NRG fusion Market Insights

Key Highlights

• In 2027, the United States is expected to hold the largest share of the total NRG fusion market among the 7MM.
• Human neuregulins (NRGs) are small ligands belonging to the epidermal growth factor (EGF) family proteins. They are encoded by four different genes (NRG1-4) and are implicated in the activation of ErbB receptors to modulate both physiologic and neoplastic processes.
• 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, pancreatic cancers, and with a wide range of fusion partners.
• In December 2024, the US Food and Drug Administration (FDA) granted accelerated approval to BIZENGRI (zenocutuzumab-zbco) for the treatment of adults with advanced, unresectable, or metastatic non-small cell lung cancer (NSCLC) or pancreatic adenocarcinoma harboring neuregulin 1 (NRG1) gene fusions.
• In December 2024, Merus N.V. and Partner Therapeutics, entered into an agreement in which Merus has exclusively licensed to Partner Therapeutics the right to commercialize ZENO (zenocutuzumab) for the treatment of NRG1 fusion-positive (NRG1+) cancer in the United States.
• The emerging drug pipeline for NRG fusion is limited. Currently emerging drugs included are HMBD-001 (Hummingbird Bioscience), and others. 
• Key players in the NRG fusion market include, Merus, Hummingbird Bioscience, Salubris Biotherapeutics, Elevation Oncology, and several other companies. 

DelveInsight’s “Neuregulins (NRGs) Fusion – Market Size, Target Population, Competitive Landscape, and Market Forecast – 2034” report delivers an in-depth understanding of the NRG fusion, historical and competitive landscape as well as the NRG fusion market trends in the United States, EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan.

The NRG fusion market report provides current treatment practices, emerging drugs, market share of individual therapies, and current and forecasted 7MM NRG fusion market size from 2020 to 2034. The report also covers current NRG fusion treatment practices/algorithms and unmet medical needs to curate the best opportunities and assess the market’s potential.

Geography Covered

• The United States
• EU4 (Germany, France, Italy, and Spain) and the United Kingdom
• Japan

Study Period: 2020–2034

NRG Fusions Understanding and Treatment Algorithm

NRG Fusion Overview

Neuregulins (NRG) are a family of epidermal growth factor (EGF) ligands that are widely expressed in solid tumors. Four different genes named NRG-1, NRG-2, NRG-3, and NRG-4 code for more than 32 different NRG isoforms. The NRGs act by binding to the ErbB/HER family of receptor tyrosine kinases. Four different ErbB/HER receptors have been described in mammals: ErbB1/HER1/EGFR, ErbB2/HER2/neu, ErbB3/HER3, and ErbB4/HER4. ErbB/HER receptors and their ligands have been widely studied in cancer and linked to oncogenic transformation. They have also been the target for directed therapies, including monoclonal antibodies such as trastuzumab or pertuzumab against HER2, cetuximab against EGFR; or tyrosine kinase inhibitors such as lapatinib against EGFR and HER2.

NRG Fusion Treatment 

The first FDA-approved systemic therapy for NRG1 fusion-positive tumors is BIZENGRI  (zenocutuzumab-zbco). Standard therapy for advanced tumors harboring NRG 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. Development of new drugs for rare diseases is challenging, but the evaluation of drugs already approved for other indications is a pragmatic option. In the case of NRG1 fusion-driven tumors, existing ErbB-targeted treatments have potential as targeted therapies in tumors harboring NRG1 fusions. As NRG1 proteins are ligands of ErbB receptors, ErbB targeted treatments, such as monoclonal antibody BIZENGRI and small molecules such as GILOTRIF, are of particular interest.

Further details related to country-based variations are provided in the report

NRG Fusion Epidemiology

The NRG fusion epidemiology chapter in the report provides historical as well as forecasted epidemiology segmented as total incident cases of selected indication for NRG fusion, total eligible patient pool for NRG fusion in selected indication, total treated cases in selected indication for NRG fusion in the 7MM covering the United States, EU4 (Germany, France, Italy, and Spain), and the United Kingdom, and Japan from 2020 to 2034. 

