Eli Lilly Submits New Ramucirumab Indication for Marketing Approval in China

On August 23, the official website of the Center for Drug Evaluation (CDE) indicated that Eli Lilly and Company has submitted a marketing application for a new indication of ramucirumab (Acceptance No.: JXSS2101017). Ramucirumab (also known as 雷莫芦单抗) was first submitted by Eli Lilly for marketing approval in China in January this year (JXSS2100006).

Ramucirumab is a human IgG1 monoclonal antibody that specifically binds to vascular endothelial growth factor receptor 2 (VEGFR-2), inhibiting VEGFR-2 activation, thereby inhibiting ligand-induced endothelial cell proliferation and migration, and ultimately inhibiting tumor angiogenesis.

According to the Insight database, ramucirumab was first approved by the FDA on November 5, 2014, under the brand name CYRAMZA. It currently holds approval for five indications: gastric cancer, non-small cell lung cancer, colorectal cancer, hepatocellular carcinoma, and advanced/metastatic non-small cell lung cancer with EGFR mutations.

Ramucirumab FDA Approval History (Insight)

From the Insight Database (http://db.dxy.cn/v5/home/)

Since gaining market approval, its sales have continued to grow steadily. According to the Insight database, its sales revenue exceeded RMB 1 billion in 2020. Meanwhile, in the first half of 2021, Cyramza ranked ninth among Eli Lilly's products by sales, generating USD 509 million in revenue, a year-on-year increase of 3%.

Cyramza Historical Sales

From the Insight Database (http://db.dxy.cn/v5/home/)

In China, Eli Lilly submitted the clinical trial application for this product as early as 2010. According to the clinical trial registration information in the Insight database, a total of three clinical trials for ramucirumab have been registered in China, two of which are Phase III trials: (1) in combination with paclitaxel for advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma that is refractory to or has progressed after first-line therapy with platinum and fluoropyrimidine agents (CTR20160574); and (2) for advanced hepatocellular carcinoma in patients who were intolerant to or experienced disease progression following prior sorafenib treatment (CTR20170561). These two trials were completed on August 12, 2020, and March 15, 2021, respectively. Therefore, it is speculated that the indication submitted for marketing approval in January this year was second-line gastric cancer, while the indication submitted for approval this time is second-line hepatocellular carcinoma.

Ramucirumab Project Timeline

Status of Clinical Trials of Ramucirumab Initiated in China

From the Insight Database (http://db.dxy.cn/v5/home/)

However, although Eli Lilly's originator product has yet to be launched, Chinese biosimilar developers are already poised to enter the market. Currently, four ramucirumab biosimilars are under development by Qilu Pharmaceutical, Chia Tai Tianqing Pharmaceutical, Henlius, and Kelun-Biotech. Among them, Qilu Pharmaceutical has secured clinical trial approval but has not yet initiated the study, whereas the other three have already advanced to Phase I clinical trials.

Ramucirumab Biosimilar in China Entering Phase I Clinical Trials

From Insight Database (http://db.dxy.cn/v5/home/)