HATFIELD, England, June 9, 2015 /PRNewswire/ --
FOR UK MEDIA ONLY
Launch delivers important new treatment option for advanced thyroid cancer following significant progression-free survival data from the SELECT trial
Lenvima® (lenvatinib) launches in the UK today, a treatment option for people with radioactive iodine refractory differentiated thyroid cancer (RAI refractory DTC). Advanced thyroid cancer is a difficult to treat condition with a poor prognosis and lenvatinib represents a significant step forward for patients in the UK.
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Lenvatinib is indicated for the treatment of adult patients with progressive locally advanced or metastatic, differentiated (papillary, follicular, Hürthle cell) thyroid carcinoma (DTC), refractory to radioactive iodine (RAI).
"As a disease with few treatment options, the launch of lenvatinib in the UK helps address the significant medical need for those people living with this aggressive form of thyroid cancer. The data show lenvatinib's proven benefits in progression-free survival, which means patients will now have more time before their cancer progresses, something we know is incredibly important for people with an advanced cancer," commented Dr Kate Newbold, Consultant Clinical Oncologist at The Royal Marsden, London.
Lenvatinib demonstrates significantly prolonged progression-free survival (PFS) in RAI refractory DTC versus placebo. Lenvatinib shows a median 18.3 months progression free survival PFS versus 3.6 months for placebo (hazard ratio [HR] 0.21; 99% confidence interval 0.14-0.31, p<0.0001). In addition, the study underlines the rapid response of lenvatinib, with a median time to first objective response of two months. The SELECT study published in the New England Journal of Medicine is a randomised, double-blind, multicentre trial for people with progressive radioactive iodine refractory differentiated thyroid cancer (n=392). Lenvatinib significantly improves objective response rate versus placebo (64.8% versus 1.5%; p<0.0001). For lenvatinib, the most common treatment related adverse events were hypertension, diarrhoea, fatigue, decreased appetite, decreased weight, and nausea.
"This is welcome news for people in the United Kingdom living with advanced thyroid cancer for whom treatment options are currently very limited. The development of new targeted therapies such as lenvatinib gives us all a renewed sense of optimism and I look forward to patients in the UK being able to benefit from this new treatment," commented Judith Taylor, Lead Thyroid Cancer Group, British Thyroid Foundation.
"The launch of Lenvima represents great news for both Eisai and for patients who will now have access to this significant new treatment. Lenvima is a drug that was developed in the UK, will be manufactured in the UK and has now been launched first in the UK, something we at Eisai are very proud of," commented Gary Hendler, President & CEO Eisai EMEA and President, Eisai Oncology Global Business Unit.
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), RET, 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., In addition, lenvatinib was found to have a new Type V binding mode of kinase inhibition that is distinct from existing compounds.
Thyroid cancer incidence rates have increased in the UK over the past few decades. Although this type of cancer is relatively rare, numbers are rising and there are approximately 2,800 new cases in the UK each year.  More prevalent in women than men, at a ratio of 2 to 1, thyroid cancer is the most common endocrine malignancy.  Experts estimate that there are approximately 250 people in the UK living with RAI refractory DTC.
Lenvatinib has been approved for the treatment of refractory thyroid cancer in the United States, Europe and Japan, and has been submitted for regulatory approval in Switzerland, South Korea, Canada, Singapore, Russia, Australia and Brazil. Lenvima 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 for follicular and papillary thyroid cancer.
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)
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.
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%).
Subgroup analyses presented at the European Thyroid Association Annual Meeting in September 2014 showed that lenvatinib maintained a PFS benefit in all pre-defined subgroups of people with progressive radioiodine-refractory differentiated thyroid cancer. In particular, the PFS benefit observed in 195 people with progressive radioiodine-refractory differentiated thyroid cancer in Europe (lenvatinib n=131 and placebo n=64) was similar to the PFS of overall study population (HR=0.24, [95% CI, 0.16-0.35]). The median PFS with lenvatinib and placebo were 18.7 months and 3.7 months respectively.
Two recent subanalyses from the SELECT study have been presented at the Endocrine Society Congress 2015 (ENDO). The first reports the results of the open-label extension phase of SELECT and aims to assess the crossover of patients in the placebo arm to the optional open-label lenvatinib treatment period. The results highlight that patients who crossed over from the placebo arm achieved a median PFS of 12.4 months with open-label lenvatinib treatment. Although toxicities were substantial, these were generally managed with medications, dose interruption, and dose reductions.
The second abstract examines the relationship between thyroid abnormalities and their effect on the safety and efficacy outcomes in SELECT. The analysis shows that although an increase in thyroid-stimulating hormone (TSH) levels was a frequent complication, its direct relationship to lenvatinib therapy has not been established and there is no evidence TSH levels affect tumour responses to lenvatinib treatment.
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. It is more common in women than in men and most are in their 40s or 50s at time of diagnosis.
The incidence of thyroid cancer has increased significantly in the last decade by 69% and 65% in men and women, respectively. 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. The remaining cases are classified as either medullary (5-7% of cases) or anaplastic (1-2% of cases).
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.
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Date of preparation: June 2015
Job code: Lenvatinib-UK0052