• Among the 7MM, the US accounted for the highest incident cases of NRG Fusion in 2024.
• According to DelveInsight’s analysis, the total incident cases related to of NRG1-Fusion NSCLC were estimated to be ~840 in the US in 2024. 
• Among lung cancer cases, NSCLC accounts for approximately 85% of all diagnoses. This distribution highlights that NSCLC is the more prevalent form of lung cancer.
• Among EU4 and the UK, Germany accounted for the highest number of NRG Fusion Incident cases, while Spain accounted for the lowest number of cases.
• Among the stage-specific incident cases of NRG Fusion, metastatic cases contributed the most in the US.

NRG Fusion Drug Chapters

The drug chapter segment of the NRG fusion reports encloses a detailed analysis of NRG fusion late-stage and mid-stage pipeline drugs. It also helps understand the NRG 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.

NRG Fusion Marketed Drugs

BIZENGRI (Zenocutuzumab, MCLA-128): Merus

BIZENGRI (zenocutuzumab-zbco), developed by Merus, is a bispecific antibody that binds to the extracellular domains of HER2 and HER3 expressed on the surface of cells, including tumor cells, inhibiting HER2:HER3 dimerization and preventing NRG1 binding to HER3. BIZENGRI decreased cell proliferation and signaling through the phosphoinositide 3-kinase-AKT-mammalian target of rapamycin pathway. In addition, it mediates antibody-dependent cellular cytotoxicity. BIZENGRI showed antitumor activity in mouse models of NRG1+ lung and pancreatic cancers. 

In February 2025, New England Journal of Medicine (NEJM) published results of the registrational phase 2 eNRGy trial for BIZENGRI (zenocutuzumab), the first and only treatment indicated for adults with pancreatic adenocarcinoma or NSCLC that are advanced unresectable or metastatic and harbor a NRG1 gene fusion who have disease progression on or after prior systemic therapy.

NRG Fusion Emerging Drugs

HMBD-001: Hummingbird Bioscience

HMBD-001 represents a unique, highly-specific, anti-HER3 neutralizing antibody with a novel mechanism of action that offers significant potential for broad clinical benefit. Previous attempts to block the HER3 receptor, a key player in the signaling pathway that promotes cell division and tumor growth in cancer, have not proven to be efficacious. HER3 is activated by the binding of NRG1, which stabilizes a transient open conformation to allow it to form heterodimers with HER2/EGFR. In the presence of abundant HER2/EGFR, heterodimers can form without NRG1. Pre-clinical models have shown that HMBD-001 is able to effectively and uniquely bind to a difficult-to-target region on HER3, blocking the heterodimerization of HER3 with HER2/EGFR independent of NRG1 binding.

In May 2023, Hummingbird Bioscience entered into a clinical trial collaboration and supply agreement with Merck to evaluate HMBD-001 in combination with cetuximab in sqNSCLC.

Note: Detailed current therapies assessment will be provided in the full report of NRG fusion

NRG Fusion Market Outlook 

NRG fusions have been identified in over 10 solid tumor types, making it a strong candidate for a tumor-agnostic development approach. Moreover, an increase in awareness, research, and development can be seen in this area making it an attractive opportunity for the key players. Several ERBB3 inhibitors showing promising preclinical data are currently in different phases of clinical trials. Several of these are being tested in combination with ERBB2-targeting drugs in breast and gastric ERBB2-positive tumors.

In December 2024, Merus announced FDA Approval of BIZENGRI (zenocutuzumab-zbco) for NRG1+ pancreatic adenocarcinoma and NRG1+ NSCLC based on safety and efficacy data from the eNRGy study. NRG fusions are transforming oncogenic events that occur at a very low incidence across tumor types. These fusions can be seen in non–small cell lung cancer, breast cancer, colon cancer, pancreatic cancer, and cholangiocarcinoma—really, a multitude of tumor types. Drugs targeting the HER3 pathway, including monoclonal antibodies, bispecific [T-cell engagers], and antibody-drug conjugates; a whole multitude of strategies are being examined to target these fusions. Early data have demonstrated poor outcomes for patients with NRG1 fusions, and limited efficacy with available treatments represents a need for the development of novel therapeutic agents. Several key players, including Hummingbird Bioscience, Salubris Biotherapeutics, and others, are involved in developing drugs for NRG fusion for various indications. 

