New Application of Lenvatinib in Combination with Everolimus for Unresectable Advanced or Metastatic Renal Cell Carcinoma (RCC) Submitted to the European Medicines Agency (EMA) by Eisai

HATFIELD, England, January 12, 2016 /PRNewswire/ --

FOR EMEA MEDIA ONLY: NOT FOR SWISS/AUSTRIAN/U.S. JOURNALISTS 

Lenvatinib, discovered and developed by Eisai, submitted for review for use in combination with everolimus to treat people with metastatic kidney cancer 

Eisai today submits a new Marketing Authorisation Application to the European Medicines Agency (EMA) for the use of lenvatinib in combination with everolimus, to treat people with unresectable advanced or metastatic renal cell carcinoma who have received one prior vascular endothelial growth factor (VEGF)-targeted therapy. Lenvatinib is an oral molecular tri-specific targeted therapy that has a potent selectivity. A similar application has already been submitted to the Food and Drug Administration in the U.S. Lenvatinib was granted an accelerated assessment in Europe by the EMA in October 2015.

The application is based on a phase II trial of lenvatinib, which when used in combination with everolimus showed progression-free survival was significantly extended in people with metastatic renal cell carcinoma (mRCC) versus everolimus alone. People treated with the combination regimen experienced a median progression-free survival of 14.6 months compared with 5.5 months for those who received everolimus alone (HR 0.40; 95% CI: 0.24-0.68; p<0.001). These data were presented at the American Society of Clinical Oncology (ASCO) in June 2015 and more recently published in Lancet Oncology.^[1]

"The phase II data showed that, for people with metastatic kidney cancer, the addition of lenvatinib offered a statistically significant progression free survival benefit compared to everolimus alone. The news that Eisai has submitted this application is hugely positive, for both clinicians and patients alike. The current outlook for people with this aggressive cancer is poor, and therefore the potential of lenvatinib is very exciting indeed," comments Dr Hilary Glen, Consultant Medical Oncologist, Beatson West of Scotland Cancer Centre, Scotland, UK.

Renal cell carcinoma is the most common form of kidney cancer. The standard treatment for unresectable advanced or metastatic 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.^[2]

"This submission is very important for clinicians, patients and Eisai. The development of lenvatinib was only possible with the support of so many pioneering scientists who have worked in this complex area of medicine for years. We are honored to submit this application and hope that patients in Europe will not have to wait long before accessing the treatment," comments Gary Hendler, President & CEO Eisai EMEA and President, Eisai Oncology Global Business Unit.

Lenvatinib has been approved for the treatment of refractory thyroid cancer in the United States, Europe Japan, Switzerland and South Korea and has been submitted for regulatory approval in 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.

Everolimus is a treatment recommended by the National Comprehensive Cancer Network guidelines as a 2nd-line therapy for unresectable advanced or metastatic renal cell carcinoma.

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 

Lenvatinib (E7080) 

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.^[3],[4] In addition, lenvatinib was found to have a new Type V binding mode of kinase inhibition that is distinct from existing compounds.^[5]

About Lenvatinib's Novel Binding Mode (Type V)^[5],[6]

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 Renal Cell Carcinoma 

RCC is a type of kidney cancer that 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.^[7]

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.^[8]

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.

References 

1. Motzer R, et al. Randomized phase 2 three-arm trial of lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma. The Lancet Oncology. 2015. Available at http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00290-9/abstract . Last accessed: December 2015

2. National Cancer Institute at the National Institute of Health. Available at: http://www.cancer.gov/types/kidney/patient/kidney-treatment-pdq . Last accessed: December 2015

3. Matsui J, et al. Multi-Kinase Inhibitor E7080 Suppresses Lymph Node and Lung Clin Cancer Res 2008;14:5459-65

4. 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;122:664-71

5. Okamoto K, et al. Distinct Binding Mode of Multikinase Inhibitor Lenvatinib Revealed by Biochemical Characterization. ACS Med. Chem. Lett 2015;6:89-94

6. Wu P. Small-molecule kinase inhibitors: an analysis of FDA-approved drugs. Drug Discovery Today, July 2015; 1-6

7. National Cancer Institue at the National Institute of Health. Available at:

http://www.cancer.gov/types/kidney/patient/kidney-treatment-pdq. Accessed: December 2015

8. Ljungberg et al. Guidelines on Renal Cell Carcinoma. Available at: http://uroweb.org/wp-content/uploads/10-Renal-Cell-Carcinoma_LR-LV2-2015.pdf . Last accessed December 2015