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Tepmetko (tepotinib) Receives Positive CHMP Opinion for Advanced NSCLC with METex14 Skipping Alterations

Dec 20, 2021 01:15 CST Updated 01:15
Merck Group

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Committee for Medicinal Products for Human Use

Committee for Medicinal Products for Human Use (CHMP)The Committee for Medicinal Products for Human Use (CHMP) is the committee within the European Medicines Agency (EMA) responsible for human medicines. The CHMP replaced the former Committee for Proprietary Medicinal Products (CPMP) in May 2004.The CHMP plays a vital role in the authorization of medicines in the European Union (EU). In the centralized procedure, the CHMP is responsible for: 1) conducting initial assessments of marketing authorization applications across the EU; assessing modifications or extensions to existing marketing authorizations (“variations”); considering recommendations from the Agency’s Pharmacovigilance Risk Assessment Committee regarding the safety of medicines on the market, and, where necessary, advising the European Commission to amend the marketing authorization of a medicinal product, or to suspend or withdraw it from the market.The CHMP also evaluates medicines authorized at the national level that are referred to the EMA, with the aim of maintaining a harmonized position throughout the EU.Furthermore, the CHMP and its working groups promote the development of medicines and pharmaceutical regulation by: providing scientific advice to companies researching and developing new medicines; developing scientific and regulatory guidelines to assist pharmaceutical companies in preparing marketing authorization applications for human medicines; and collaborating with international partners to harmonize regulatory requirements.


News on December 19, 2021 /BioValleyBIOON/ -- Merck KGaA recently announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion, recommending the approval of the targeted anticancer drug Tepmetko (tepotinib): a highly selective, once-daily oral MET inhibitor, as a monotherapy.For the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) who have previously received immunotherapy and/or platinum-based chemotherapy, require systemic therapy, and harbor MET exon 14 skipping alterations (METex14 skipping).Now, the CHMP opinion will be submitted to the European Commission (EC) for review, which is expected to make a final review decision in the first quarter of 2022.

It is estimated that lung cancer is the second most common cancer in Europe and the leading cause of cancer-related deaths, resulting in 388,000 deaths in 2018. Alterations in the MET signaling pathway, including METex14 skipping changes, are found in 3%-4% of NSCLC cases, which are associated with advanced disease and poor prognosis.

Tepmetko is the world's first approved oral MET inhibitor for the treatment of patients with advanced NSCLC carrying MET gene alterations.Tepmetko was approved in Japan in March 2020 and in the United States in February 2021 for the treatment of NSCLC patients with METex14 skipping alterations. In Japan, Tepmetko has been granted Orphan Drug Designation (ODD) and SAKIGAKE Designation (innovative medicine). In the United States, Tepmetko has been granted Orphan Drug Designation (ODD) and Breakthrough Therapy Designation (BTD).

Tepmetko is also available in the United States.FDAThe first once-daily oral MET inhibitor approved for the treatment of patients with metastatic NSCLC harboring METex14 skipping alterations. September 2020,NovartisTargeted anticancer drug Tabrecta (capmatinib) approvedFDAThe first approved MET inhibitor for the treatment of adult patients with metastatic NSCLC carrying METex14 skipping alterations.

Tepmetko and Tabrecta are both approved for: patients who have not previously received treatment (first-line) and patients who have previously received treatment (treated). In terms of administration, Tepmetko is taken orally once daily, while Tabrecta is taken orally twice daily.

The positive review opinion of the CHMP is based on data from the pivotal Phase 2 VISION study (NCT02864992). This is the largest clinical study conducted to date in patients with metastatic NSCLC carrying METex14 skipping alterations, in which a total of 275 patients with METex skipping alterations NSCLC (median age: 72.6 years) received Tepmetko treatment.

Preliminary analysis data were previously published in the international top medical journal, The New England Journal of Medicine (NEJM): As of January 1, 2020, a total of 152 patients had received Tepmetko treatment, and 99 patients had undergone at least 9 months of follow-up.In the pooled biopsy group, the objective response rate (ORR) by independent review was 46%, and the median duration of response (DOR) was 11.1 months.. The ORR was 48% in the 66 patients of the liquid biopsy group and 50% in the 60 patients of the tissue biopsy group. Positive results were obtained in 27 patients using both methods. In addition,Tepmetko Demonstrates Consistent and Durable Responses in Both Treatment-Naïve Patients (First-Line Group) and Previously Treated Patients (Second-Line Group).

Tepotinib Molecular Structure (Source: chemicalbook.com)

Globally, lung cancer is the most common type of cancer and the leading cause of cancer-related deaths, with 2 million new cases diagnosed and 1.7 million deaths annually. Currently, three types of MET signaling pathway alterations (including METex14 skipping mutations, MET amplification, and MET protein overexpression) have been identified across various types of cancers, which are associated with...TumorThe invasive behavior and poor clinical prognosis are related. It is estimated that MET signaling pathway alterations occur in 3-5% of NSCLC cases.

Tepotinib is an orally administered MET kinase inhibitor discovered internally by Merck. It potently and highly selectively inhibits oncogenic signaling driven by MET (gene) alterations—including METex14 skipping mutations, MET amplification, and MET protein overexpression—with the potential to improve treatment outcomes for patients with aggressive tumors carrying these specific MET alterations.Besides NSCLC, Merck is also actively evaluating tepotinib in combination with new therapies for otherTumorIndications.

September 2019, United StatesFDATepotinib Granted Breakthrough Therapy Designation (BTD) for the Treatment of Metastatic NSCLC Patients with METex14 Skipping Alterations Who Have Progressed Following Platinum-Based Chemotherapy.

Currently, Merck is also conducting another study, INSIGHT 2 (NCT03940703), to evaluate the combination of tepotinib and the tyrosine kinase inhibitor (TKI) osimertinib for EGFR-mutated, MET-amplified, locally advanced or metastatic NSCLC patients with acquired resistance to prior EGFR TKI therapy. (Bioon.com)