NRG Fusion Drugs Uptake

This section focuses on the uptake rate of potential approved and emerging NRG fusion expected to be launched in the market during 2020–2034.

NRG Fusion Pipeline Development Activities

The report provides insights into different therapeutic candidates in Phase III, Phase II, and Phase I. It also analyzes key players involved in developing targeted therapeutics. 

The presence of numerous drugs under different stages is expected to generate immense opportunity for NRG fusion market growth over the forecasted period.

NRG Fusion Pipeline development activities

The report covers information on collaborations, acquisitions and mergers, licensing, and patent details for NRG fusion emerging therapies. 

The increasing strategic collaborations among major market players to enhance the growth of their pipeline products are anticipated to drive market expansion. 

KOL Views

To keep up with current and future market trends, we take Industry Experts’ opinions working in the domain through primary research to fill the data gaps and validate our secondary research. Industry experts were contacted for insights on NRG fusion evolving treatment landscape, patient reliance on conventional therapies, patient therapy switching acceptability, drug uptake, along challenges related to accessibility.

DelveInsight’s analysts connected with 25+ KOLs to gather insights; however, interviews were conducted with 10+ KOLs in the 7MM. Centers such as Abramson Cancer Center, UC Davis Comprehensive Cancer Center, University of Texas MD Anderson Cancer Center, etc. were contacted. 

Their opinion helps understand and validate current and emerging therapy treatment patterns or NRG fusion market trends. This will support the clients in potential upcoming novel treatments by identifying the overall scenario of the market and the unmet needs.

Qualitative Analysis

We perform Qualitative and market Intelligence analysis using various approaches, such as SWOT analysis and Conjoint Analysis. In the SWOT analysis, strengths, weaknesses, opportunities, and threats in terms of gaps in disease diagnosis, patient awareness, physician acceptability, competitive landscape, cost-effectiveness, and geographical accessibility of therapies are provided. 

Conjoint Analysis analyzes multiple approved and emerging therapies based on relevant attributes such as safety, efficacy, frequency of administration, route of administration, and order of entry. Scoring is given based on these parameters to analyze the effectiveness of therapy.

In efficacy, the trial’s primary and secondary outcome measures are evaluated; for instance, in event-free survival, one of the most important primary outcome measures is event-free survival and overall survival. 

Further, the therapies’ safety is evaluated wherein the acceptability, tolerability, and adverse events are majorly observed, and it sets a clear understanding of the side effects posed by the drug in the trials. In addition, the scoring is also based on the probability of success, and the addressable patient pool for each therapy. According to these parameters, the final weightage score and the ranking of the emerging therapies are decided.

Market Access and Reimbursement

Reimbursement is a crucial factor that affects the drug’s access to the market. Often, the decision to reimburse comes down to the price of the drug relative to the benefit it produces in treated patients. To reduce the healthcare burden of these high-cost therapies, many payment models are being considered by payers and other industry insiders. The payment models are based on clinical outcomes, annuity payments, and expanded risk pools. The pharmaceutical companies must grant the following rebates: the general rebate of 7% of the manufacturer’s price will be paid by the pharmaceutical companies to the SHIs (Statutory health insurance funds) for all pharmaceuticals that are not subject to more specific price regulations. A special rebate of 10% of the manufacturer’s price is to be paid by the pharmaceutical companies to the SHIs for generics. Special rebates for vaccines are to be paid by the pharmaceutical companies to the SHIs and are calculated based on actual average prices in the four member states of the EU with gross national incomes. 

The report further provides detailed insights on the country-wise accessibility and reimbursement scenarios, cost-effectiveness scenario of approved therapies, programs making accessibility easier and out-of-pocket costs more affordable, insights on patients insured under federal or state government prescription drug programs, etc. 

