Eisai Announces Topline Results from Post-Marketing Study Supporting 24 mg as the Optimal Starting Dose of Lenvima (Lenvatinib) for Radioactive Iodine-Refractory Differentiated Thyroid Cancer

August 12, 2020 /BioonBIOON/ -- Eisai recently announced the top-line results from Study 211, a Phase II clinical trial evaluating Lenvima (Lenvima®, generic name: lenvatinib) for the treatment of radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC). Lenvima is an oral multi-receptor tyrosine kinase inhibitor. The study compared the efficacy and safety of two initial doses of Lenvima (18 mg vs. 24 mg, once daily). The results showed that, based on the objective response rate (ORR) at Week 24, the lower initial dose (18 mg) did not meet the non-inferiority criteria compared with the approved initial dose (24 mg) in patients with RAI-refractory DTC. These data support the selection of 24 mg as the appropriate initial dose for patients with RAI-refractory DTC.

Following the granting of priority review status and approval of Lenvima for the treatment of patients with locally recurrent or metastatic, progressive radioiodine-refractory differentiated thyroid cancer (DTC),Study 211, as a study for the U.S. Food and Drug Administration (FDA), a post-marketing commitment to the European Medicines Agency (EMA) and other regional regulatory authorities.

The primary objective of this randomized, double-blind, multicenter Phase II study was to determine whether a starting dose of Lenvima 18 mg once daily provides comparable efficacy (based on the objective response rate [ORR] at Week 24) and improved safety (based on the incidence of Grade ≥3 treatment-emergent adverse events [TEAEs]) compared with a starting dose of 24 mg once daily. Based on the ORR results at Week 24, the efficacy of the 18 mg dose group did not demonstrate non-inferiority to the 24 mg dose group. The primary safety endpoint indicated that the incidence of Grade 3 or higher TEAEs within the first 24 weeks of treatment was similar between the 24 mg and 18 mg dose groups.

Thyroid Cancer (Image source: lifebridgehealth.org)

EisaiTumorDr. Takashi Owa, Chief Drug Development and Chief Discovery Officer of the Business Group, stated, “These findings help enhance the efficacy and safety of Lenvima in patients with radioiodine-refractory differentiated thyroid cancer (RAI-r DTC), while providing an appropriate starting dose for these patients. Post-marketing studies such as this one exemplify Eisai’s continued commitment to prioritizing patient needs and safety through ongoing evaluation of our medicines. We thank the patients, their families, and clinical investigators for their participation in Study 211, and we look forward to presenting these results at upcoming medicalMeeting“Present the full results of this study above.”

Thyroid cancer is the most common endocrine malignancyTumor, global data indicate that its incidence is on the rise. It is estimated that there will be 52,890 new cases of thyroid cancer in the United States by 2020, with women being three times more likely to develop thyroid cancer than men. The most common types of thyroid cancer, papillary and follicular carcinomas (including Hürthle cell carcinoma), are classified as differentiated thyroid cancer (DTC) and account for approximately 90% of all cases. Although most patients with DTC can be cured through surgery and radioactive iodine (RAI) therapy, those with persistent or recurrent disease have a poorer prognosis.

Lenvima is a kinase inhibitor discovered and developed by Eisai. It is an oral multi-receptor tyrosine kinase (RTK) inhibitor that inhibits the kinase activities of vascular endothelial growth factor receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). In addition to inhibiting normal cellular functions, Lenvima also inhibits other kinases associated with pathological angiogenesis, tumor growth, and cancer progression, including fibroblast growth factor (FGF) receptors FGFR1–4, platelet-derived growth factor receptor alpha (PDGFRα), KIT, and RET. Lenvima can reduceTumorRelevant macrophages, increasing activated cytotoxic T cells.

As of now, the approved indications for Lenvima include: thyroid cancer, hepatocellular carcinoma (HCC), combination with everolimus for the treatment of renal cell carcinoma (second-line therapy), and combination with Keytruda (pembrolizumab, PD-1Tumorimmunotherapy) for the treatment of advanced endometrial cancer. In Europe, lenvatinib is marketed under the brand name Kisplyx for the treatment of renal cell carcinoma.

Eisai and Merck & Co. entered into a strategic collaboration in March 2018 to develop and commercialize Lenvima globally. In March and August 2018, Lenvima received approval in Japan, the United States, and the European Union, respectively, becoming the first new first-line treatment approved in these markets in the past decade for advanced or unresectable hepatocellular carcinoma (HCC).

Recently, the two parties submitted a new indication application for Lenvima in Japan for the treatment of unresectable thymic cancer. In June 2020, Lenvima was granted orphan drug designation in Japan for the treatment of unresectable thymic cancer.

In China, Lenvima (Lenvatinib) was approved in September 2018 as a monotherapy for the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC) who had not previously received systemic therapy. China is the world'sLiver Cancerthe country with the largest number of patients. In November 2018, Lenvima was launched in China, marking the first new systemic therapy for first-line treatment of unresectable hepatocellular carcinoma (HCC) in China in nearly a decade.

In December 2019, the new indication for Lenvima in the treatment of differentiated thyroid cancer (DTC) was approved, marking the second indication for this drug to be approved in China. (Bioon.com)

Original Source: Eisai Announces Topline Results from Study 211 Supporting 24 mg as theappropriate Starting Dose for LENVIMA (lenvatinib) in Patients with Differentiated Thyroid Cancer