FDA Approval of Tepotinib Sets Stage for Merck Versus Novartis Showdown in Metastatic NSCLC Space

Following the approval of Japan’s Ministry of Health, Labour and Welfare (MHLW) in March 2020, Merck’s oral MET inhibitor, TEPMETKO (tepotinib), has now bagged a regulatory win in the US. On February 3rd, the USFDA granted accelerated approval for the drug to treat adult patients with metastatic NSCLC harboring the MET exon 14 (METex14) skipping alteration.

Lung cancer is the second most common type of cancer and the leading cause of cancer-related deaths globally. Non-small cell lung cancer (NSCLC) is the most prevalent, with around 2 million cases diagnosed each year. Among them, approximately 3% to 5% develop mutations in the mesenchymal-epithelial transition (MET) signaling pathway, including METex14 skipping alterations and MET amplifications. Such mutations are associated with aggressive tumor behavior and poor clinical prognosis.

With this approval, TEPMETKO has become the first and only once-daily oral MET inhibitor for this disease indication. The drug will be administered orally as two 225 mg tablets (450 mg).

“This approval of TEPMETKO by the FDA is an important milestone on our mission to significantly improve the treatment of cancer where MET plays a driving role,” said Danny Bar-Zohar, M.D., Global Head of Development for the Healthcare business of Merck KGaA, Darmstadt, Germany. “Our focus now is to ensure TEPMETKO is accessible to patients in the United States and fully integrated into clinical practice given the important advance it represents for indicated patients as an oral once-a-day precision medicine.”

Positive Trial Data

The FDA approval is a result of encouraging data observed in the ongoing VISION (NCT02864992) trial that evaluated tepotinib as a monotherapy in 152 patients suffering from NSCLC with METex14 skipping alterations. Patients in the Phase II trial were given 450 mg of TEPMETKO once daily until disease progression or unacceptable toxicity.

The primary and additional endpoints of the study were the overall response rate (ORR) and the median duration of response (DOR), respectively. Results showed that TEPMETKO demonstrated an ORR of 43% and a DOR of 10.8 months in the 69 patients who received the treatment for the first time. In the 83 previously treated patients, those stats were 43% and 11.1 months.

Some common adverse reactions include edema, fatigue, nausea, and diarrhea, to name a few. Besides, the drug can also cause interstitial lung disease, hepatotoxicity, and embryo-fetal toxicity.

Market Competition

TEPMETKO will go head to head with Novartis’ kinase inhibitor TABRECTA (capmatinib), which received FDA approval last May on the back of impressive data in the GEOMETRY [NCT02414139] study. However, with once-daily dosing of 450 mg, TEPMETKO might hold the edge over TABRECTA, whose recommended dosage is 400 mg orally twice daily.

Besides, three other MET-targeting TKIs, namely crizotinib (Pfizer), cabozantinib (Exelixis Inc.), and glesatinib (Mirati Therapeutics), are currently under trials for this indication. Crizotinib has already bagged FDA’s Breakthrough Therapy Designation and is already approved to treat ROS-1 Positive NSCLC.

Data from the PROFILE 1001 [NCT00585195] trial show that crizotinib registered an ORR of 32% with a median PFS of 7.3 months and median DOR of 9.1 months in NSCLC patients harboring METex14 alterations. Merck and Novartis could expect a third player in the market sooner or later if things fall in place for crizotinib.

Related Article: FDA Greenlights Pfizer’s Xalkori for a Rare Form of Non-Hodgkin Lymphoma

References

1. https://www.prnewswire.com/news-releases/fda-approves-tepmetko-as-the-first-and-only-once-daily-oral-met-inhibitor-for-patients-with-metastatic-nsclc-with-metex14-skipping-alterations-301221542.html
2. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-tepotinib-metastatic-non-small-cell-lung-cancer
3. https://www.nature.com/articles/s41591-019-0716-8

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Author

Rajaneesh K. Gopinath