tio SY, Valentine J, et al. The Economic and Health Utilization Cost of Clinically Significant Cytomegalovirus Infection Following Allogeneic Hematopoietic Stem Cell Transplantation. Blood. 2019;134(Supplement_1):3437-3437. doi:10.1182/blood-2019-128227
[viii] Chemaly RF, Chou S, Einsele H, et al. Definitions of resistant and refractory cytomegalovirus infection and disease in transplant recipients for use in clinical trials. Clinical Infectious Diseases. 2019;68(8):1420-1426. doi:10.1093/cid/ciy696
[ix] Papanicolaou, G.A., et al., Maribavir for Refractory or Resistant Cytomegalovirus Infections in Hematopoietic-cell or Solid-organ Transplant Recipients: A Randomized, Dose-ranging, Double-blind, Phase 2 Study. Clinical Infectious Diseases, 2019;68(8):1255-64
[x] Martín-Gandul C, Pérez-Romero P, González-Roncero FM, et al. Clinical impact of neutropenia related with the preemptive therapy of CMV infection in solid organ transplant recipients. J Infect. 2014;69(5):500-506. doi:10.1016/j.jinf.2014.07.001
[xi] NHS Blood and Transplant. Organ Donation and Transplantation: Activity Report 2019/20. 2020; https://nhsbtdbe.blob.core.windows.net/umbraco-assets-corp/19220/activity-report-2019-2020.pdf. Accessed November, 2022
[xii] BSBMTCT Registry. BSBMTCT Registry: 2019 Annual Activity. British Society of Blood and Marrow Transplantation and Cellular Therapies 2019; https://bsbmtct.org/activity/2019/ Accessed November, 2022.
[xiii] NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE. SINGLE TECHNOLOGY APPRAISAL. Maribavir for treating refractory or resistant cytomegalovirus infection after transplant. https://www.nice.org.uk/guidance/gid-ta10792/documents/committee-papers Accessed November, 2022.
[xiv] Maffini E, Giaccone L, Festuccia M, Brunello L, Busca A, Bruno B. Treatment of CMV infection after allogeneic hematopoietic stem cell transplantation. Expert Rev Hematol. 2016;9(6):585-596. doi:10.1080/17474086.2016.1174571
[xv] Avery R, Alain S, Alexander B, et al. Maribavir for refractory cytomegalovirus infections with or without resistance post-transplant: results from a phase 3 randomized clinical trial. Clinical Infectious Diseases. Published online December 2, 2021. doi:doi.org/10.1093/cid/ciab988.
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