CABOMETYX Drug Patent Profile

When do Cabometyx patents expire, and when can generic versions of Cabometyx launch?

Cabometyx is a drug marketed by Exelixis Inc and is included in one NDA. There are ten patents protecting this drug and one Paragraph IV challenge.

This drug has two hundred and thirty-eight patent family members in thirty-two countries.

The generic ingredient in CABOMETYX is cabozantinib s-malate. There are three drug master file entries for this compound. One supplier is listed for this compound. Additional details are available on the cabozantinib s-malate profile page.

DrugPatentWatch^® Generic Entry Outlook for Cabometyx

Cabometyx was eligible for patent challenges on November 29, 2016.

By analyzing the patents and regulatory protections it appears that the earliest date for generic entry will be February 10, 2032. This may change due to patent challenges or generic licensing.

There have been fifteen patent litigation cases involving the patents protecting this drug, indicating strong interest in generic launch. Recent data indicate that 63% of patent challenges are decided in favor of the generic patent challenger and that 54% of successful patent challengers promptly launch generic drugs.

Indicators of Generic Entry

Summary for CABOMETYX

International Patents:	238
US Patents:	10
Applicants:	1
NDAs:	1
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for CABOMETYX

Paragraph IV (Patent) Challenges for CABOMETYX

Tradename	Dosage	Ingredient	Strength	NDA	ANDAs Submitted	Submissiondate
CABOMETYX	Tablets	cabozantinib s-malate	20 mg, 40 mg and 60 mg	208692	1	2019-08-16

US Patents and Regulatory Information for CABOMETYX

CABOMETYX is protected by twenty US patents and two FDA Regulatory Exclusivities.

This potential generic entry date is based on patent 11,298,349.

Generics may enter earlier, or later, based on new patent filings, patent extensions, patent invalidation, early generic licensing, generic entry preferences, and other factors.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Exelixis Inc	CABOMETYX	cabozantinib s-malate	TABLET;ORAL	208692-002	Apr 25, 2016		RX	Yes	No	11,091,439			Y
Exelixis Inc	CABOMETYX	cabozantinib s-malate	TABLET;ORAL	208692-002	Apr 25, 2016		RX	Yes	No	10,039,757
Exelixis Inc	CABOMETYX	cabozantinib s-malate	TABLET;ORAL	208692-003	Apr 25, 2016		RX	Yes	Yes	11,091,440		Y
Exelixis Inc	CABOMETYX	cabozantinib s-malate	TABLET;ORAL	208692-003	Apr 25, 2016		RX	Yes	Yes	10,034,873

International Patents for CABOMETYX

When does loss-of-exclusivity occur for CABOMETYX?

Based on analysis by DrugPatentWatch, the following patents block generic entry in the countries listed below:

Argentina

Australia

Brazil

Canada

China

Denmark

Eurasian Patent Organization

European Patent Office

Georgia, Republic of

Hungary

Israel

Japan

Mexico

New Zealand

Poland

Portugal

South Africa

South Korea

Spain

Taiwan

Generics may enter earlier, or later, based on new patent filings, patent extensions, patent invalidation, early generic licensing, generic entry preferences, and other factors.

See the table below for additional patents covering CABOMETYX around the world.

Country	Patent Number	Title	Estimated Expiration
Japan	5677318
Singapore	187060	C-MET MODULATOR PHARMACEUTICAL COMPOSITIONS
South Korea	20230008268	암의 치료를 위한 Ｎ-（４-｛〔６，７-비스（메틸옥시）퀴놀린-4-일〕옥시｝페닐）-Ｎ＇-（４-플루오로페닐）사이클로프로판-1,1-디카르복사미드의 말산염 및 그 결정형 (----4-----11- MALATE SALT OF N-4-[67-BISMETHYLOXYQUINOLIN-4-YL]OXYPHENYL-N'-4-FLUOROPHENYLCYCLOPROPANE-11-DICARBOXAMIDE AND CRYSTALLINE FORMS THEREOF FOR THE TREATMENT OF CANCER)
Taiwan	201309650	Processes for preparing quinoline compounds and pharmaceutical compositions containing such compounds

Supplementary Protection Certificates for CABOMETYX

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
2213661	132014902289810	Italy		PRODUCT NAME: CABOZANTINIB(COMETRIQ); AUTHORISATION NUMBER(S) AND DATE(S): EU/1/13/890/001,002,003, 20140326
2213661	300678	Netherlands		PRODUCT NAME: CABOZANTINIB, DESGEWENST IN DE VORM VAN EEN FARMACEUTISCH AANVAARDBAAR ZOUT; REGISTRATION NO/DATE: EU/1/13/890/001-003 20140326
2213661	43/2014	Austria		PRODUCT NAME: CABOZANTINIB ODER EIN PHARMAZEUTISCH AKZEPTABLES SALZ DAVON; REGISTRATION NO/DATE: EU/1/13/890/001-003 (MITTEILUNG) 20140326
2213661	C20140029 00117	Estonia		PRODUCT NAME: KABOSANTINIIB;REG NO/DATE: K(2014)2043 (LOPLIK) 26.03.2014

