Merck KGaA Submits NDA for c-Met Inhibitor Tepotinib in China

On March 30, the CDE website showed that Merck KGaA's c-Met inhibitor tepotinib was submitted for marketing authorization in China.

The receptor tyrosine kinase MET gene, fully named Mesenchymal Epithelial Transition Factor (MET), also known as cellular Mesenchymal Epithelial Transition Factor (c-Met) or Hepatocyte Growth Factor Receptor (HGFR). Skipping mutations in exon 14 of the MET gene (MET ex14) account for 3% to 4% of NSCLC cases. Patients with this aggressive form of lung cancer are typically elderly and have a poor prognosis. There is an urgent clinical need for targeted therapies that can produce durable anti-tumor activity to improve the lives of patients with this challenging disease.

Tepotinib, independently developed by Merck KGaA of Germany, can inhibit the oncogenic MET receptor signaling caused by MET gene mutations. The drug was first approved for marketing in Japan in March 2020, making it the world’s first orally administered c-Met inhibitor to gain regulatory approval for the treatment of advanced non-small cell lung cancer (NSCLC) with MET gene mutations.

In February 2021, tepotinib received accelerated FDA approval via priority review for the treatment of adult patients with metastatic NSCLC harboring MET exon 14 skipping mutations, regardless of whether these patients had previously received treatment. Tepotinib is the first and only once-daily oral c-Met inhibitor approved by the FDA.

A key Phase II VISION study evaluated the efficacy and safety of tepotinib monotherapy in patients with MET exon 14 skipping mutation advanced NSCLC. The study results showed that the ORR for tepotinib was 43% in both treatment-naïve and previously treated patients. The mDOR was 10.8 months for treatment-naïve patients and 11.1 months for previously treated patients. Sixty-seven percent of treatment-naïve patients and 75% of previously treated patients achieved durable responses lasting more than 6 months; 30% of treatment-naïve patients and 50% of previously treated patients achieved durable responses lasting more than 9 months.

The first c-Met inhibitor approved for marketing in China is Savolitinib developed by Hutchmed. It was granted conditional approval by the National Medical Products Administration in June 2021 for the treatment of adult patients with locally advanced or metastatic NSCLC who have MET exon 14 skipping mutations and whose disease has progressed after platinum-based chemotherapy or who are intolerant to standard platinum-based chemotherapy.

In addition, Haihe Pharmaceutical's c-Met inhibitor Glumetinib was submitted for marketing approval on February 25 this year and has been included in the priority review, with an expected approval within the year.