HATFIELD, England, September 27, 2015 /PRNewswire/ --
FOR EU MEDIA ONLY: NOT FOR SWISS OR AUSTRIAN MEDIA
New data also shows potential for a lenvatinib serum biomarker in metastatic renal cell carcinoma
Lenvima(R) (lenvatinib) significantly improves overall survival versus placebo in patients with progressive radioactive iodine refractory differentiated thyroid cancer (RAI Refractory-DTC) (HR=0.53; 95% CI: 0.34, 0.82, nominal p=0.0051). This updated analysis from the Phase III SELECT study will be presented in an oral session at the European Cancer Congress (ECC), Vienna, on Saturday 26 September at 10:30 CEST (Abstract No. 2805).
New data shows that regardless of the time it took RAI Refractory-DTC patients to achieve an objective response (either at the time of the first tumour assessment (initial responders) or thereafter (subsequent responders)), their progression free survival (PFS) remained the same (HR=1.73; 95% CI: 0.95-3.15, p=0.07) (Abstract No. 2862). A third abstract to be presented at ECC concludes that irrespective of a patient's RAI Refractory-DTC inclusion criteria (either no 131I uptake, disease progression or extensive 131I exposure) lenvatinib improved PFS in all groups compared to placebo and there were no between group differences in PFS (Abstract No. 2864).
"These encouraging survival data confirm lenvatinib's efficacy profile in this difficult to treat patient population," said Lori J. Wirth MD, abstract author and Assistant Professor of Medicine, Harvard Medical School and Massachusetts General Hospital.
"We are proud that these new data show lenvatinib's benefit to overall survival in this rare tumour type. Eisai are committed to addressing the needs of patients and their families in this difficult to treat cancer," said Gary Hendler, President and CEO Eisai EMEA and President, Eisai Oncology Global Business Unit
New analysis from the Phase II study of lenvatinib in metastatic renal cell carcinoma (mRCC) will also be presented at the Congress. The study, which was first presented at the American Society of Clinical Oncology (ASCO) meeting in May 2015, investigated lenvatinib in combination with everolimus, and the two therapies separately. New data shows that in both subgroups of people receiving treatment for mRCC, with either high or low baseline angiopoietin-2 (ANG2) levels, the combination of lenvatinib and everolimus prolonged progression free survival (PFS) compared to everolimus alone (HR=0.30; 95% CI 0.12-0.73, p=0.004 for low baseline ANG2 and HR=0.53; 95% CI 0.29-0.99; p=0.033 for high baseline ANG2). These results which examined potential prognostic and predictive biomarkers for lenvatinib, everolimus, and as a combination, are to be presented as a poster session on Saturday 26 September 2015 at 16:45 CEST (Abstract no. 432).
For those patients in the high baseline ANG2 subgroup who received a combination of lenvatinib and everolimus for the treatment of mRCC, an overall survival benefit is shown (HR=0.44 (0.23-0.82); p=0.008).
"These phase II data are interesting as they suggest potential for predicting how people with advanced renal cell cancer will respond to lenvatinib in combination with everolimus. It is also encouraging to see lenvatinib working in similar ways in a different tumour type as these data build on previous findings presented at ASCO earlier this year," said Dr Hilary Glen, Consultant Medical Oncologist, Beatson West of Scotland Cancer Centre, Scotland, UK.
"We are excited to share the results of this research, and believe they are testament to Eisai's unwavering commitment to the discovery and development of new, efficacious treatment options for patients with rare cancers. Lenvatinib, now proving its potential in a second rare cancer, is evidence of the power of our industry-leading research and development," commented Kenichi Nomoto PhD, President, Oncology Product Creation Unit at Eisai
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.
Lenvatinib received Marketing Authorisation from the European Commission in May 2015 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).
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. 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 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
Eisai is currently conducting clinical studies of lenvatinib in several types of cancer including hepatocellular carcinoma (Phase III), renal cell carcinoma (Phase II), non-small cell lung cancer (Phase II) and endometrial cancer (Phase II).
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 was a multicentre, randomised, double-blind, placebo-controlled Phase III study to compare the PFS of patients with 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 (less than or equal to65, >65 years), region and less than or equal to1 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 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.
Thyroid cancer affects more than 52,000 people in Europe each year. 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).
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.  There are limited treatment options for this life-threatening and treatment-refractory form of thyroid cancer.
About Renal Cell Carcinoma
Renal cell carcinoma (RCC) is the most common form of kidney cancer. The standard treatment for metastatic or advanced renal cell carcinoma is molecular targeted drug therapy, which is designed to interfere with the specific molecules necessary for tumour growth and progression. Despite this, it remains a disease for which patients have very few treatment options.