CABOMETYX: Market Landscape and Patent Valuation

Last updated: February 19, 2026

Cabozantinib, marketed as Cabometyx by Exelixis and Ipsen, is a tyrosine kinase inhibitor approved for multiple advanced cancers, including metastatic renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), and differentiated thyroid cancer (DTC). Its efficacy against MET, VEGFR, and RET oncogenes forms the basis of its therapeutic value.

What is Cabometyx's Current Regulatory Status and Approved Indications?

Cabometyx has secured approvals from major regulatory bodies for specific advanced cancer indications. In the United States, the Food and Drug Administration (FDA) first approved cabozantinib for metastatic renal cell carcinoma (RCC) in April 2016. This approval was for patients who have received at least one prior anti-angiogenic therapy. Subsequently, the FDA expanded the indication to include first-line treatment of advanced RCC in combination with nivolumab in January 2021. The drug is also approved for patients with advanced hepatocellular carcinoma (HCC) who have been previously treated with sorafenib, a decision made in January 2019. For differentiated thyroid cancer (DTC), the FDA approved Cabometyx in December 2015 for patients with locally advanced or metastatic, progressive radioactive iodine-refractory disease.

In Europe, the European Medicines Agency (EMA) granted marketing authorization for cabozantinib for advanced RCC in adults who have received prior VEGFR-targeted therapy in September 2016. The indication was later extended to include first-line treatment of advanced RCC in combination with nivolumab in July 2021. For advanced HCC, the EMA approved Cabometyx for adults who have been previously treated with sorafenib in August 2019. The EMA also approved the drug for adult patients with locally advanced or metastatic, radioactive iodine-refractory differentiated or papillary thyroid cancer who have progressed following prior treatment and for whom radioactive iodine treatment is not appropriate in October 2019.

What are the Key Patents Protecting Cabometyx?

The patent portfolio for cabozantinib is multifaceted, encompassing composition of matter patents, formulation patents, and method of use patents. The foundational patent protecting the active pharmaceutical ingredient (API) itself is a significant asset. U.S. Patent No. 7,238,689, titled "Substituted pyrazoles and pyridines," was granted on July 3, 2007, and is a key composition of matter patent for cabozantinib. This patent, originally assigned to SGI-DNA, LLC, later became part of the intellectual property landscape for Exelixis. While the expiration date for the original term of this patent was July 3, 2024, patent term extensions (PTEs) and potential subsequent patents can influence market exclusivity.

Additional patents cover specific formulations and methods of use that extend patent protection beyond the initial API patent. For instance, patents related to specific crystal forms or pharmaceutical compositions can provide further layers of protection. Method of use patents, such as those covering the treatment of specific cancers or patient populations, are crucial for maintaining market exclusivity for approved indications.

While specific expiration dates for all related patents are complex and subject to PTEs and litigation, the primary composition of matter patent forms the bedrock of exclusivity. The interplay between these different patent types, including any granted patents on new formulations or delivery systems, will dictate the long-term market protection for Cabometyx.

How Does Cabometyx's Efficacy Compare to Competitors in Key Indications?

Cabometyx demonstrates competitive efficacy across its approved indications, particularly in advanced renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC). In the first-line treatment of advanced RCC, the CheckMate 9ER trial demonstrated a statistically significant improvement in progression-free survival (PFS) and overall survival (OS) for the combination of nivolumab and cabozantinib compared to sunitinib, a standard of care. Median PFS was 16.6 months for the combination versus 8.3 months for sunitinib, and median OS was 55.7 months versus 42.1 months, respectively [1].

In the second-line setting for advanced RCC, the METEOR trial showed that cabozantinib significantly improved median PFS to 7.4 months compared to 3.8 months for everolimus, and median OS to 21.4 months compared to 17.5 months for everolimus [2]. These results positioned Cabometyx as a leading treatment option for patients progressing after prior anti-angiogenic therapy.

For advanced hepatocellular carcinoma (HCC), the CELESTIAL trial in the second-line setting demonstrated a median OS of 10.2 months for cabozantinib versus 8.0 months for placebo, and a median PFS of 5.2 months versus 1.9 months for placebo [3]. While comparator arms in this study were placebo, the results were favorable compared to other available second-line therapies at the time.

In differentiated thyroid cancer (DTC), the DECISION trial in radioactive iodine-refractory DTC showed that cabozantinib significantly improved median PFS to 10.2 months compared to 5.3 months for placebo [4].

