Cellular-mesenchymal Epithelial Transition Factor (C-Met) Mutated Non-small Cell Lung Cancer (NSCLC) -Market Insights, Epidemiology and Market Forecast—2030

DelveInsight’s ‘Cellular-mesenchymal Epithelial Transition Factor (C-Met) Mutated Non-small Cell Lung Cancer (NSCLC) -Market Insights, Epidemiology and Market Forecast—2030’ report delivers an in-depth understanding of the c-Met Mutated NSCLC, historical and forecasted epidemiology as well as the c-Met Mutated NSCLC market trends in the United States, EU5 (Germany, France, Italy, Spain, and United Kingdom), and Japan.

The c-Met Mutated NSCLC market report provides current treatment practices, emerging drugs, c-Met Mutated NSCLC market share of the individual therapies, current and forecasted c-Met Mutated NSCLC market size from 2017 to 2030 segmented by seven major markets. The Report also covers current c-Met Mutated NSCLC treatment practice/algorithm, market drivers, market barriers and unmet medical needs to curate best of the opportunities and assesses underlying potential of the market.

Geography Covered
• The United States
• EU5 (Germany, France, Italy, Spain and the United Kingdom)
• Japan

Study Period: 2017–2030
C-Met Mutated NSCLC: Disease Understanding and Treatment Algorithm
C-Met Mutated NSCLC Overview

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer accounted for approximately 85% of all lung cancers. It can be defined as any type of epithelial lung cancer other than SCLC. It is mainly subcategorized into adenocarcinomas, squamous cell carcinomas, large cell carcinomas and several other types that occur less frequently include adenosquamous carcinomas, and sarcomatoid carcinomas. In these subtypes adenocarcinoma accounts for highest number of cases, i.e., approximately 47% followed by Squamous Cell Carcinoma and Large Cell Carcinoma.

There are several mutation associated with NSCLC but the most common are EGFR, KRAS, ROS-1 , BRAF , C-Met , PD-L1 expression and others. Among all the mutations C-Met accounted for approximately 4% of the total cases of NSCLC.

C-Met is a tyrosine kinase receptor, which is encoded in part by mesenchymal-epidermal transition (MET) exon 14. Mutations in the MET gene can cause increased c-MET signaling and oncogenic stimulation. Although c-MET mutation is rare, it is a targetable driver mutation.

C-Met Mutated NSCLC Diagnosis
For diagnosis of mutation associated with NSCLC a laboratory test is done to check for certain genes, proteins, or other molecules in a sample of tissue, blood, or other body fluid. Molecular tests check for certain gene or chromosome changes that occur in NSCLC. The guidelines do not recommend routine screening before treatment decision, there are drugs that can be used in patients who have c-MET mutation or amplification.

C-Met Mutated NSCLC Treatment
Currently there is no US FDA approved therapy is present for the treatment C-Met mutated NSCLC. However, several targeted therapies are used off-label such as crizotinib and others, but currently the mainstay of treatment is platinum based chemotherapy.

C-Met Mutated NSCLC Epidemiology
The C-Met mutated NSCLC epidemiology division provides the insights about historical and current c-Met Mutated NSCLC patient pool and forecasted trend for each seven major countries. It helps to recognize the causes of current and forecasted trends by exploring numerous studies and views of key opinion leaders. This part of the DelveInsight report also provides the diagnosed patient pool and their trends along with assumptions undertaken.

Key Findings
The total incident cases of C-Met mutated NSCLC in the 7MM were found to be 16,658 in 2017 which is expected to grow during the study period, i.e., 2017–2030.
The disease epidemiology covered in the report provides historical as well as forecasted C-Met mutated NSCLC epidemiology [segmented as Total Incident Cases of NSCLC, Total Incident Cases of NSCLC Patients by Histology, Total Diagnosed Cases of NSCLC Patients by Stages, Total NSCLC Cases of Patients by Genetic mutation/Biomarkers, and Treated Patient Pool of NSCLC] scenario of C-Met mutated NSCLC in the 7MM covering United States, EU5 countries (Germany, France, Italy, Spain, and United Kingdom), and Japan from 2017 to 2030.

