Rare NRG1 Fusion - Market Insight, Epidemiology and Market Forecast - 2032

This ‘Rare NRG1 Fusion - Market Insights, Epidemiology, and Market Forecast - 2032' report delivers an in-depth understanding of the Rare NRG1 Fusion, historical and forecasted epidemiology as well as the Rare NRG1 Fusion market trends in the United States, the EU-5 (Germany, France, Italy, Spain, and the United Kingdom) and Japan.

The Rare NRG1 Fusion market report provides current treatment practices, emerging drugs, Rare NRG1 Fusion market share of the individual therapies, current and forecasted Rare NRG1 Fusion market size from 2019 to 2032 segmented by seven major markets. The Report also covers the current Rare NRG1 Fusion treatment practice/algorithm, and unmet medical needs to curate the best of the opportunities and assesses the underlying potential of the market.

Geography Covered

• The United States
• EU-5 (Germany, France, Italy, Spain, and the United Kingdom)
• Japan

Study Period: 2019-2032

Rare NRG1 Fusion: Disease Understanding and Treatment Algorithm

Rare NRG1 Fusion Overview

NRG1 (Neuregulin 1) gene fusions are potentially actionable oncogenic drivers that are present in some solid tumors. NRG1 fusions result in ErbB-mediated pathway activation and present a rational therapeutic target. Oncogenic fusions of NRG1 may cause excess accumulation of the NRG1-fusion protein at the cell surface. This causes persistent activation of ErbB receptor tyrosine kinases that drive excess activity in the mTOR and MAPK pathways and promote tumorigenesis. The NRG1 gene encodes ligands for the ERBB2 (HER2)-ERBB3 heterodimeric receptor tyrosine kinase. Gene fusions of NRG1 such as CD74-NRG1 and SLC33A2-NRG1 have been found at low frequency in a wide range of carcinomas including lung, breast, colorectal, ovarian, and pancreatic cancers and with a wide range of fusion partners.

CD74-NRG1 fusion gene has been identified in a portion of invasive mucinous adenocarcinomas (IMA) of the lung. However, the function of the CD74-NRG1 fusion gene in adenocarcinoma pathogenesis and the mechanisms by which it may impart protumorigenic characteristics to cancer stem cells (CSC) is still unclear. A range of NRG1 fusion partners beyond CD74 has been identified, and they also vary among cancer types. In NSCLC, other fusion partners include the SDC4, SLC3A2, and ATP1B1 genes. In other malignancies, the genes SETD4, TSHZ2, and ZMYM2 (ovarian cancer); ADAM9 and COX10-AS1 genes (breast cancer); and CDH1 and VTCN1 genes (pancreatic cancer) are among known fusion partners of NRG1.

Rare NRG1 Fusion Diagnosis

Fusions involving the neuregulin-1 gene (NRG1) were first identified by transcriptome sequencing of lung adenocarcinomas, which revealed fusion of CD74 to NRG1. NRG1-fusion proteins and genes in solid tumors are detected primarily using immunohistochemistry and fluorescence in situ hybridization (FISH) techniques, DNA next-generation sequencing (NGS), and targeted gene fusion panels on RNA. The gold standard for the detection of NRG1 gene fusions is RNA sequencing in comparison with DNA sequencing. Although fluorescence in situ hybridization (FISH) can be used as a pre-screening method for its detection, only genetic sequencing will allow the identification of the gene fusion. RNA-sequencing is associated with higher sensitivity for genetic rearrangements and can increase the detection of NRG1 gene fusions compared with DNA-based methods, which often do not cover the large introns in NRG1.

Rare NRG1 Fusion Treatment

NRG1 gene fusions result in the activation of ErbB2-/ErbB3-mediated signaling pathways and may function as oncogenic drivers. NRG1 fusions have emerged as a potential therapeutic target across multiple tumor types, including NSCLC.

For NRG1 fusions, there are currently no approved targeted therapies. Standard therapy for advanced tumors harboring NRG1 fusions remains chemotherapy and/or immunotherapy or novel anti-PD-1 or anti-PD-L1 agents. The problem with utilizing these therapies is that response tends to be suboptimal for patients with NRG1 fusions. Several clinical reports have demonstrated that NRG1 fusions are a viable, actionable target in tumors, with responses seen on inhibition of ERBB family members.

Rare NRG1 Fusion Epidemiology

The Rare NRG1 Fusion epidemiology division provides insights about the historical and current Rare NRG1 Fusion patient pool and forecasted trends for 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 report also provides the diagnosed patient pool and their trends along with assumptions undertaken.

