Phase III Select Trial of Lenvatinib Meets Primary Endpoint of Improved Progression Free Survival in the Treatment of Radioiodine-Refractory Differentiated Thyroid Cancer

HATFIELD, England, February 3, 2014 /PRNewswire/ --



Eisai announced today that the Phase III SELECT trial (Study 303) of lenvatinib, an investigational selective tyrosine kinase inhibitor (TKI) with a novel binding mode,^[1] met its primary endpoint. Compared to placebo, lenvatinib showed a highly statistically significant improvement in progression free survival (PFS) in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC). The preliminary safety analyses showed that the five most common adverse reactions were hypertension, diarrhoea, decreased appetite, decreased weight and nausea.

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 12 months, treated with once-daily, oral lenvatinib (24mg) 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.

Based on these clinical results, Eisai will submit marketing authorisation applications for lenvatinib to health authorities in the U.S., Japan and Europe.

"These results show the potential role of the investigational drug lenvatinib in this rare, hard-to-treat cancer," said Kenichi Nomoto, PhD, President, Oncology Product Creation Unit, Eisai Product Creation Systems. "RR-DTC remains an unmet need with a limited number of treatment options."

Thyroid cancer is the most common endocrine malignancy and global figures show that its incidence has increased significantly over the last 50 years.^[2] In Europe alone, almost 63,000 cases of thyroid cancer were diagnosed in 2012.^[3] Differentiated thyroid cancer accounts for approximately 90% of all thyroid cancers.^[4] For the majority of patients prognosis is good with a survival rate of 85% at ten years.^[5] For those patients whose cancer is refractory to radioiodine treatment, prognosis is poor with a ten-year survival rate of 15%.^[4]

Lenvatinib, discovered and developed by Eisai, was granted orphan drug designation (ODD) for the treatment of follicular and papillary thyroid cancer by the European Commission in April 2013. This followed ODD in the U.S. for follicular, medullary, anaplastic and metastatic or locally advanced papillary thyroid cancer and Japan (thyroid cancer).

Eisai has also initiated a global Phase III trial of lenvatinib in hepatocellular carcinoma (HCC) and is conducting Phase II studies of lenvatinib in several other tumour types. Eisai is committed to understanding the potential clinical benefits of lenvatinib in order to further contribute to patients with cancer, including patients with RR-DTC, and their families.

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 well being 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 (E7080)

Lenvatinib is an orally active, selective inhibitor of receptor tyrosine kinases (RTKs), including KDR (VEGFR-2), Flt-1 (VEGFR-1), FGFR1, PDGFR-β and c-kit involved in angiogenesis and tumour proliferation.^[6],[7] It is currently under investigation as a treatment for thyroid, hepatocellular, endometrial and other solid tumour types. Eisai has initiated a global Phase III trial with lenvatinib in hepatocellular carcinoma (HCC) and is conducting Phase II studies of lenvatinib in several other tumour types.

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.^[8] It is more common in women than in men and most are in their 40s or 50s at time of diagnosis.^[2]

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.^[9] The remaining cases are classified as either medullary (5-7% of cases) or anaplastic (1-2% of cases).^[10]While most DTC patients are curable with surgery and radioactive iodine treatment, the prognosis for those patients who do respond is poor. ^[5] There are limited treatment options for this difficult-to-treat, life-threatening and treatment-refractory form of thyroid cancer.^[11]

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

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 loss
• 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 include Europe, the Middle East, Africa, Russia and Oceania (EMEA). Eisai EMEA has sales and marketing operations in over 20 markets, including the United Kingdom, France, Germany, Italy, Spain, Switzerland, Sweden, Ireland, Austria, Denmark, Finland, Norway, Portugal, Czech Republic, Slovakia, the Netherlands, Belgium, Luxembourg, Russia and the Middle East.

For further information please visit our web site http://www.eisai.co.uk

About the SFJ Pharmaceuticals Group

The SFJ Pharmaceuticals Group, which includes SFJ Pharma Ltd., is a Global Drug Development Company, which provides a unique co-development partnering model for some of the world's top Pharmaceutical and Biotechnology companies. SFJ uses its financial strength and core team of pharmaceutical development experts to provide highly customised partnering models in which SFJ provides the funding and clinical development supervision, necessary to obtain regulatory approval for some of the most promising drug development programmes of Pharmaceutical and Biotechnology companies.

References

1. Data on file, Eisai.Co.Ltd

2. Brito J et al. Thyroid cancer: zealous imaging has increased detection and treatment of low risk tumours. BMJ 2013; 347

3. Thyroid Cancer. International Agency for Research on Cancer. http://eco.iarc.fr/eucan/Cancer.aspx?Cancer=35 (last accessed: October 2013)

4. Deshpande H, et al. Axitinib: The evidence of its potential in the treatment of advanced thyroid cancer. Core Evidence 2009; 4: 43-48

5. Gild M et al. Multikinase inhibitors: a new option for the treatment of thyroid cancer. Nature Reviews Endocrinology. 2011; 7: 617-624

6. Matsui J, Funahashi Y, Uenaka T et al. Multi-kinase inhibitor E7080 suppresses lymph node and lung metastases of human mammary breast tumour MDA-MB-231 via inhibition of vascular endothelial growth factor-receptor (VEGF-R) 2 and VEGF-R3 kinase. Clin Cancer Res 2008; 14: 5459-65

7. Matsui J, Yamamoto Y, Funahashi Y, et al. E7080, a novel inhibitor that targets multiple kinases, has potent anti-tumour activities against stem cell factor producing human small cell lung cancer H146, based on angiogenesis inhibition. Int J Cancer 2008; 122: 664-71

8. National Cancer Institute at the National Institute of Health http://www.cancer.gov/cancertopics/pdq/treatment/thyroid/Patient/page1/AllPages#1 [http://www.cancer.gov/cancertopics/pdq/treatment/thyroid/Patient/page1/AllPages ] (last accessed: January 2014)

9. Cooper DS et al. Thyroid. 2009;19(11):1167-1214

10. Thyroid Cancer Basics. 2011. http://www.thyca.org

11. Bible K, Suman V, Molina J et al. Efficacy of pazopanib in progressive, radioiodine-refractory metastatic differentiated thyroid cancers: results of a phase 2 consortium study. Lancet Oncology 2010; 11(10): 962-972

Job code: lenvatinib-UK0019 Date of preparation: February 2014