Country Wise- c-Met Mutated NSCLC Epidemiology
Estimates shows that the highest incident population of C-Met mutated NSCLC is in the United States, followed by Germany, Japan, United Kingdom, and France in 2017.

C-Met Mutated NSCLC Drug Chapters
Drug chapter segment of the c-Met Mutated NSCLC report encloses the detailed analysis of c-Met Mutated NSCLC marketed drugs and late stage (Phase-III and Phase-II) pipeline drugs. It also helps to understand the c-Met Mutated NSCLC clinical trial details, expressive pharmacological action, agreements and collaborations, approval and patent details, advantages and disadvantages of each included drug and the latest news and press releases.

C-Met Mutated NSCLC Marketed Drugs
Tepmetko (tepotinib): Merck (only approved in Japan)

Tepmetko (tepotinib) is an oral MET inhibitor which is investigated by Merck KGaA, for the treatment of NSCLC. This product is designed to inhibit the oncogenic MET receptor signaling caused by MET (gene) alterations, including both METex14 skipping alterations and MET amplifications, or MET protein overexpression.

This investigational product was discovered in-house at Merck KGaA, Darmstadt, Germany, and it has been designed to have a highly selective mechanism of action, with the potential to improve outcomes in aggressive tumors that have a poor prognosis and harbor these specific alterations.

Tepotinib is currently under clinical investigation in NSCLC and not yet approved in any markets outside of Japan. The company is actively assessing the potential of investigating Tepotinib in combination with novel therapies and in other tumor indications. EMD Serono plans to file Tepotinib for regulatory review with the US FDA in 2020.

In March 2020, the Japanese Ministry of Health, Labour and Welfare (MHLW) has approved Tepmetko (Tepotinib) for the treatment of patients with unresectable, advanced or recurrent NSCLC with MET exon 14 (METex14) skipping alterations.

Products detail in the report…
C-Met Mutated NSCLC Emerging Drugs
Capmatinib (INC280): Novartis Pharmaceuticals

Novartis is investigating one of their lead compounds named, Capmatinib (INC280) in patients with NSCLC. It is an oral, potent and selective MET inhibitor. Currently this product is being investigated in multiple Phase II clinical trials. Capmatinib is licensed by Novartis from Incyte Corporation in 2009. Under the Collaboration and License Agreement, Novartis has exclusive worldwide development and commercialization rights to Capmatinib, and Incyte Corporation maintains certain rights to exercise options s for both co-development and co-detailing in the United States.

It is noteworthy to mention that INC280 has been granted with breakthrough designation for first-line treatment for patients with metastatic MET exon 14 skipping-mutated (METex14) NSCLC. This breakthrough therapy designation covers both treatment-naive patients and patients previously treated with platinum-based chemotherapy. It was also granted with Orphan Drug status by both the US FDA and Japan's Pharmaceuticals and Medical Devices Agency (PMDA).

In February 2020, the US FDA accepted and granted Priority Review to Capmatinib’s (INC280) NDA. Capmatinib is a MET inhibitor being evaluated as a treatment for first-line and previously treated patients with locally advanced or metastatic MET exon 14 skipping (METex14) mutated NSCLC.

Merestinib (LY2801653): Eli Lilly and Company
Merestinib (LY2801653) is an orally bioavailable, small molecule kinase inhibitor targeting several oncokinases. Merestinib selectively binds to c-Met, thereby inhibiting c-Met phosphorylation and disrupting c-Met signal transduction pathways. This may induce cell death in tumor cells overexpressing c-Met protein or expressing constitutively activated c-Met protein. c-Met, a receptor tyrosine kinase overexpressed or mutated in many tumor cell types, plays key roles in tumor cell proliferation, survival, invasion, metastasis, and tumor angiogenesis. Currently it is in phase II clinical trial for the patients with NSCLC Harboring MET Exon 14 Mutations as per evident by clinical trials.gov.
Products detail in the report…
C-Met Mutated NSCLC Market Outlook

C-Met is a plasma membrane tyrosine kinase activated by auto-phosphorylation after ligand binding. The c-MET was significantly associated with tumor growth in NSCLC. According to the data by literature it was suggested that MET amplification may play an important role in promoting drug resistance. So, the c-Met receptor is an attractive potential target for novel therapeutic inhibition in human cancers.