Key Findings

In the year 2021, the total incident case of Rare NRG1 Fusion were 5,733 cases in the 7MM which are expected to grow during the study period, i.e., 2019-2032.

The disease epidemiology covered in the report provides historical as well as forecasted Rare NRG1 Fusion epidemiology [segmented as Total Incident Cases of NRG1 Fusion in selected solid tumors, Total Stage-specific Cases of NRG1 Fusion, and Total Treated cases of NRG1 Fusion] in the 7MM covering the United States, EU-5 countries (Germany, France, Italy, Spain, and the United Kingdom) and Japan from 2019 to 2032.

Country Wise- Rare NRG1 Fusion Epidemiology

• Estimates show that the highest cases of NRG1 Fusion in the 7MM were in the United States, followed by Japan, Germany, France, Italy, the United Kingdom, and Spain in 2021.
• The incident cases include the following cancers; cholangiocarcinoma, pancreatic cancer, renal cell carcinoma, ovarian cancer, NSCLC, breast cancer, bladder cancer, and colorectal cancer.
• In the United States, the total number of incident cases of NRG1 Fusion were 2,122 cases in the year 2021 which are expected to grow during the study period, i.e., 2019-2032.
• In the year 2021, the total incident cases of NRG1 Fusion in EU-5 were highest in Germany which are expected to grow during the study period, i.e., 2019-2032.
• In Japan, the total number of incident cases of NRG1 Fusion was 1,201 cases in the year 2021 which are expected to grow during the study period, i.e., 2019-2032.
• In the US, NSCLC and Breast cancer has the highest number of the NRG1 fusion cases.
• In the US, the total NRG1 fusions metastatic cases (including locally advanced) was 1,076 in the year 2021 which are expected to grow during the study period, i.e., 2019-2032.

Rare NRG1 Fusion Drug Chapters

The drug chapter segment of the Rare NRG1 Fusion report encloses the detailed analysis of Rare NRG1 Fusion late stage (Phase-III and Phase-II) pipeline drugs. It also helps to understand the Rare NRG1 Fusion 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.

Rare NRG1 Fusion Emerging Drugs

MM-121/Seribantumab (Elevation Oncology)

MM-121 (Seribantumab) is a fully human monoclonal antibody by Elevation Oncology. It is designed to stop the HER3 signaling that sustains an NRG1 fusion-positive tumor. Seribantumab binds to HER3 so that the NRG1 fusion protein that over-activates it, cannot bind to it. Seribantumab is being developed as a precise treatment path for patients whose tumor growth is driven by an NRG1 fusion. MM-121 is currently in the Phase II clinical development stage. It is now being studied in patients with solid tumors of any origin that test positive for an NRG1 fusion. US FDA granted seribantumab Fast Track designation and Orphan Drug Designation for development in patients with heregulin-positive, locally advanced or metastatic non-small cell lung cancer (NSCLC) whose disease has progressed following immunotherapy.

Zenocutuzumab/MCLA-128 (Merus)

Zenocutuzumab (MCLA-128) is an experimental medicine that is being developed by Merus. It is believed to work by blocking the action of the growth factor NRG1, a protein that can be overproduced due to NRG1 Fusions and prohibiting it from binding to HER3. HER3 is a protein that sits on the surface of cancer cells, which when it combines with a second surface protein HER2, sends signals to drive tumor growth and survival. NRG1 induces the combination of HER2 and HER3. Zenocutuzumab is a bispecific antibody, which means it can recognize two different proteins, specifically HER2 and HER3. It is designed to have a dock and block mechanism. Currently, Zenocutuzumab is in the Phase II clinical development stage for the treatment of NRG1 fusion Solid Tumors.

HMBD-001 (Hummingbird Bioscience)

HMBD-001 is a unique antibody engineered to bind strongly and specifically to the dimerization interface of HER3, thereby interfering with HER3's ability to dimerize and fully blocking its activation, regardless of NRG1 binding. This gives HMBD-001 a novel action mechanism for inhibiting tumor growth and drug resistance in HER3-driven cancers. Preclinical models have shown that HMBD-001 potently inhibits the activation of the MAPK/PI3K signaling pathway - and consequently prevents tumor growth and drug resistance. Currently it is being investigated in Phase I for NRG fusion protein.

Note: Detailed emerging therapies assessment will be provided in the final report.

