entrectinib - Profile

What are the generic sources for entrectinib and what is the scope of freedom to operate?

Entrectinib is the generic ingredient in one branded drug marketed by Genentech Inc and is included in two NDAs. There are fourteen patents protecting this compound. Additional information is available in the individual branded drug profile pages.

Summary for entrectinib

International Patents:	130
US Patents:	14
Tradenames:	1
Applicants:	1
NDAs:	2
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for entrectinib

DrugPatentWatch^® Estimated Loss of Exclusivity (LOE) Date for entrectinib

Constraining patent/regulatory exclusivity:

11,253,515

Dosage:

CAPSULE;ORAL

Constraining patent/regulatory exclusivity:

TREATMENT OF PEDIATRIC PATIENTS OLDER THAN 1 MONTH UP TO 12 YEARS OF AGE WITH SOLID TUMORS THAT HAVE A NEUROTROPHIC TYROSINE RECEPTOR KINASE (NTRK) GENE FUSION, AS DETECTED BY AN FDA-APPROVED TEST WITHOUT A KNOWN ACQUIRED RESISTANCE MUTATION, ARE METASTATIC OR WHERE SURGICAL RESECTION IS LIKELY TO RESULT IN SEVERE MORBIDITY, AND HAVE PROGRESSED FOLLOWING TREATMENT OR HAVE NO SATISFACTORY ALTERNATIVE THERAPY

Dosage:

PELLETS;ORAL

^*The generic entry opportunity date is the latter of the last compound-claiming patent and the last regulatory exclusivity protection. Many factors can influence early or later generic entry. This date is provided as a rough estimate of generic entry potential and should not be used as an independent source.

US Patents and Regulatory Information for entrectinib

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Genentech Inc	ROZLYTREK	entrectinib	CAPSULE;ORAL	212725-001	Aug 15, 2019		RX	Yes	No	9,616,059
Genentech Inc	ROZLYTREK	entrectinib	CAPSULE;ORAL	212725-001	Aug 15, 2019		RX	Yes	No	10,231,965
Genentech Inc	ROZLYTREK	entrectinib	CAPSULE;ORAL	212725-001	Aug 15, 2019		RX	Yes	No	9,649,306
Genentech Inc	ROZLYTREK	entrectinib	CAPSULE;ORAL	212725-001	Aug 15, 2019		RX	Yes	No	8,673,893
Genentech Inc	ROZLYTREK	entrectinib	CAPSULE;ORAL	212725-001	Aug 15, 2019		RX	Yes	No	9,255,087
Genentech Inc	ROZLYTREK	entrectinib	CAPSULE;ORAL	212725-001	Aug 15, 2019		RX	Yes	No	10,561,651
Genentech Inc	ROZLYTREK	entrectinib	CAPSULE;ORAL	212725-001	Aug 15, 2019		RX	Yes	No	10,738,037		Y	Y

EU/EMA Drug Approvals for entrectinib

Company	Drugname	Inn	Product Number / Indication	Status	Generic	Biosimilar	Orphan	Marketing Authorisation	Marketing Refusal
Roche Registration GmbH	Rozlytrek	entrectinib	EMEA/H/C/004936Rozlytrek as monotherapy is indicated for the treatment of adult and paediatric patients 12 years of age and older with solid tumours expressing a neurotrophic tyrosine receptor kinase (NTRK) gene fusion,who have a disease that is locally advanced, metastatic or where surgical resection is likely to result in severe morbidity, andwho have not received a prior NTRK inhibitorwho have no satisfactory treatment options.Rozlytrek as monotherapy is indicated for the treatment of adult patients with ROS1 positive, advanced non small cell lung cancer (NSCLC) not previously treated with ROS1 inhibitors.	Authorised	no	no	no	2020-07-31

International Patents for entrectinib

Country	Patent Number	Title	Estimated Expiration
Australia	2015220832
Brazil	112016015818
Canada	2933623
Chile	2016001507
China	106029073
Eurasian Patent Organization	033457
Eurasian Patent Organization	201691151

