July 31, 2014: Accelerated Review Demonstrates the Importance of Lenvatinib for This Therapeutic Area
FOR EU MEDIA ONLY: NOT FOR SWISS MEDIA
The European Medicines Agency (EMA) has approved Eisai’s request for accelerated assessment of the investigational oral multiple receptor tyrosine kinase (RTK) inhibitor lenvatinib, for the treatment of patients with progressive radioiodine-refractory, differentiated thyroid cancer (RR-DTC). Lenvatinib is expected to be filed imminently and could become a first in a new class of tyrosine kinase inhibitors.
Thyroid cancer is the most common endocrine malignancy. In Europe alone, over 50,000 cases of thyroid cancer were diagnosed in 2012. Although treatment is possible for most types of thyroid cancer, there remains an unmet need for treatment options once the disease has progressed.
Lenvatinib is an oral multiple receptor tyrosine kinase (RTK) inhibitor with a novel binding mode that selectively inhibits the kinase activities of vascular endothelial growth factor receptors (VEGFR), in addition to other proangiogenic and oncogenic pathway-related RTKs including fibroblast growth factor receptors (FGFR), the platelet-derived growth factor (PDGF) receptor PDGFRα, KIT and RET that are involved in tumour proliferation. This potentially makes lenvatinib a first-in-class treatment, especially given that it simultaneously inhibits the kinase activities of FGFR as well as VEGFR.,, Lenvatinib received orphan drug designation (ODD) for the treatment of follicular and papillary thyroid cancer from the European Commission inApril 2013.
“We are delighted that lenvatinib will undergo accelerated assessment by the EMA. The EMA recognises that RR-DTC is a challenging disease to treat and there is an urgent need for effective treatment options. At time of filing we will be another step closer to providing an innovative therapy to people with advanced thyroid cancer,” said Gary Hendler, President & CEO Eisai EMEA and President, Eisai Oncology Global Business Unit.
The EU marketing authorisation application will be based on the results of the Phase III SELECT (Study of (E7080) LEnvatinib in Differentiated Cancer of the Thyroid) trial of lenvatinib which showed that, progression free survival (PFS) with lenvatinib was extended significantly compared to placebo (Hazard Ratio (HR)=0.21, [99% CI, 0.14-0.31]; p<0.0001). The median PFS with lenvatinib and placebo were 18.3 months and 3.6 months, respectively.
The SELECT study was a multicentre, randomised, double-blind, placebo-controlled Phase III study to compare the PFS of patients with RR-DTC and radiographic evidence of disease progression within the prior 13 months, treated with once-daily, oral lenvatinib versus placebo. Secondary endpoints of the study included overall response rate (ORR), overall survival (OS) and safety. 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. Eisai hopes to receive file application in the next few months.
The development of lenvatinib underscores Eisai’s human health care mission, the company’s commitment to innovative solutions in disease prevention, cure and care for the health and wellbeing of people worldwide. Eisai is committed to the therapeutic area of oncology and addressing the unmet medical needs of patients and their families.
Notes to Editors
Lenvatinib, discovered and developed by Eisai, is an oral multiple receptor tyrosine kinase (RTK) inhibitor with a novel binding mode that selectively inhibits the kinase activities of vascular endothelial growth factor receptors (VEGFR), in addition to other proangiogenic and oncogenic pathway-related RTKs including fibroblast growth factor receptors (FGFR), the platelet-derived growth factor (PDGF) receptor PDGFRα, KIT and RET that are involved in tumour proliferation., This potentially makes lenvatinib a first-in-class treatment, especially given that it simultaneously inhibits the kinase activities of FGFR as well as VEGFR. It is currently under investigation as a treatment for thyroid, hepatocellular carcinoma (Phase III), non-small cell lung cancer (Phase II) and other solid tumour types.
About SELECT 
The SELECT (Study of (E7080) LEnvatinib in Differentiated Cancer of the Thyroid) study was a multicentre, randomised, double-blind, placebo-controlled Phase III study to compare the PFS of patients with RR-DTC 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 five most common lenvatinib treatment-related adverse events (TRAEs) of any grade were hypertension (67.8%), diarrhea (59.4%), 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. It is more common in women than in men and most are in their 40s or 50s at time of diagnosis.  Thyroid cancer is the most common endocrine malignancy and global figures show that its incidence has increased significantly over the last 50 years. 
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).While most DTC patients are curable with surgery and radioactive iodine treatment, the prognosis for those patients who do not respond is poor. There are limited treatment options for this difficult-to-treat, life-threatening and treatment-refractory form of thyroid cancer.
Eisai in Oncology
Our commitment to meaningful progress in oncology research, built on scientific expertise, is supported by a global capability to conduct discovery and preclinical research, and develop small molecules, therapeutic vaccines, and biologic and supportive care agents for cancer across multiple indications.
Eisai is one of the world’s leading research and development (R&D) based pharmaceutical companies and 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 human health care (hhc).
Eisai concentrates its R&D activities in three key areas:
- Oncology including: anticancer therapies; tumour regression, tumour suppression, antibodies, etc
- Neuroscience, including: Alzheimer’s disease, epilepsy, pain and weight management
- Vascular/Immunological reaction including: thrombocytopenia, rheumatoid arthritis, psoriasis, inflammatory bowel disease
With operations in the U.S., Asia, Europe and its domestic home market of Japan, Eisai employs more than 10,000 people worldwide. From its EMEA Knowledge Centre in Hatfield, UK, Eisai has recently expanded its business operations to includeEurope, the Middle East, Africa, Russia and Oceania (EMEA). Eisai EMEA has sales and marketing operations in over 20 markets, including Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Iceland, Ireland, Italy, the Middle East, the Netherlands, Norway, Portugal, Russia, Slovakia, Spain, Switzerland, Sweden, and the United Kingdom.
For further information please visit our web site: http://www.eisai.co.uk
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