Eisai Co., Ltd., has submitted its application to the regulatory authority in South Korea (Ministry of Food and Drug Safety) for marketing approval of its novel in-house developed anticancer agent lenvatinib mesylate (lenvatinib) as a treatment for progressive radioiodine-refractory differentiated thyroid cancer.

Following the submission of marketing authorization applications in Japan, the United States and Europe, this marks the first time Eisai has submitted a marketing authorization application for lenvatinib in Asia.

Lenvatinib is an oral molecular targeted agent that selectively inhibits the activities of several different molecules including VEGFR, FGFR, RET, KIT and PDGFR, involved in angiogenesis and tumor proliferation. This potentially makes lenvatinib a first-in-class treatment in thyroid cancer, especially given that it simultaneously inhibits the activity of the three molecules VEGFR, FGFR and also RET via its novel binding mode.

The application submitted for South Korea was based on the positive results from a global phase III clinical study known as the SELECT (Study of (E7080) LEnvatinib in differentiated Cancer of the Thyroid) trial. (Please refer to the following notes for further details of the trial).An application seeking the approval of lenvatinib for the indication of thyroid cancer was submitted in Japan in June 2014 as the first in the world, followed by the submission of applications in both the United States and Europe in August 2014. Lenvatinib was granted Orphan Drug Designation for thyroid cancer in by the regulatory authorities in Japan, Europe and the United States. In addition, lenvatinib was also granted an accelerated assessment in Europe by the European Medicines Agency, and granted priority review status in the United States by the US Food and Drug Administration.

The number of patients newly diagnosed with thyroid cancer in 2012 in South Korea was estimated to be 33,000, and in Asia was estimated to be 144,000. Although treatment is possible for most types of thyroid cancer, there are few treatment options available once thyroid cancer has progressed, therefore it remains a disease with significant unmet medical needs.

Eisai is committed to exploring the potential clinical benefits of lenvatinib, and is working to obtain marketing approval in each country in Asia as soon as possible in order to further contribute to patients with thyroid cancer, and their families.

The SELECT (Study of (E7080) LEnvatinib in differentiated Cancer of the Thyroid) trial was a multicenter, randomized, double-blind, place bo-controlled phase III study of lenvatinib in patients with RR-DTC and radiographic evidence of disease progression within the prior 13 months (patients may have received=1 prior VEGFR-targeted therapies).

Patients were randomized 2:1 to either receive once-daily, oral lenvatinib (24 mg) or placebo therapy. The study enrolled 392 patients in over 100 sites in Europe, North and South America and Asia (including Japan) and was conducted by Eisai in collaboration with SFJ Pharma Ltd.

Compared to placebo, lenvatinib achieved a statistically significant improvement (Hazard Ratio (HR) 0.21; 99% CI: 0.14-0.31; p<0.0001) in progression free survival (PFS), which was the primary objective of the study. The median PFS with lenvatinib and placebo was 18.3 months and 3.6 months respectively. Secondary endpoints included overall response rate, overall survival (OS) and safety. The results for overall response rate were 64.8% in the lenvatinib group and 1.5% in the placebo group. Complete response was observed in 1.5% (4 patients) of the lenvatinib group and zero in the placebo group. The median time to response for lenvatinib was 2.0 months. Median OS has not been reached yet in both groups. The most common lenvatinib treatment-related adverse events (TRAEs) (events with an incidence rate of at least 40%) were hypertension (67.8%), diarrhea (59.4%), decreased appetite(50.2%), weight loss (46.4%) and nausea (41.0%). The most common TRAEs (events with an incidence rate of at least 5%) of Grade 3 or higher (Common Terminology Criteria for Adverse Events) in cluded hypertension (41.8%), proteinuria (10.0%), weight loss (9.6%), diarrhea (8.0%), and decreased appetite (5.4%).

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.