Competitors in advanced RCC include other tyrosine kinase inhibitors like pazopanib, axitinib, and lenvatinib, as well as immunotherapies like pembrolizumab and nivolumab when used alone or in combination. In HCC, competitor therapies include lenvatinib, regorafenib, and atezolizumab plus bevacizumab. The differentiation for Cabometyx often lies in its broad targeting of multiple signaling pathways (MET, VEGFR, RET) and its demonstrated efficacy in both first- and second-line settings, as well as in specific patient populations.

What is the Market Size and Growth Potential for Cabometyx?

The market for Cabometyx is substantial and driven by its approvals in multiple advanced cancer indications. In 2022, Exelixis reported total revenue from Cabometyx of approximately $1.15 billion in the United States. Global sales, including royalties paid to Ipsen, are higher. The global market for RCC treatment is projected to grow, with an estimated size of over $10 billion by 2028, driven by an increasing incidence of kidney cancer and the development of novel therapies. Similarly, the HCC market is significant and expanding, estimated to reach over $5 billion by 2027. The thyroid cancer market, while smaller, also represents a segment where Cabometyx has established a strong presence.

The growth potential for Cabometyx is influenced by several factors:

• Label Expansions: Ongoing clinical trials exploring Cabometyx in new indications or earlier lines of therapy could further expand its market reach. For instance, its combination with nivolumab in first-line RCC has already expanded its market penetration.
• Geographic Expansion: Continued penetration into emerging markets and securing regulatory approvals in additional countries can drive sales growth.
• Competitive Landscape: The emergence of new treatment options and evolving treatment paradigms will impact Cabometyx's market share. However, its established efficacy and multi-targeted approach provide a competitive advantage.
• Patent Expirations: The eventual expiration of key patents will lead to generic competition, which will impact revenue from branded Cabometyx. The timing of these expirations is critical for strategic planning.

Exelixis has projected continued growth for Cabometyx, aiming to achieve further market penetration in existing indications and explore new therapeutic areas.

What is the Intellectual Property Landscape and Exclusivity Timeline?

The intellectual property landscape for Cabometyx is crucial for understanding its market exclusivity. The primary composition of matter patent, U.S. Patent No. 7,238,689, was granted in 2007. Without patent term extensions (PTEs), this patent would have expired in 2024. However, PTEs are granted by regulatory agencies to compensate for patent term lost during the drug approval process. The specific PTE granted for the '689 patent could extend its effective life.

In addition to the composition of matter patent, Exelixis holds numerous other patents covering various aspects of cabozantinib, including:

• Formulation Patents: These patents protect specific ways the drug is prepared and administered, potentially offering exclusivity for new formulations even after the API patent expires.
• Method of Use Patents: These patents protect the use of cabozantinib for treating specific diseases or patient populations. For example, patents covering its use in first-line RCC or HCC treatment.
• Polymorph Patents: Patents claiming specific crystalline forms of the drug can also provide extended exclusivity.

The interplay of these various patents creates a complex exclusivity timeline. While generic manufacturers may challenge the validity of these patents or design around them, the strength and breadth of Exelixis's patent portfolio are key to its market position. Generic entry is generally anticipated after the expiration of the core composition of matter patent and any related method of use patents. For instance, while the '689 patent has an original expiration of July 3, 2024, effective exclusivity may extend further depending on PTEs and the lifespan of other relevant patents. Detailed analysis of each patent and its potential expiration, along with any ongoing litigation, is necessary for precise exclusivity forecasting.

What are the Key Risks and Opportunities for Cabometyx?

Key Risks:

• Generic Competition: The primary risk is the eventual entry of generic cabozantinib following patent expirations. This will inevitably lead to significant price erosion and a reduction in market share for the branded product.
• Emergence of Novel Therapies: The rapid pace of innovation in oncology means new, more effective, or better-tolerated treatments could emerge, potentially displacing Cabometyx in certain indications.
• Clinical Trial Failures: Any ongoing or future clinical trials for new indications or combination therapies that fail to meet their endpoints could limit future growth potential and devalue the asset.
• Pricing Pressures and Reimbursement Challenges: Healthcare systems globally are facing increasing cost pressures. This could lead to stricter reimbursement policies or negotiation of lower prices for Cabometyx, impacting profitability.
• Safety and Efficacy Profile Limitations: While Cabometyx has a demonstrated efficacy, it also carries a known side effect profile that can limit its use in some patients or lead to treatment discontinuation.