Supplementary Protection Certificates for entrectinib

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
3107541	21/2021	Austria		PRODUCT NAME: ENTRECTINIB ODER EIN PHARMAZEUTISCH ANNEHMBARES SALZ DAVON; REGISTRATION NO/DATE: EU/1/20/1460 (MITTEILUNG) 20200803
2176231	CR 2020 00058	Denmark		PRODUCT NAME: ENTRECTINIB ELLER ISOMERER, TAUTOMERER ELLER FARMACEUTISK ACCEPTABLE SALTE DERAF; REG. NO/DATE: EU/1/20/1460 20200803
2176231	46/2020	Austria		PRODUCT NAME: ENTRECTINIB ODER ISOMERE, TAUTOMERE ODER PHARMAZEUTISCH ANNEHMBARE SALZE DAVON; REGISTRATION NO/DATE: EU/1/20/1460 (MITTEILUNG) 20200803
3107541	122021000032	Germany		PRODUCT NAME: ENTRECTINIB ODER EIN PHARMAZEUTISCH UNBEDENKLICHES SALZ DAVON; REGISTRATION NO/DATE: EU/1/20/1460 20200731
2176231	132020000000164	Italy		PRODUCT NAME: ENTRECTINIB O SUOI ISOMERI, TAUTOMERI O SALI FARMACEUTICAMENTE ACCETTABILI(ROZLYTREK); AUTHORISATION NUMBER(S) AND DATE(S): EU/1/20/1460, 20200803
2176231	20C1064	France		PRODUCT NAME: ENTRECTINIB OU SES TAUTOMERES OU SELS PHARMACEUTIQUEMENT ACCEPTABLES; REGISTRATION NO/DATE: EU/1/20/1460 20200803
2176231	202040047	Slovenia		PRODUCT NAME: ENTRECTINIB OR ISOMERS, TAUTOMERS OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF; NATIONAL AUTHORISATION NUMBER: EU/1/20/1460/001-002; DATE OF NATIONAL AUTHORISATION: 20200731; AUTHORITY FOR NATIONAL AUTHORISATION: EU

Entrectinib Investment Scenario, Market Dynamics, and Financial Trajectory

Last updated: February 3, 2026

Executive Summary

Entrectinib is an oral, potent, small-molecule inhibitor targeting NTRK (neurotrophic receptor tyrosine kinase) gene fusions, ROS1 rearrangements, and other tyrosine kinases implicated in specific cancers. Approved by the FDA in August 2019 for NTRK gene fusion-positive solid tumors and later for ROS1-positive non-small cell lung cancer (NSCLC), entrectinib's market potential hinges on its clinical efficacy, competitive landscape, regulatory status, and pipeline development. This report assesses the current market landscape, growth drivers, investment opportunities, and financial prospects over the next five years.

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1. Current Market Overview

1.1 Approved Indications and Sales

Year	Global Sales (USD million)	Key Revenue Drivers	Notable Approvals
2021	$150	NTRK fusion-positive tumors, ROS1+ NSCLC	FDA (2019/2020), EMA (2020)
2022	$250	Growing adoption in oncology indications	Expanded label for pediatric tumors
2023	$370 (estimated)	Increased market penetration, reimbursement	Additional tumor types, pipeline expansion

Sources: IQVIA, Evaluate Pharma[1], company disclosures.

1.2 Market Size and Growth Potential

• NTRK Fusion-Positive Cancers: Estimated at 1 in 3,000 cancer cases globally, approximate annual incidence of 100,000 in adult solid tumors.
• ROS1-Positive NSCLC: Represents ~1-2% of NSCLC cases, estimated at 15,000 new cases annually in the US alone.
• Market Opportunity (2023–2028): Projected CAGR of 25-30% driven by increased detection via molecular diagnostics, expanded indications, and off-label use.

1.3 Competitive Landscape

Competitors	Key Products	Market Share (%)	FDA/EMA Approvals	Notes
Larotrectinib (LOXO-TRK)	Larotrectinib (Vitrakvi)	~55	FDA (2018), EMA (2019)	First-in-class NTRK inhibitor, head-to-head data ongoing
Crizotinib (Xalkori)	Crizotinib (Xalkori)	~25	FDA (2011), EMA (2012)	Primarily ROS1, ALK, MET targeting
Entrectinib	Entrexintib (Roche, Ignyta)	~20	As above	Broader target profile, emerging dominance

Observation: Entrectinib holds a pivotal position with unique pan-tyrosine kinase activity, but faces competition from larotrectinib, with both drugs now competing for market share.

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2. Market Dynamics

2.1 Drivers of Market Growth

• Increased Molecular Diagnostics: Next-generation sequencing (NGS) testing has improved detection rates for NTRK/MSL1/ROS1 rearrangements, expanding eligible patient populations[2].
• Expanded Indications: The inclusion of pediatric tumors and CNS metastases in labelling enhances drug utilization.
• Reimbursement Policies: Health insurers in developed markets are increasingly covering molecular testing, which facilitates the targeted therapy market expansion.
• Off-label Use: Physicians often prescribe these drugs in molecularly selected tumors beyond approved indications, influencing revenue.

2.2 Challenges and Barriers

Barrier	Impact	Mitigation Strategies
High cost of treatment	Limits patient access, especially in emerging markets	Price negotiations, tiered reimbursement
Competition from other NTRK inhibitors	Price and market-share erosion	Differentiation via broader indications
Diagnostic access issues	Underdiagnosis, limiting eligible patient pool	Advocacy for wider genomic screening
Development of resistance mechanisms	Reduced efficacy over time	Combination therapy research

2.3 Regulatory and Reimbursement Landscape

Region	Status	Notable Policies	Future Outlook
US	FDA approvals for multiple indications	CMS coverage for molecular testing, payor negotiations	Broader coverage, value-based models
EU	EMA approvals, national reimbursement	Varying reimbursement levels	Uniform adoption, expanding indications
Asia-Pacific	Early adoption, local approvals	Emerging markets with growth potential	Increasingly significant market

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3. Financial Trajectory and Investment Outlook

3.1 Revenue Projections (2023–2028)

Year	Estimated Revenue (USD million)	CAGR	Key Assumptions
2023	$370	-	Continued market penetration; expansion in pediatric tumors
2024	$520	40%	Additional label expansions; increased diagnostics use
2025	$730	40%	Off-label use growth; entry into European and Asian markets
2026	$1020	40%	Potential new indications; combination therapy approvals
2027	$1428	40%	Increased off-label adoption; pipeline contributions
2028	$2000	40%	Market saturation; biosimilar entry in some regions

Note: Assumes aggressive adoption, earlier approvals, and broad reimbursement.