Key Updates on NRG Fusion

• In December 2024, Merus announced FDA Approval of BIZENGRI (zenocutuzumab-zbco) for NRG1+ pancreatic adenocarcinoma and NRG1+ NSCLC based on safety and efficacy data from the eNRGy study.
• In September 2024, Hummingbird Biosciences presented the poster on “Phase Ib study to evaluate HMBD-001 in combination with docetaxel with or without cetuximab in participants with advanced squamous NSCLC, and HMBD-001 in combination with cetuximab in participants with advanced squamous cell cancers” at WCLC 2024.
• Elevation Oncology scientists presented in vitro and in vivo data of a seribantumab-based ADC for patients with HER3-expressing cancers at the AACR Annual Meeting 2024.

Scope of the Report

• The report covers a segment of key events, an executive summary, and a descriptive overview of NRG fusion, explaining its causes, diagnosis, and therapies (current and emerging).
• Comprehensive insight into the competitive Landscape, and forecasts, the future growth potential of treatment rate, drug uptake, and drug information have been provided.
• Additionally, an all-inclusive account of the current and emerging therapies and the elaborative profiles of late-stage and prominent therapies will impact the current landscape.
• A detailed review of the NRG fusion market, historical and forecasted market size, market share by therapies, detailed assumptions, and rationale behind our approach is included in the report, covering the 7MM drug outreach.
• The report provides an edge while developing business strategies, by understanding trends, through SWOT analysis expert insights/KOL views, and treatment preferences that help shape and drive the 7MM NRG fusion market.

NRG Fusion Report Insights

• NRG fusion Targeted Patient Pool
• Therapeutic Approaches
• NRG Fusion Pipeline Analysis
• NRG Fusion Market Size and Trends
• Existing and future Market Opportunity

NRG Fusion Report Key Strengths

• Ten years Forecast
• The 7MM Coverage 
• Key Cross Competition 
• Drugs Uptake and Key Market Forecast Assumptions

NRG Fusion Report Assessment

• Current Treatment Practices
• Unmet Needs
• Pipeline Product Profiles
• Market Attractiveness
• Qualitative Analysis (SWOT and Conjoint Analysis)

Key Questions

• What was the NRG fusion total market size, the market size by therapies, market share (%) distribution, and what would it look like in 2034? What are the contributing factors for this growth?
• Which drug is going to be the largest contributor in 2034?
• Which is the most lucrative market for NRG fusion?
• Which drug type segment accounts for maximum NRG fusion sales?
• What are the pricing variations among different geographies for approved therapies?
• How has the reimbursement landscape for NRG fusion evolved since the first one was approved? Do patients have any access issues that are driven by reimbursement decisions?
• What are the risks, burdens, and unmet needs of treatment for tumors harboring NRG fusion? What will be the growth opportunities across the 7MM for the patient population of NRG fusions?
• What are the key factors hampering the growth of the NRG fusion market?
• What key designations have been granted to the therapies for NRG fusion therapies?
• What is the cost burden of approved therapies on the patient?
• Patient acceptability in terms of preferred therapy options as per real-world scenarios?
• What are the country-specific accessibility issues of expensive, recently approved therapies? 

Reasons to buy

• The report will help develop business strategies by understanding the latest trends and changing dynamics driving the NRG fusion market.
• Understand the existing market opportunities in varying geographies and the growth potential over the coming years.
• Distribution of historical and current patient share based on real-world prescription data along with reported sales of approved products in the US, EU4 (Germany, France, Italy, and Spain) the United Kingdom, and Japan.
• Identifying strong upcoming players in the market will help devise strategies to help get ahead of competitors.
• Detailed analysis and ranking of indication-wise current and emerging therapies under the conjoint analysis section to provide visibility around leading indications.
• Highlights of Access and Reimbursement policies of approved therapies, barriers to accessibility of expensive off-label therapies, and patient assistance programs.
• To understand Key Opinion Leaders’ perspectives around the accessibility, acceptability, and compliance-related challenges of existing treatment to overcome barriers in the future.
• Detailed insights on the unmet needs of the existing market so that the upcoming players can strengthen their development and launch strategy.