Additional Benefit of Orphan Drug, Lenvima® (lenvatinib) Determined by German Federal Joint Committee (G-BA)

- HATFIELD, England, December 21, 2015 /PRNewswire/ -- The German Federal Joint Committee (G-BA) has confirmed an additional patient-relevant therapeutic benefit for Lenvima® (lenvatinib) for the treatment of people with radioactive iodine refractory differentiated thyroid cancer (RAI refractory DTC). This decision follows the publishing of a benefit assessment report for lenvatinib on 1stOctober 2015. "Eisai is delighted about the favourable G-BA decision which successfully concludes the assessment of the additional benefit of lenvatinib for patients in Germany with RAI refractory DTC. Continued reimbursement in Germany for patients living with this difficult-to-treat cancer remains unaffected," commented Gary Hendler, President & CEO, Eisai EMEA and President, Eisai Oncology Global Business Unit. "The GBA's decision on the additional benefit of lenvatinib is a very important outcome especially when there are so few treatment options available in this setting," commented Professor Christoph Reuter, Clinic for Haematology, Haemostaseology and Oncology, Hannover Medical School. The benefit assessment for lenvatinib was based on data from the SELECT study which showed that lenvatinib significantly improves overall survival versus placebo in patients with progressive RAI Refractory-DTC (HR=0.53; 95% CI: 0.34, 0.82, nominal p=0.0051).1 The study enrolled 392 patients in over 100 sites in Europe, North and South America and Asia and was conducted by Eisai in collaboration with the SFJ Pharmaceuticals Group. 2 While thyroid cancer is relatively rare, over the past few decades the incidence of the disease is rising rapidly across the whole of Europe.3,4 In 2012 there were approximately 5,229 cases in Germany.3 More prevalent in women than men, at a ratio of 2 to 1, thyroid cancer is the most common endocrine malignancy.5 Lenvatinib has been approved for the treatment of refractory thyroid cancer in the United States, Europe Japan and Switzerland, and has been submitted for regulatory approval in South Korea, Canada, Singapore, Russia, Australia and Brazil. Lenvatinib was granted Orphan Drug Designation in Japan for thyroid cancer, in the United States for treatment of follicular, medullary, anaplastic, and metastatic or locally advanced papillary thyroid cancer and in Europe and Switzerland for follicular and papillary thyroid cancer Lenvatinib, discovered and developed by Eisai, is an oral molecular tri-specific targeted therapy that possesses a potent selectivity and a binding mode different to other tyrosine kinase inhibitors (TKI). Lenvatinib simultaneously inhibits the activities of several different molecules including vascular endothelial growth factor receptors (VEGFR), fibroblast growth factor receptors (FGFR), rearranged during transfection tyrosine kinase (RET), Tyrosinkinase KIT (KIT) and platelet-derived growth factor receptors (PDGFR). This potentially makes lenvatinib the first TKI that simultaneously inhibits the kinase activities of FGFR 1-4 as well as VEGFR 1-3.6 In addition, lenvatinib was found to have a new Type V binding mode of kinase inhibition that is distinct from existing compounds.7,8 The development of lenvatinib underscores Eisai's human health care (hhc) mission, the company's commitment to innovative solutions in disease prevention, cure and care for the health and well-being of people worldwide. Eisai is committed to the therapeutic area of oncology and to address the unmet medical needs of patients and their families. Notes to Editors     About Lenvatinib's Novel Binding Mode (Type V) 7,8 Kinase inhibitors are categorized into several types (Type I to Type V) depending on the binding site and the conformation of the targeted kinase in complex with them. Most of the currently approved tyrosine kinase inhibitors are either Type I or Type II, however according to X-ray crystal structural analysis, lenvatinib was found to possess a new Type V binding mode of kinase inhibition that is distinct from existing compounds. In addition, lenvatinib was confirmed via kinetic analysis to exhibit rapid and potent inhibition of kinase activity, and it is suggested that this may be attributed to its novel binding mode. About SELECT2    The SELECT (Study of (E7080) LEnvatinib in Differentiated Cancer of the Thyroid) study is a multicentre, randomised, double-blind, placebo-controlled Phase III study to compare the PFS of patients with radioactive iodine refractory differentiated thyroid cancer and radiographic evidence of disease progression within the prior 13 months, treated with once-daily, oral lenvatinib (24mg) versus placebo. The study enrolled 392 patients in over 100 sites in Europe, North and South America and Asia and was conducted by Eisai in collaboration with the SFJ Pharmaceuticals Group. Participants were stratified by age (≤65, >65 years), region and ≤1 prior VEGFR-targeted therapies and randomised 2:1 to either lenvatinib or placebo therapy (24mg/d, 28-d cycle). The primary endpoint was PFS assessed by independent radiologic review. The secondary endpoints of the study included overall response rate (ORR), overall survival (OS) and safety. Rates of complete response were 1.5% (4 patients) for the lenvatinib group and zero in the placebo group. The results for partial response were 63.2% (165 patients) in the lenvatinib group and 1.5% (2 patients) in the placebo arm. The median exposure duration was 13.8 months for lenvatinib and 3.9 months for placebo and the median time to response for lenvatinib was 2.0 months. Median OS has not yet been reached. The six most common lenvatinib treatment-related adverse events (TRAEs) of any grade were hypertension (67.8%), diarrhea (59.4%), fatigue (59.0%), decreased appetite (50.2%), weight loss (46.4%) and nausea (41.0%). TRAEs of Grade 3 or higher (Common Terminology Criteria for Adverse Events) included hypertension (41.8%), proteinuria (10.0%), weight loss (9.6%), diarrhoea (8.0%), and decreased appetite (5.4%). About Thyroid Cancer    Thyroid cancer refers to cancer that forms in the tissues of the thyroid gland, located at the base of the throat near the trachea.9 It is more common in women than in men and most are in their 40s or 50s at time of diagnosis.10 Thyroid cancer affects more than 52,000 people in Europe each year.3The incidence of thyroid cancer has increased significantly in the last decade by 69% and 65% in men and women, respectively.11 The most common types of thyroid cancer, papillary and follicular (including Hurthle cell), are classified as differentiated thyroid cancer (DTC) and account for approximately 90% of all cases.12 The remaining cases are classified as either medullary (5-7% of cases) or anaplastic (1-2% of cases).13 RAI Refractory-DTC is a rare, difficult-to-treat type of cancer, characterised by aggressive growth and spread. While most DTC patients are curable with surgery and radioactive iodine treatment, the prognosis for those patients who do not respond is poor.14 There are limited treatment options for this life-threatening and treatment-refractory form of thyroid cancer.13 About Eisai Co., Ltd.    Eisai Co., Ltd. is a leading global research and development-based pharmaceutical company headquartered in Japan. We define our corporate mission as "giving first thought to patients and their families and to increasing the benefits health care provides," which we call our human health care (hhc) philosophy. With over 10,000 employees working across our global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to realise our hhc philosophy by delivering innovative products in multiple therapeutic areas with high unmet medical needs, including Oncology and Neurology.  As a global pharmaceutical company, our mission extends to patients around the world through our investment and participation in partnership-based initiatives to improve access to medicines in developing and emerging countries. For more information about Eisai Co., Ltd., please visit http://www.eisai.com.   References