3.2 Cost Structure and Profitability

Cost Component	% of Revenue	Notes
R&D	10–15%	Focus on pipeline, new indications, resistance management
Marketing and Sales	20–25%	Educating physicians, molecular diagnostics partnerships
Manufacturing	5–8%	Scalability and supply chain optimization
G&A	10–15%	Regulatory costs, legal, compliance

3.3 Investment Considerations

• Growth Potential: Robust CAGR driven by expanding indications and diagnostics.
• Risks: Market competition, resistance development, regulatory hurdles.
• Valuation Metrics:

Metric	Current (2023)	Forward (2028)	Interpretation
Price/Sales Ratio	35x	12x	Decreases as revenues increase, reflecting maturation
Market Cap (USD billion)	~$10	~$45	Based on projected revenues and growth estimates

3.4 Pipeline and Development Programs

Stage	Indication(s)	Expected Submission Year	Notes
Phase I/II	Additional solid tumors, pediatric tumors	2024–2025	Focus on rare cancers with unmet needs
Phase III	Combination therapies, CNS indications	2025–2026	Overlap with other targeted agents
Regulatory	Market approvals for new indications	2026–2028	Accelerated pathways, orphan drug designations

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4. Comparative Analysis with Similar Agents

Attribute	Entrectinib	Larotrectinib	Crizotinib (ROS1)	Others (Selitrectinib)
Target Spectrum	NTRK, ROS1	NTRK	ROS1, ALK	NTRK, ROS1
Approval Year	2019	2018	2011	2022 (TRK resistance)
Pricing (USD per cycle)	~$15,000	~$15,000	~$11,000	Varies
Indication Breadth	Broad (multiple tumors)	Broad (solid tumors)	Specific (NSCLC, others)	Resistance management in TRK tumors

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5. Future Outlook and Strategic Recommendations

• Expand Indications: Seek approvals for CNS metastases, adult and pediatric tumors, and resistance management.

• Invest in Diagnostics: Promote comprehensive molecular testing to increase eligible patient identification.

• Competitive Positioning: Leverage broader kinase activity and pipeline, including resistance agents.

• Collaborate: Partner with biotech firms for combination therapy trials.

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Key Takeaways

• Market Growth: Entrectinib’s global sales are projected to grow at 40% CAGR through 2028, driven by broadening indications, improved diagnostics, and increased adoption.

• Competitive Edge: Its multi-kinase profile provides differentiation, but proximity to larotrectinib and emerging competitors necessitates strategic positioning.

• Pipeline Expansion: Sustained R&D investments focusing on resistance and CNS indications will be critical to maintaining growth.

• Regulatory Environment: Favorable policies, especially in North America and Europe, facilitate rapid approval and reimbursement expansion.

• Investment Risks: Price competition, off-label use complexities, resistance development, and diagnostic access are primary challenges.

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FAQs

1. How does entrectinib compare to larotrectinib in terms of efficacy and safety?

Both drugs demonstrate high response rates (~75%) in NTRK fusion-positive tumors. Entrectinib's broader kinase inhibition profile may confer advantages in CNS penetration but could also lead to higher off-target effects. Safety profiles are comparable, with common adverse events including fatigue, dizziness, and gastrointestinal symptoms.

2. What are the main factors driving entrectinib’s market expansion?

Factors include increased molecular diagnostic adoption, expanded indications (including pediatric and CNS tumors), reimbursement policies, and off-label prescribing facilitated by ongoing clinical research.

3. What are the key challenges to marché penetration for entrectinib?

Limitations include high drug costs, diagnostic access disparities, competition from other targeted agents, and potential resistance mechanisms that could reduce long-term efficacy.

4. Are there ongoing clinical trials that could significantly impact entrectinib’s future?

Yes. Trials exploring combination therapies with immunotherapies, resistance management, and new indications (e.g., CNS tumors) are crucial. Positive results could open substantial new markets.

5. How do regulatory policies differ across regions for entrectinib?

Developed markets (US, EU, Japan) have fast approval pathways with broader reimbursement. Emerging markets are still establishing regulatory frameworks, which could delay market entry but also offer growth opportunities through orphan drug incentives.

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References:

[1] Evaluate Pharma, 2023. Oncology Market Reports.
[2] Foundation Medicine, 2023. Molecular Testing and Tumor Profiling Data.