The current treatment paradigm of c-Met NSCLC is mainly dependent on the use of platinum based chemotherapy, off-label targeted therapies and PD-L1 inhibitors. In these three treatment approaches platinum based chemotherapy is the mainstay of treatment, currently.

Due to absence of US FDA approved therapies for the treatment of c-Met mutated NSCLC therapies like crizotinib is used off-label. It has already been granted with breakthrough therapy designation for the treatment of patients with metastatic NSCLC)with MET exon 14 alterations who progress after receiving platinum-based chemotherapy. Cabozantinib is another product which is used off-label in the treatment c-Met mutated NSCLC. It is a small molecule that inhibits the activity of tyrosine kinases including VEGF receptors, MET, AXL, and RET. These receptor tyrosine kinases are involved in both normal cellular function and in pathologic processes such as oncogenesis, metastasis, tumor angiogenesis, drug resistance and maintenance of the tumor microenvironment.

There is no US FDA approved product is present for the treatment of c-Met NSCLC but recently in March 2020, the Japanese Ministry of Health, Labour and Welfare (MHLW) has approved Tepmetko (tepotinib) for the treatment of patients with unresectable, advanced or recurrent NSCLC with MET exon 14 (METex14) skipping alterations. This therapy was also granted with Breakthrough Therapy Designation by the US FDA.

In conclusion, MET is an emerging molecular target for NSCLC. Several products designed to target MET have recently shown encouraging clinical results. However, deeper understanding of mechanisms of acquired resistance are necessary to develop strategies to overcome the inevitable arise of acquired resistance to targeted therapies.

Key Findings
According to DelveInsight c-Met Mutated NSCLC market in the 7MM is expected to change during the study period 2017–2030.The therapeutic market of c-Met Mutated NSCLC in seven major markets was found to be USD 186 million in 2017 which is expected to increase during study period (2017–2030).

The United States Market Outlook
In 2017, the total market size of c-Met Mutated NSCLC therapies was found to be USD 113 million in the United States which is expected to increase in the study period (2017–2030).

EU-5 Countries: Market Outlook
In 2017, the total market size of c-Met Mutated NSCLC therapies was found to be USD 60 million in the EU-5 countries which is expected to increase in the study period (2017–2030).

Japan Market Outlook
The total market size of c-Met Mutated NSCLC therapies in Japan was found to be USD 14 million in 2017.
C-Met Mutated NSCLC Pipeline Development Activities
The drugs which are in pipeline include:
1. Tepotinib (Merck): Phase II (US and EU), Approved (JP)
2. Capmatinib (INC280) (Novartis Pharmaceuticals): Pre-registration (Based on Phase II)
3. Merestinib (LY2801653) (Eli Lilly and Company): Phase II
4. TelisotuzumabVedotin (ABBV-399) (AbbVie): Phase II
Whole list of emerging products will be provided in the report...
Pipeline Development Activities
Key Points
1. In 2019, Novartis presented primary efficacy results from the GEOMETRY (Phase II) trial at ASCO for Capmatinib.
2. Janssen is enrolling patients into the Part 2 dose expansion cohorts, as the phase I study evaluates JNJ-6372 monotherapy activity in multiple NSCLC sub-populations with genomic alterations such as those with C797S resistance mutation or MET amplification.

C-Met Mutated NSCLC Drugs Uptake
Based, on the reported results of capmatinib and tepotinib, capmatinib has an edge over the tepotinib in first line but tepotinib has shown promising results in second line and above with better overall safety profile compared to capmatinib. On the other hand, due to limited visibility of results of other products these two therapies is expected to major share from the total market of C-Met Mutated NSCLC.