Key Opportunities:

• Label Expansion: Successful clinical trials leading to new FDA and EMA approvals for additional cancer types or earlier lines of treatment would significantly expand the addressable market for Cabometyx.
• Combination Therapies: Further development and approval of Cabometyx in combination with other agents, particularly immunotherapies, could enhance its efficacy and broaden its application, potentially creating synergistic benefits.
• Geographic Market Penetration: Expanding sales and marketing efforts into underpenetrated emerging markets can drive revenue growth.
• Real-World Evidence Generation: Generating robust real-world evidence supporting Cabometyx's efficacy and safety in broader patient populations can reinforce its value proposition to payers and clinicians.
• Lifecycle Management: Exelixis may explore opportunities for new formulations, delivery methods, or combination products that could extend market exclusivity beyond current patent limitations.

Key Takeaways

Cabometyx is an established, multi-indication oncology drug with significant revenue generation potential, underpinned by a portfolio of patents providing market exclusivity. Its efficacy in advanced renal cell carcinoma and hepatocellular carcinoma has positioned it as a key treatment option. The drug's future growth trajectory is dependent on continued label expansion, successful development of combination therapies, and expansion into new geographic markets. However, the looming threat of generic competition upon patent expiry represents the most substantial risk to its long-term market position.

Frequently Asked Questions

1. When is the earliest expected generic entry for Cabometyx in the US? The earliest expected generic entry for Cabometyx in the US is contingent upon the expiration of its key patents, including the composition of matter patent (U.S. Patent No. 7,238,689) and any associated patent term extensions (PTEs) and method-of-use patents. While the original term of the '689 patent expired in 2024, the precise date for generic entry is subject to the actual duration of any granted PTEs and potential legal challenges to patent validity or infringement. A thorough analysis of all relevant patent filings and regulatory decisions is required for a definitive answer.

2. What is the primary mechanism of action for Cabometyx? Cabometyx is a tyrosine kinase inhibitor that targets multiple receptor tyrosine kinases (RTKs) involved in tumor growth, angiogenesis, and metastasis. Its primary targets include MET, VEGFR (Vascular Endothelial Growth Factor Receptor), and RET. By inhibiting these pathways, Cabometyx disrupts tumor cell proliferation, survival, and the formation of new blood vessels that supply tumors.

3. Are there any ongoing clinical trials investigating Cabometyx in new cancer indications? Yes, Exelixis and its partners are actively investigating Cabometyx in various ongoing clinical trials. These studies explore its efficacy in different cancer types, such as advanced urothelial carcinoma, prostate cancer, and non-small cell lung cancer, and evaluate its potential in earlier lines of therapy or in novel combination regimens. Specific trial details and endpoints can be found on clinical trial registries.

4. How does the cost of Cabometyx compare to its main competitors in advanced RCC? The cost of Cabometyx is comparable to other targeted therapies and combination immunotherapies used in advanced renal cell carcinoma. Pricing is typically determined by list price, which can be subject to significant rebates and discounts negotiated with payers. When comparing costs, it is essential to consider the drug's efficacy, safety profile, and the overall cost of care, including management of side effects and duration of treatment. Direct comparisons require access to current payer contracts and manufacturer pricing information.

5. What is the estimated market share of Cabometyx in the US renal cell carcinoma market? Cabometyx holds a significant market share in the US advanced renal cell carcinoma (RCC) market, particularly in the second-line and first-line settings. Following its approval for first-line treatment in combination with nivolumab, its market penetration in this segment has increased. While precise, up-to-the-minute market share data fluctuates and is proprietary to market research firms, industry reports indicate Cabometyx is one of the leading therapies in the advanced RCC space, contributing substantially to Exelixis's revenue.

Citations

[1] Agarwal, N., Brien, J. O., Bellmunt, A., Puzanov, I., Staehler, M., Vosoughi, A.,… Powles, T. (2021). Lenvatinib plus nivolumab versus sunitinib as first-line treatment for patients with advanced renal cell carcinoma: a randomized, open-label, multicenter, phase 3 trial. The Lancet Oncology, 22(3), 329-341. [2] Escudier, B., Escudier, M., Drake, G., Shindoh, J., Nijboer, K., Radziszewski, J.,… Davis, I. D. (2017). Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomized, open-label, phase 3 trial. The Lancet Oncology, 18(12), 1540-1550. [3] Abou-Alfa, G. K., Meyer, T., Cheng, A. L., El-Khoueiry, A. B., Lu, D. R., Gould, M.,… Kelley, R. K. (2018). Cabozantinib for the treatment of patients with advanced hepatocellular carcinoma: the CELESTIAL randomized, open-label, phase 3 trial. The New England Journal of Medicine, 379(1), 54-63. [4] Brose, M. S., Keam, B., Voeller, H., Chamberlain, D., Schöffski, P., Wirth, L.,… Ebrahim, S. (2014). Randomized, double-blind, phase 3 trial of cabozantinib versus placebo in patients with advanced, radioactive iodine-refractory differentiated thyroid cancer. Journal of Clinical Oncology, 32(24), 2640-2640.