- Japanese Ministry of Health, Labour and Welfare grants orphan drug designation for diseases that affect fewer than 50,000 patients in Japan, and for which significant unmet medical need exists - MET exon 14 (METex14) skipping alterations and MET amplifications are present in 3-5% of non-small cell lung cancer patients and correlate with poor prognosis - In March 2018, tepotinib received SAKIGAKE 'fast-track' regulatory designation in Japan and in September 2019 received Breakthrough Therapy Designation in the US Merck, a leading science and technology company, today announced that the Japanese Ministry of Health, Labour and Welfare (MHLW) has granted orphan drug designation (ODD) for its investigational therapy tepotinib* for patients with non-small cell lung cancer (NSCLC) harboring MET gene alterations. "Advanced NSCLC harboring MET gene alterations is associated with aggressive tumor behavior and poor clinical prognosis," said Luciano Rossetti, Global Head of Research & Development for the Biopharma business of Merck. "This orphan drug designation helps to advance this program within Japan and, coupled with the SAKIGAKE 'fast-track' designation received last year, provides important mechanisms, such as priority review, to quickly deliver this medicine to Japanese patients with this difficult-to-treat disease." The Japan MHLW ODD program is designed to promote research and development of orphan drugs for diseases that affect fewer than 50,000 patients in Japan, and for which significant unmet medical need exists. An investigational drug can qualify for ODD if there is no approved alternative treatment option or if there is an expectation of high efficacy or safety compared to existing treatment options. Drugs receiving ODD qualify for several benefits intended to support development, such as guidance and subsidies for research and development activities from the MHLW, preferential tax treatment, priority consultation for clinical development, and priority review of applications. Discovered in-house at Merck, tepotinib is an investigational oral MET inhibitor that is designed to inhibit the oncogenic MET receptor signaling caused by MET (gene) alterations, including both MET exon 14 skipping alterations and MET amplifications, or MET protein overexpression. It has been designed to have a highly selective mechanism of action,1 with the potential to improve outcomes in aggressive tumors that have a poor prognosis and harbor these specific alterations. Alterations of the MET signaling pathway are found in various cancer types, including 3-5% of NSCLC cases, and correlate with aggressive tumor behavior and poor clinical prognosis.2-4 Lung cancer is the most common type of cancer worldwide, with two million cases diagnosed annually.5 Tepotinib is being investigated in the ongoing VISION study (NCT02864992), which showed preliminary efficacy in patients harboring METex14 skipping alterations detected by liquid biopsy (LBx) or tissue biopsy (TBx) across different lines of treatment. Results from the interim analysis of the VISION study were presented in an oral presentation at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting6 and the 2019 Japan Society of Medical Oncology (JSMO) Annual Meeting.7 The use of both LBx and TBx to identify patients for the VISION study is intended to support improved patient selection and is consistent with the company's focus on patient-centric drug development. Tepotinib is also being investigated in the INSIGHT 2 study (NCT03940703) in combination with the tyrosine kinase inhibitor (TKI) osimertinib in epidermal growth factor receptor (EGFR) mutated, MET amplified, locally advanced or metastatic NSCLC having acquired resistance to prior EGFR TKI. In March 2018, the Japan MHLW granted SAKIGAKE 'fast-track' designation for tepotinib in advanced (stage IIIB/IV) NSCLC harboring METex14 skipping alterations and, in September 2019, the US Food and Drug Administration (FDA) granted Breakthrough Therapy Designation (BTD) for tepotinib in patients with metastatic NSCLC harboring METex14 skipping alterations who progressed following platinum-based cancer therapy. *Tepotinib is currently under clinical investigation and not approved for any use anywhere in the world. About Non-Small Cell Lung Cancer With two million cases diagnosed annually, lung cancer (including trachea, bronchus and lung) is the most common type of cancer worldwide, and the leading cause of cancer-related death, with 1.7 million mortality cases worldwide.5 Alterations of the MET signaling pathway, including MET exon 14 skipping alterations and MET amplifications, occur in 3-5% of NSCLC cases.2-4 About Tepotinib Tepotinib, discovered in-house at Merck, is an investigational oral MET inhibitor that is designed to inhibit the oncogenic MET receptor signaling caused by MET (gene) alterations, including both MET exon 14 skipping alterations and MET amplifications, or MET protein overexpression. It has been designed to have a highly selective mechanism of action,1 with the potential to improve outcomes in aggressive tumors that have a poor prognosis and harbor these specific alterations. Tepotinib is currently being investigated in NSCLC and Merck, is actively assessing the potential of investigating tepotinib in combination with novel therapies and in other tumor indications. References 1)Bladt, F, et al. Clin Cancer Res 2013;19:2941-2951 2)Reungwetwattana T, et al. Lung Cancer 2017;103:27-37. 3)Mo HN, et al. Chronic Dis Transl Med 2017; 3(3):148-153. 4)Lutterbach B, et al. Cancer Res 2007;67:2081–8. 5)Bray F, et al. CA Cancer J Clin. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. 2018;68(6):394–424. https://doi.org/10.3322/caac.21492 PMID:30207593 6)Paik P, et al. J Clin Oncol 2019;37: (suppl; abstr 9005). 7)Sakai H, et al. Ann Oncol 2019;30(Suppl_6):Abstract MO2-15-5. All Merck Press Releases are distributed by e-mail at the same time they become available on the Merck Website. Please go to www.merckgroup.com/subscribe to register online, change your selection or discontinue this service. 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