Merck Announces Orphan Drug Designation for Investigational Therapy Tepotinib in Patients with NSCLC Harboring MET Gene Alterations

PR81776

DARMSTADT, Germany, Nov. 20, 2019 /PRNewswire=KYODO JBN/ --

- 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.

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Contact:

annemarie.eckhardt@merckgroup.com

Phone: +49-6151-72-26560

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