Access and Reimbursement Scenario in C-Met Mutated NSCLC Therapies
• The current scenario of therapeutics for NSCLC is mainly based on the use of targeted therapies and immunotherapy’s. Especially the current paradigm is mainly associated with treatment specific to mutations that occur in NSCLC.
• Due to the high costs, some of the therapies are not able to show their cost-effectiveness and are unable to get a recommendation by assessment agencies. So, the access and reimbursement scenario of drugs for NSCLC is not easy as cost-effectiveness is a major barrier for therapies in NSCLC.

KOL-Views
To keep up with current market trends, we take KOLs and SME’s opinion working in C-Met Mutated NSCLC domain through primary research to fill the data gaps and validate our secondary research. Their opinion helps to understand and validate current and emerging therapies treatment patterns or C-Met Mutated NSCLC market trend. This will support the clients in potential upcoming novel treatment by identifying the overall scenario of the market and the unmet needs.

Competitive Intelligence Analysis
We perform Competitive and Market Intelligence analysis of the c-Met Mutated NSCLC Market by using various Competitive Intelligence tools that includes – SWOT analysis, PESTLE analysis, Porter’s five forces, BCG Matrix, Market entry strategies etc. The inclusion of the analysis entirely depends upon the data availability.

Scope of the Report
• The report covers the descriptive overview of C-Met Mutated NSCLC, explaining its causes, signs and symptoms, pathophysiology and currently available therapies.
• Comprehensive insight has been provided into the C-Met Mutated NSCLC epidemiology and treatment in the 7MM.
• Additionally, an all-inclusive account of both the current and emerging therapies for C-Met Mutated NSCLC is provided, along with the assessment of new therapies, which will have an impact on the current treatment landscape.
• A detailed review of C-Met Mutated NSCLC market; historical and forecasted is included in the report, covering drug outreach in the 7MM.
• The report provides an edge while developing business strategies, by understanding trends shaping and driving the global C-Met Mutated NSCLC market.

Report Highlights
• In the coming years, C-Met Mutated NSCLC market is set to change due to the rising awareness of the disease and incremental healthcare spending across the world; which would expand the size of the market to enable the drug manufacturers to penetrate more into the market.
• The companies and academics are working to assess challenges and seek opportunities that could influence C-Met Mutated NSCLC R&D. The therapies under development are focused on novel approaches to treat/improve the disease condition.
• Major players are involved in developing therapies for C-Met Mutated NSCLC. Launch of emerging therapies, will significantly impact the C-Met Mutated NSCLC market.
• A better understanding of disease pathogenesis will also contribute to the development of novel therapeutics for C-Met Mutated NSCLC.
• Our in-depth analysis of the pipeline assets across different stages of development (Phase III and Phase II), different emerging trends and comparative analysis of pipeline products with detailed clinical profiles, key cross-competition, launch date along with product development activities will support the clients in the decision-making process regarding their therapeutic portfolio by identifying the overall scenario of the research and development activities.

C-Met Mutated NSCLC Report Insights
• Patient Population
• Therapeutic Approaches
• C-Met Mutated NSCLC Pipeline Analysis
• C-Met Mutated NSCLC Market Size and Trends
• Market Opportunities
• Impact of upcoming Therapies

C-Met Mutated NSCLC Report Key Strengths
• 11 Years Forecast
• 7MMCoverage
• C-Met Mutated NSCLC Epidemiology Segmentation
• Key Cross Competition
• Highly Analyzed Market
• Drugs Uptake

C-Met Mutated NSCLC Report Assessment
• SWOT Analysis
• Current Treatment Practices
• Unmet Needs
• Pipeline Product Profiles
• Conjoint Analysis
• Market Attractiveness
• Market Drivers and Barriers

