FDA Approves Anticancer Agent Lenvima as Treatment for Radioactive Iodine-Refractory Dirrerentiated Thyroid Cancer

Eisai Co. Ltd has announced that its US subsidiary Eisai Inc. has received approval of its in-house developed novel anticancer agent Lenvima (lenvatinib mesylate) as a treatment for locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (RAI-R DTC) from FDA. Lenvima was granted priority review status by the FDA, and was ultimately approved 6 months from the submission of the New Drug Application in August 2014, 2 months ahead of the FDA priority review action date. This marks the first country in the world where the agent has received marketing authorization.

Lenvima is an orally administered molecular targeted agent that selectively inhibits the activities of several different molecules including VEGFR, FGFR, RET, KIT and PDGFR. In particular, the agent simultaneously inhibits VEGFR, FGFR and also RET which are especially involved in tumor angiogenesis and proliferation of thyroid cancer. Furthermore, Lenvima has been confirmed through X-ray crystal structural analysis to be the first compound to demonstrate a new binding mode (Type V) to VEGFR2, and exhibits rapid and potent inhibition of kinase activity, according to kinetic analysis.

The approval was based on the results of a multicenter, randomized, double-blind, placebo-controlled Phase III study (the SELECT study) of 392 patients with progressive RAI-R DTC. In the study's primary endpoint of progression-free survival (PFS), Lenvima demonstrated a statistically significant extension in PFS compared to placebo (p<0.001; median PFS in the Lenvima group: 18.3 months, median PFS in the placebo group: 3.6 months; Hazard Ratio (HR) 0.21 [99% CI: 0.14-0.31]). In addition, Lenvima demonstrated a statistically significant improvement in response rate (sum of complete and partial responses) compared to placebo (p<0.001; Lenvima: 64.8% vs placebo: 1.5%). In particular, complete response was observed in 1.5% (4 patients) of the Lenvima group and zero in the placebo group. The most common Lenvima treatment-related adverse events of any grade, which occurred in more than 40% of patients in the Lenvima group, were hypertension (67.8%), diarrhea (59.4%), fatigue or asthenia (59.0%), decreased appetite (50.2%), weight loss (46.4%) and nausea (41.0%).

Currently, the agent is undergoing regulatory review in Japan and the EU, as well as Switzerland, South Korea, Canada, Singapore, Russia, Australia and Brazil, and Lenvima was also granted accelerated assessment in the EU. Eisai will continue to file applications seeking regulatory approval for the agent in countries around the world, and the company will market the agent in those countries where approval has been received. Furthermore, Eisai is conducting a global Phase III trial of Lenvima in hepatocellular carcinoma as well as Phase II studies of Lenvima in several other tumor types such as renal cell carcinoma and non-small cell lung cancer.