Eisai's Lenvatinib Nears Approval for Second Indication in China: Differentiated Thyroid Cancer

Recently, the marketing application for the second indication of Eisai’s lenvatinib (Acceptance Numbers: JXHS1900157, JXHS1900158) has been updated to “Under Review,” with approval expected in the near future for the treatment of differentiated thyroid cancer.

Lenvatinib was approved for marketing in China in September 2018 for first-line treatment of liver cancer. Within less than two years of its launch, sales revenue grew from RMB 199 million in 2018 to RMB 853 million, representing an annual growth rate of 328.64%.

(Source: CDE)

In January 2016, the NMPA approved lenvatinib to conduct a multicenter, randomized, double-blind, placebo-controlled Phase III clinical trial in China for the treatment of radioactive I-131-refractory differentiated thyroid cancer.

(Source: Drug Clinical Trial Registration and Information Publicity Platform)

In December 2019, the New Drug Application (NDA) for the second indication of lenvatinib (Acceptance Numbers: JXHS1900157, JXHS1900158), namely differentiated thyroid cancer, was submitted based on clinical trial data from the SELECT study. The median progression-free survival (mPFS) in the lenvatinib group was 18.3 months, compared with 3.6 months in the placebo group (Hazard Ratio 0.21 [99% CI: 0.14–0.31]; p<0.001).

The first indication is liver cancer.

Lenvatinib Mesylate Capsules (Lenvatinib, Code: E7080, Brand Name: Lenvima) are a multi-target, oral tyrosine kinase (RTKs) inhibitor targeting vascular endothelial growth factor receptors (VEGFR) 1-3, fibroblast growth factor receptors (FGFR) 1-4, RET, KIT, and platelet-derived growth factor receptor β (PDGFRβ).

In September 2018, the National Medical Products Administration (NMPA) approved lenvatinib monotherapy for the treatment of patients with unresectable hepatocellular carcinoma (HCC) who had not previously received systemic therapy. The approved specification was 4 mg, making lenvatinib the second first-line therapeutic agent for HCC after sorafenib. Currently, in China, the price of lenvatinib is RMB 16,800 per box, with each box containing 30 capsules of 4 mg each. For HCC patients weighing less than 60 kg, the recommended dosage is 8 mg/day (2 capsules); for those weighing 60 kg or more, the recommended dosage is 12 mg/day (3 capsules). Unfortunately, lenvatinib was excluded from the national reimbursement drug list during the medical insurance negotiations in November 2019 and is currently not covered by medical insurance.

(Compiled from public sources)

According to Eisai’s annual report, in 2019, the sales revenue of lenvatinib reached RMB 7.038 billion, representing a year-on-year increase of 78.75% (in addition to sales revenue, there were also milestone payments and one-time option-related payments from Merck & Co.). The sales revenue in China was RMB 853 million.

Chia Tai Tianqing Becomes First to File for Production of Generic Lenvatinib

Lenvatinib: Eisai’s relevant patents include the general formula of the compound, preparation methods, intermediates, crystal forms, indications, formulations, and combination therapies. The compound patent expired in China on October 19, 2021. The preparation method patent expired in China on November 8, 2024. The crystal form patent expired in China on December 22, 2024.

Currently, a total of six pharmaceutical companies have submitted marketing applications for Class 4 generic lenvatinib. Among them, in June 2019, Chia Tai Tianqing submitted a marketing application for lenvatinib under the new Class 4 category, becoming the first company to file for production of a generic version.

(Source: CDE)

Significantly Prolong Overall Survival (OS) in Chinese Patients with Hepatocellular Carcinoma

Lenvatinib Significantly Improves Overall Survival (OS) in Chinese Patients with Hepatocellular Carcinoma.

At the CSCO conference in September 2017, clinical data on lenvatinib for Chinese liver cancer patients were announced. The median overall survival (OS) in the lenvatinib group was as high as 15.0 months, compared to only 10.2 months in the sorafenib group, representing a substantial increase of 4.8 months.

(Data source: The Lancet)

The primary reason for the aforementioned differences in efficacy lies in the particularly prominent effectiveness of lenvatinib in treating hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC), given that over 90% of HCC cases in China are caused by HBV infection. It can be said that lenvatinib is a targeted therapy tailor-made for Chinese patients with HCC.

China is a country with a high burden of liver cancer, with 466,000 new cases diagnosed annually. Of these, 80% are patients with intermediate- to advanced-stage disease, and there are 422,000 deaths each year. Consequently, the market prospects for lenvatinib are substantial, and its future sales are expected to continue rising.

Furthermore, the combination of lenvatinib and PD-1 inhibitors has demonstrated remarkable efficacy. For more detailed information, please refer to “Lenvatinib, a Blockbuster Drug for Liver Cancer, Submits Marketing Application to CDE for Its Second Indication》。

Author Biography:Caicai, Master of Pharmacy from Shanghai Jiao Tong University, formerly worked at the Institute of Scientific and Technical Information, and is currently a professional in the drug regulatory system, specializing in interpreting industry regulations and pharmaceutical research trends.

Original Title:In 2019, Lenvatinib Generated RMB 850 Million in Sales in China! The Second Indication Is Set for Imminent Approval