Key Questions
Market Insights:
• What was the C-Met Mutated NSCLC Market share (%) distribution in 2017 and how it would look like in 2030?
• What would be the C-Met Mutated NSCLC total market Size as well as market size by therapies across the 7MM during the study period (2017–2030)?
• What are the key findings pertaining to the market across the 7MM and which country will have the largest C-Met Mutated NSCLC market size during the study period (2017–2030)?
• At what CAGR, the C-Met Mutated NSCLC market is expected to grow in 7MM during the study period (2017–2030)?
• What would be the C-Met Mutated NSCLC market outlook across the 7MM during the study period (2017–2030)?
• What would be the C-Met Mutated NSCLC market growth till 2030 and what will be the resultant market size in the year 2030?
• How would the market drivers, barriers and future opportunities affect the market dynamics and a subsequent analysis of the associated trends?
• C-Met Mutated NSCLC patient types/ pool where unmet need is more and whether emerging therapies will be able to address the residual unmet need?
• How emerging therapies are performing on the parameters like efficacy, safety, route of administration (RoA), treatment duration and frequencies on the basis of their clinical trial results?
• Among the emerging therapies, what are the potential therapies which are expected to disrupt the C-Met Mutated NSCLC market?

Epidemiology Insights:
• What is the disease risk, burden and unmet needs of the C-Met Mutated NSCLC?
• What is the historical C-Met Mutated NSCLC patient pool in seven major markets covering the United States, EU5 (Germany,France, Italy, Spain, and the United Kingdom) and Japan?
• What would be the forecasted patient pool of C-Met Mutated NSCLC in 7 major markets covering the United States, EU5 (Germany, France, Italy, Spain, and the United Kingdom) and Japan?
• What will be the growth opportunities in the 7MM with respect to the patient population pertaining to C-Met Mutated NSCLC?
• Out of all the 7MM countries, which country would have the highest incident population of C-Met Mutated NSCLC during the study period (2017–2030)?
• At what CAGR the population is expected to grow in the 7MM during the study period (2017–2030)?
• What are the various recent and upcoming events which are expected to improve the diagnosis of C-Met Mutated NSCLC?

Current Treatment Scenario, Marketed Drugs and Emerging Therapies:
• What are the current options for the treatment of C-Met Mutated NSCLC along with the approved therapy?
• What are the current treatment guidelines for the treatment of C-Met Mutated NSCLC in the US, Europe and Japan?
• What are the C-Met Mutated NSCLC marketed drugs and their MOA, regulatory milestones, product development activities, advantages, disadvantages, safety and efficacy, etc.?
• How many companies are developing therapies for the treatment of C-Met Mutated NSCLC?
• How many therapies are developed by each company for the treatment of C-Met Mutated NSCLC?
• How many emerging therapies are in mid stage, and late stage of development for the treatment of C-Met Mutated NSCLC?
• What are the key collaborations (Industry–Industry, Industry–Academia), Mergers and acquisitions, licensing activities related to the C-Met Mutated NSCLC therapies?
• What are the recent novel therapies, targets, mechanisms of action and technologies developed to overcome the limitation of existing therapies?
• What are the clinical studies going on for C-Met Mutated NSCLC and their status?
• What are the key designations that have been granted for the emerging therapies for C-Met Mutated NSCLC?
• What is the global historical and forecasted market of C-Met Mutated NSCLC?

Reasons to buy
The report will help in developing business strategies by understanding trends shaping and driving the C-Met Mutated NSCLC market.
To understand the future market competition in the C-Met Mutated NSCLC market and Insightful review of the key market drivers and barriers.
Organize sales and marketing efforts by identifying the best opportunities for C-Met Mutated NSCLC in the US, Europe (Germany, France, Italy, Spain, and the United Kingdom) and Japan.
Identification of strong upcoming players in market will help in devising strategies that will help in getting ahead of competitors.
Organize sales and marketing efforts by identifying the best opportunities for C-Met Mutated NSCLC market.
To understand the future market competition in the C-Met Mutated NSCLC market.