Rare NRG1 Fusion Market Outlook

NRG1 Fusion is a rare but potentially actionable oncogenic driver that is present in some solid tumors. These fusions can promote pathologic signaling via MAPK and other canonical pathways. The most frequently reported NRG1 fusion is CD74-NRG1, which most commonly occurs in patients with invasive mucinous adenocarcinomas (IMAs) of the lung, although several other NRG1 fusion partners have been identified in patients with lung cancer, including ATP1B1, SDC4, and RBPMS. While there are studies of therapeutic efficacy with agents that target Erb-B2/Erb-B3, little is known about the characteristics of these fusions. Being a rare disorder, there is no specific treatment for NRG1 Fusion.

Currently, there are no approved targeted therapies for NRG1 fusions. Standard therapy for advanced tumors harboring NRG1 fusions remains chemotherapy and/or immunotherapy or novel anti-PD-1 or anti-PD-L1 agents. The problem with utilizing these therapies is that response tends to be suboptimal for patients with NRG1 fusions. The outcomes of preclinical studies have suggested that repurposing FDA-approved HER inhibitors, such as Afatinib (Gilotrif), may have a highly attractive therapeutic strategy for NRG1 fusion-positive tumors.

At present, some companies have indulged themselves in initiating clinical trials that investigate new treatment options or studying how to use existing treatment options better. Key players such as Elevation Oncology (Seribantumab), Merus (Zenocutuzumab), Hummingbird Bioscience (HMBD-001), and several others are investigating their candidates for the management of Rare NRG1 Fusions.

Key Findings

The Rare NRG1 Fusion market size in the 7MM is expected to change during the study period 2019-2032. The therapeutic market of Rare NRG1 Fusion in the seven major markets is expected to increase during the study period (2019-2032) with a CAGR of 25.9%. According to the estimates, the highest market size of NRG1 Fusion is found in the United States followed by Japan.

The United States Market Outlook

The total market size of NRG1 Fusion therapies in the United States is expected to increase with a CAGR of 26.8% in the study period (2019-2032).

EU-5 Countries: Market Outlook

The total market size of NRG1 Fusion therapies in Germany in EU-5 countries is expected to increase with a CAGR of 24.1% in the study period (2019-2032).

Japan Market Outlook

The total market size of NRG1 Fusion therapies in Japan is expected to increase with a CAGR of 26.1% in the study period (2019-2032).

Rare NRG1 Fusion Pipeline Development Activities

The drugs which are in forecast include:
1. MM-121/Seribantumab (Elevation Oncology)
2. Zenocutuzumab/MCLA-128 (Merus)
3. HMBD-001 (Hummingbird Bioscience)
The report provides insights into different therapeutic candidates in Phase II, Phase III and Phase I stage. It also analyzes key players involved in developing targeted therapeutics.

Pipeline Development Activities

The report covers the detailed information of collaborations, acquisition and merger, licensing and patent details for Rare NRG1 fusion emerging therapies.

Note: Detailed emerging therapies assessment will be provided in the final report.

Analyst Commentary

• According to the estimates, the highest market size in rare NRG1 Fusions will be contributed from the United States owing to the higher patient pool and higher treatment cost followed by Japan.
• Due to the relative novelty of mutation and lack of extensive research and development, the pipeline of rare NRG1 fusions is still evolving and most of the drugs are still in the very early phase of development.
• Among emerging therapies, Zenocutuzumab from Merus is expected to garner the highest patient share owing to novel MoA, visibility around the efficacy data from the ongoing trials, and also the early mover advantage.

NRG1 fusion Drugs Uptake

• This section focuses on the rate of uptake of the potential drugs expected to get launched in the market during the study period 2019-2032. The analysis covers Rare NRG1 fusion market uptake by drugs; patient uptake by therapies; and sales of each drug. For example- Seribantumab which is an intravenous infusion monoclonal HER3 inhibitor/ERBB-3 receptor antagonist binds to HER3, so the NRG1 fusion protein that over-activates it cannot bind to it. Currently, the drug is in the Phase II stage of clinical development for NRG1 fusion positive locally advanced or metastatic solid tumors. Elevation Oncology believes that the design and conduct of CRESTONE, subject to discussions with the FDA, may support the submission of a BLA for accelerated approval in advanced solid tumors harboring an NRG1 fusion. The drug is expected to launch in US in 2024. As per our analysis, Seribantumab drug uptake in the US is expected to be medium- fast with an estimated peak share of 30%.

KOL-Views

To keep up with current market trends, we take KOLs and SME's opinion working in the Rare NRG1 Fusion 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 Rare NRG1 Fusion market trends. 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

The publisher performs Competitive and Market Intelligence analysis of the Rare NRG1 Fusion 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 Rare NRG1 Fusion, explaining its causes, signs and symptoms, pathophysiology, and currently available therapies.
• Comprehensive insight has been provided into the Rare NRG1 Fusion epidemiology and treatment in the 7MM.
• Additionally, an all-inclusive account of both the current and emerging therapies for Rare NRG1 Fusion is provided, along with the assessment of new therapies, which will have an impact on the current treatment landscape.
• A detailed review of the Rare NRG1 Fusion 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 Rare NRG1 Fusion market.

