Kyowa Kirin Responds to the National Institute for Health and Care Excellence (NICE) Decision to Not Provide People Living With Certain Rare Blood Cancers Access to POTELIGEO® (mogamulizumab)

Adults with two very rare forms of non-Hodgkin lymphoma will not have access to an innovative systemic treatment following NICE’s decision to not recommend mogamulizumab for routine use in the NHS. Kyowa Kirin is disappointed by this decision but remains committed to finding a resolution with NICE.

LONDON--(BUSINESS WIRE)--The National Institute for Health and Care Excellence (NICE) today published its final appraisal document (FAD) for POTELIGEO^® (mogamulizumab) announcing that POTELIGEO will not be made available on the NHS¹ in England and Wales. Mogamulizumab is a treatment for adults living with rare blood cancers, mycosis fungoides (MF) and Sézary syndrome (SS), two subtypes of Cutaneous T-Cell Lymphoma (CTCL), who have received at least one prior systemic therapy.² Kyowa Kirin is disappointed with this decision but remains committed to finding a solution for people living with MF and SS to have access to the medicine and will continue to work with NICE to find a resolution.

Richard Johnson, Northern Cluster General Manager, responsible for the UK at Kyowa Kirin, commented: “We are disappointed that, despite feedback from the patient and clinical community together with extensive evidence provided, the appraisal committee’s decision is negative. We fully support the recently published UK Rare Disease Framework and specifically priority 4 on “improving access to specialist care, treatments and drugs”. This is critically important given that many people with rare diseases, including those with CTCL, face challenges to access safe, high quality care and treatments.” He added: “Kyowa Kirin remains committed to supporting adults with MF and SS. The company will do all it can to ensure people with these debilitating haematological malignancies and eligible for these treatments have access to mogamulizumab.”

Professor Sean Whittaker, Professor of Cutaneous Oncology at the School of Basic and Medical Biosciences, Kings College London, and Consultant dermatologist, Guy's and St Thomas' NHS Foundation Trust, added: “MAVORIC is the largest randomised controlled trial completed in Cutaneous T-Cell Lymphoma, a rare form of non-Hodgkin's lymphoma, and the only trial to have included a significant proportion of patients with the advanced leukaemic stage of disease, Sézary syndrome, for which we have no consistently effective therapies. Patients with advanced stages of CTCL represent an unmet clinical need at present and effective therapies such as mogamulizumab are urgently needed to enable consolidation with stem cell transplantation. NICE's decision is very disappointing for patients with this rare malignancy.”

MF and SS are two forms of Cutaneous T-Cell Lymphoma (CTCL), which is a serious and potentially life-threatening form of cancer that affects the skin.³ People living with the condition have a substantially reduced quality of life.⁴ Additionally, there is a significant impact on quality of life for those caring for an individual living with CTCL.⁵ CTCL is treatable but not curable and there is a clear unmet need for new treatment options.

Stephen Scowcroft, Director of Operations and External Affairs at Lymphoma Action commented: “We are deeply disappointed by this decision and the effect it will have on people living with these rare and debilitating haematological cancers. We know that there is a real need for effective treatments for people living with mycosis fungoides and Sézary syndrome as there are currently limited treatment options and this can have a significant impact on a person’s quality of life, daily function and social interactions. We believe patients should have access to the best care and there continues to be a need for effective treatments for people living with mycosis fungoides and Sézary syndrome. We call on the relevant stakeholders, NICE and the company, to continue to discuss the options and to work with the patient community to find a resolution.”

About POTELIGEO^® (mogamulizumab)

Mogamulizumab is a first-in-class humanised monoclonal antibody (mAb) directed against CC chemokine receptor 4 (CCR4), a protein consistently expressed on cancerous cells seen in both MF and SS;^6,7,8 once mogamulizumab binds to CCR4, it increases attraction of immune cells from the immune system to destroy the cancerous cells.⁹

Mogamulizumab has been shown to offer benefits to many patients with MF and SS.¹⁰ The MAVORIC trial compared the efficacy of mogamulizumab with vorinostat in previously treated people with relapsed or refractory mycosis fungoides or Sézary syndrome, two types of Cutaneous T-cell lymphoma (CTCL).¹⁰ Patients taking mogamulizumab experienced control over their disease for more than twice as long as those taking the comparator treatment, vorinostat*¹ (7.7 months vs 3.1 months of median progression free survival), the primary endpoint of the trial.¹⁰ Levels of adverse events were similar between the two treatment groups.¹⁰