RCC originates in the lining of the proximal convoluted tubule, the very small tubes in the kidney that filter the blood and remove waste products. This form of cancer also arises from the cortical collecting ducts in addition to the proximal tubule. The only tumours of the kidney that are not included in the definition of RCC are tumours of the renal pelvis and ureters.
RCC accounts for approximately 90% of all kidney malignancies and represents an estimated 2-3% of all cancer cases, with the highest incidence occurring in Western countries. During the last two decades, until recently, there has been an annual 2% increase in incidence of the disease worldwide.
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.
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 .
1. Motzer R et al. Randomized phase 2 three-arm trial of lenvatinib (LEN), everolimus (EVE), and LEN+EVE in patients (pts) with metastatic renal cell carcinoma (mRCC). 51st ASCO Annual Meeting, Chicago, USA May 2015 Abstract No: 4506
2. Matsui J et al. Multi-kinase inhibitor E7080 suppresses lymph node and lung metastases of human mammary breast tumor MDA-MB-231 via inhibition of vascular endothelial growth factor-receptor (VEGF-R) 2 and VEGF-R3 kinase. Clin Cancer Res 2008 Sep 1;14(17) :5459-65.
3. Matsui J et al. E7080, a novel inhibitor that targets multiple kinases, has potent antitumor activities against stem cell factor producing human small cell lung cancer H146, based on angiogenesis inhibition. Int J Cancer. 2008;122(3):664-71.
4. Okamoto K, et al. Distinct Binding Mode of Multikinase Inhibitor Lenvatinib Revealed by Biochemical Characterization. ACS Med. Chem. Lett 2015;6:89-94
5. SmPC Lenvima (updated May 2015). Available at: http://www.medicines.org.uk/emc/medicine/30412 . Accessed: September 2015
6. Schlumberger M et al. Lenvatinib versus placebo in radioiodine refractory differentiated thyroid cancer. NEJM 2015; 372: 621-630. Available at http://www.nejm.org/doi/full/10.1056/NEJMoa1406470 Accessed: September 2015
7. Newbold K et al. Phase 3 study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT): Results and subgroup analysis of patients from Europe. Presented as a digital poster at ETA 2014.
8. Wirth L et al. 2015; Open-Label Extension Phase Outcomes of the Phase 3 Select Trial of Lenvatinib in Patients with 131I-Refractory Differentiated Thyroid Cancer. Endocrine Reviews; 36;2: Abstract 0R44-6. Available at: http://press.endocrine.org/doi/abs/10.1210/endo-meetings.2015.THPTA.6.OR44-6 Accessed: September 2015
9. Schlumberger M et al. Relationship Between Thyroid-Stimulating Hormone Levels and Outcomes from the Randomized, Double-Blind, Phase 3 Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT). Available at: https://endo.confex.com/endo/2015endo/webprogram/Paper20459.html Accessed: September 2015
10. National Cancer Institute at the National Institute of Health. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/thyroid/Patient/page1/AllPages#1 . Accessed: September 2015
11. Brito J et al. BMJ 2013; 347
12. Eucan. Thyroid Cancer Factsheet. Available at: http://eu-cancer.iarc.fr/EUCAN/Cancer.aspx?Cancer=35. Accessed: September 2015
13. Cancer Research UK. Thyroid cancer incidence statistics. Available at: http://www.cancerresearchuk.org/cancer-info/cancerstats/types/thyroid/incidence/uk-thyroid-cancer-incidence-statistics Accessed: September 2015
14. Gild M et al. Multikinase inhibitors: a new option for the treatment of thyroid cancer. Nature Reviews Endocrinology. 2011; 7: 617-624
15. Thyroid Cancer Basics. 2011. Available at: http://www.thyca.org . Accessed: September 2015
16. Pacini F et al. ESMO Guidelines Working Group. Ann Oncol. 2012;23(suppl 7) :vii110-vii119.
17. National Cancer Institue at the National Institute of Health. Available at: http://www.cancer.gov/types/kidney/patient/kidney-treatment-pdq . Accessed: September 2015
18. Ljungberg et al. Guidelines on Renal Cell Carcinoma. Available at: http://uroweb.org/wp-content/uploads/10-Renal-Cell-Carcinoma_LR-LV2-2015.pdf . Accessed: September 2015
Date of preparation: September 2015
Job code: Oncology-UK0047
CONTACT: Eisai, Cressida Robson / Ben Speller, +44(0)7908-314-155 /+44(0)7908-409416, Cressida_Robson@eisai.net / Ben_Speller@eisai.net; TonicLife Communications, Alex Davies / Emma Coughlan, +44(0)7720-496-472 /+44(0)7772-534-646, Alex.Davies@toniclc.com / Emma.Coughlan@toniclc.com