Report Highlights

• In the coming years, the Rare NRG1 Fusion 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 Rare NRG1 Fusion 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 Rare NRG1 Fusion. The launch of emerging therapies will significantly impact the Rare NRG1 Fusion market.
• A better understanding of disease pathogenesis will also contribute to the development of novel therapeutics for Rare NRG1 Fusion.
• 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.

Rare NRG1 Fusion Report Insights

• Patient Population
• Therapeutic Approaches
• NRG1 Fusion Pipeline Analysis
• NRG1 Fusion Market Size and Trends
• Market Opportunities
• Impact of upcoming Therapies

Rare NRG1 Fusion Report Key Strengths

• 11 Years Forecast
• 7MM Coverage
• NRG1 Fusion Epidemiology Segmentation
• Key Cross Competition
• Highly Analyzed Market
• Drugs Uptake

Rare NRG1 Fusion Report Assessment

• SWOT Analysis
• Current Treatment Practices
• Unmet Needs
• Pipeline Product Profiles
• Biomarker Testing
• Market Attractiveness

Key Questions Answered

Market Insights:

• What was the Rare NRG1 Fusion Market share (%) distribution in 2019 and how it would look like in 2032?
• What would be the Rare NRG1 Fusion total market size as well as market size by therapies across the 7MM during the study period (2019-2032)?
• What are the key findings of the market across the 7MM and which country will have the largest Rare NRG1 Fusion market size during the study period (2019-2032)?
• At what CAGR, the Rare NRG1 Fusion market is expected to grow in the 7MM during the study period (2019-2032)?
• What would be the Rare NRG1 Fusion market outlook across the 7MM during the study period (2019-2032)?
• What would be the Rare NRG1 Fusion market growth till 2032 and what will be the resultant market size in the year 2032?
• How would the market drivers, barriers, and future opportunities affect the market dynamics and subsequent analysis of the associated trends?
• Rare NRG1 Fusion 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 based on their clinical trial results?
• Among the emerging therapies, what are the potential therapies which are expected to disrupt the Rare NRG1 Fusion market?

Epidemiology Insights:

• What are the disease risks, burdens, and unmet needs of the Rare NRG1 Fusion?
• What is the historical Rare NRG1 Fusion patient pool in the 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 Rare NRG1 Fusion in the 7 major markets covering the United States, the EU5 (Germany, France, Italy, Spain, and the United Kingdom) and Japan?
• What will be the growth opportunities in the 7MM concerning the patient population about Rare NRG1 Fusion?
• Out of all the 7MM countries, which country would have the highest incident population of Rare NRG1 Fusion during the study period (2019-2032)?
• At what CAGR the population is expected to grow in the 7MM during the study period (2019-2032)?
• What are the various recent and upcoming events which are expected to improve the diagnosis of Rare NRG1 Fusion?

Current Treatment Scenario and Emerging Therapies:

• What are the current options for the treatment of Rare NRG1 Fusion?
• What are the current treatment guidelines for the treatment of Rare NRG1 Fusion in the US, Europe and Japan?
• How many companies are developing therapies for the treatment of Rare NRG1 Fusion?
• How many therapies are developed by each company for the treatment of Rare NRG1 Fusion?
• How many emerging therapies are in the mid-stage and late stages of development for the treatment of Rare NRG1 Fusion?
• What are the key collaborations (Industry-Industry, Industry-Academic), Mergers and acquisitions, licensing activities related to the Rare NRG1 Fusion 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 Rare NRG1 Fusion and their status?
• What are the key designations that have been granted for the emerging therapies for Rare NRG1 Fusion?
• What is the global historical and forecasted market of Rare NRG1 Fusion?

Reasons to Buy

• The report will help in developing business strategies by understanding trends shaping and driving the Rare NRG1 Fusion market.
• To understand the future market competition in the Rare NRG1 Fusion market and Insightful review of the key market drivers and barriers.
• Organize sales and marketing efforts by identifying the best opportunities for Rare NRG1 Fusion in the US, Europe (Germany, France, Italy, Spain, and the United Kingdom) and Japan.
• Identification of strong upcoming players in the 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 the Rare NRG1 Fusion market.
• To understand the future market competition in the Rare NRG1 Fusion market.