About Mycosis Fungoides (MF) and Sézary Syndrome (SS)

MF and SS are characterised by localisation of cancerous white blood cells called T lymphocytes (T cells), to the skin.^11,12 These cancerous T cells consistently express a protein called CC-chemokine receptor 4 (CCR4), which enables them to move from the blood to the skin.^6,7,8 When these cancerous T cells move to the skin, they can create a localised inflammatory immune skin response, commonly resulting in visible skin symptoms of red patches or plaques ^{6,13,14,15,16} which can resemble psoriasis or eczema.¹¹

MF and SS can affect the skin, blood, lymph nodes (part of the body’s immune system which is spread throughout the body) and internal organs.¹⁷ All four areas of the body are used to assess disease stage^18,19 and clinically significant involvement of the blood, particularly in more advanced disease, is linked with increased morbidity and an overall reduction in patient survival.^18,20,21

Due to its likeness to more common skin conditions such as eczema and psoriasis,¹¹ CTCL can take, on average, between 2 and 7 years for individuals to receive a confirmed diagnosis.²² It is critical for doctors to diagnose CTCL as early as possible as the patient’s prognosis can be affected if the disease progresses to later stages.²³ Whilst most individuals that present with early stage do not progress to a more severe stage,²⁴ patients with advanced disease have significantly poorer outcomes with only around half of patients (52%) surviving for just 5 years.¹⁸

CTCL is a rare disease that affects 0.7 per 100,000 patients across the UK.²⁵ The annual incidence of MF in Europe is estimated to be between 1 in 110,000 to 1 in 350,000.²⁶ The annual incidence of SS is 1 in 10,000,000.²⁷ Together they represent approximately 65% of all cases of CTCL.¹⁷

About Kyowa Kirin

Kyowa Kirin strives to create and deliver novel medicines with life-changing value. As a Japan-based Global Specialty Pharmaceutical Company with over 70-year heritage, we apply cutting-edge science including an expertise in antibody research and engineering, to address the needs of patients and society across multiple therapeutic areas including Nephrology, Oncology, Immunology/Allergy and Neurology. Across our four regions – Japan, Asia Pacific, North America and EMEA/International – we focus on our purpose, to make people smile, and are united by our shared values of commitment to life, teamwork/Wa, innovation, and integrity. You can learn more about the business of Kyowa Kirin at: https://www.kyowakirin.com.

¹* Vorinostat is a USA FDA-licensed existing treatment for MF and SS and is currently unlicensed in the EU

References

¹ NICE FAD on mogamulizumab for treating for previously treated mycosis fungoides and Sézary syndrome [ID1405]. Available from: https://www.nice.org.uk/guidance/indevelopment/gid-ta10305/documents

² POTELIGEO SMPC. Available from: https://www.ema.europa.eu/en/documents/product-information/poteligeo-epar-product-information_en.pdf Last Accessed: February 2021.

³ National Organization for Rare Disorders: Cutaneous T-Cell Lymphomas. Available from: https://rarediseases.org/rare-diseases/cutaneous-t-cell-lymphomas/. Last Accessed: February 2021.

⁴ Demierre MD, Gan S, Jones, J, Miller DR. Significant impact of cutaneous T‐cell lymphoma on patients' quality of life. Cancer. 2006;107(10):2504-2511.

⁵ Williams et al (2020) – Health state utilities associated with caring for an individual with CTCL. Journal of Medical Economics. 2020; 23(10):1142-1150.

⁶ Ferenczi K, Fuhlbrigge RC, Pinkus J, et al. Increased CCR4 expression in cutaneous T cell lymphoma. J Invest Dermatol. 2002;119:1405-10.

⁷ Yoshie O, et al. Frequent Expression of CCR4 in Adult T-Cell Leukemia and Human T-cell Leukemia Virus Type 1-transformed T cells. Blood. 2002;99(5):1505-11.

⁸ Ishida T, et al. Clinical Significance of CCR4 Expression in Adult T-cell Leukemia/Lymphoma: Its Close Association With Skin Involvement and Unfavorable Outcome. Clin Cancer Res. 2003;9:3625-34.

⁹ Duvic M, et al. Mogamulizumab for the treatment of cutaneous T-cell lymphoma: recent advances and clinical potential. Ther Adv Hematol. 2016;7(3):171-174.

¹⁰ Kim YH, Bagot M, Pinter-Brown L, et al. Mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma (MAVORIC): an international, open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2018;19(9):1192-1204.

¹¹ Cutaneous Lymphoma Foundation, Lymphoma Action and Lymphoma Coalition Europe. Cutaneous lymphoma – a patient’s guide. 2019. Available from: https://lymphoma-action.org.uk/sites/default/files/media/documents/2019-06/Cutaneous%20lymphoma%20-%20patient%26%23039%3Bs%20guide%20-%20English%20language%20source%20document%20-%20final%20version%20for%20publication%20-%20April%202019.pd Last accessed: February 2021.

¹² Mariani M, Lang R, Binda E, et al. Dominance of CCL22 over CCL17 in induction of chemokine receptor CCR4 desensitization and internalization on human Th2 cells. Eur J Immunol. 2004;34(1):231-240.

¹³ Wilcox RA. Cutaneous T-cell lymphoma: 2016 update on diagnosis, risk-stratification, and management. Am J Hematol. 2016;91(1):151-65.

¹⁴ Ni X, Jorgensen JL, Goswami M, et al. Reduction of regulatory T cells by Mogamulizumab, a defucosylated anti-CC chemokine receptor 4 antibody, in patients with aggressive/refractory mycosis fungoides and Sézary syndrome. Clin Cancer Res. 2014; 21(2):274-85.

¹⁵ Kakinuma T, Sugaya M, Nakamura K, et al. Hymus and activation-regulated chemokine (TARC/CCL17) in mycosis fungoides: serum TARC levels reflect the disease activity of mycosis fungoides. J Am Acad Dermatol. 2003;48(1):23-30.

¹⁶ Girardi M, Heald PW, Wilson LD. The Pathogenesis of Mycosis Fungoides. NEJM. 2004;350(19):1978-88.

¹⁷ Olsen E, Vonderheid E, Pimpinelli N, et al. Revisions to the staging and classification of mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC). Blood. 2007;110(6):1713-22.

¹⁸ Scarisbrick JJ, Prince M, Vermeer MH, et al. Cutaneous Lymphoma International Consortium Study of Outcome in Advanced Stages of Mycosis Fungoides and Sézary Syndrome: Effect of Specific Prognostic Markers on Survival and Development of a Prognostic Model. J Clin Oncol. 2015;33(32):3766-3773.

¹⁹ Willemze R, Hodak E, Zinzani PL et al. Primary cutaneous lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018;29(4):1-29.

²⁰ Kim EJ, Hess S, Richardson SK, et al. Immunopathogenesis and therapy of cutaneous T cell lymphoma. J Clin Invest. 2005;115(4):798-812.

²¹ Scarisbrick JJ, Whittaker, S, Evans, AV, et al. Prognostic significance of tumor burden in the blood of patients with erythrodermic primary cutaneous T-cell lymphoma. Blood. 2001;97(3):624-30.

²² CL Foundation: A Patient’s Guide. Available from: https://www.clfoundation.org/sites/default/files/2018-04/a_patients_guide.pdf. Last Accessed: February 2021.

²³ Agar N, et al. Survival Outcomes and Prognostic Factors in Mycosis Fungoides/Sezary Syndrome: Validation of the Revised International Society for Cutaneous Lymphomas/European Organisation for Research and Treatment of Cancer Staging Proposal. J Clin Ocol. 2010;28(31):4730-4739.

²⁴ Krejsgaard T, Lindahl LM, Mongan NP, et al. Malignant inflammation in cutaneous T-cell lymphoma—a hostile takeover. Semin Immunopathol. 2017;39(3):269–282.

²⁵ Gilson D, et al. British Association of Dermatologists and UK Cutaneous Lymphoma Group guidelines for the management of primary cutaneous lymphomas 2018. British Journal of Dermatology. 2019; 180:496-526.

²⁶ Orphanet: Mycosis Fungoides. Available from: https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=2584. Last Accessed: February 2021.

²⁷ Orphanet: Sézary syndrome. Available from: https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=3162. Last Accessed: February 2021.

KKI/UK/CTCL/0043

Date of Preparation: February 2021

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Victoria Hayes
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Email: victoria.hayes@kyowakirin.com