STIVARGA Drug Patent Profile

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

Stivarga is a drug marketed by Bayer Hlthcare and is included in one NDA. There are four patents protecting this drug and one Paragraph IV challenge.

The generic ingredient in STIVARGA is regorafenib. There is one drug master file entry for this compound. One supplier is listed for this compound. Additional details are available on the regorafenib profile page.

DrugPatentWatch^® Generic Entry Outlook for Stivarga

Stivarga was eligible for patent challenges on September 27, 2016.

By analyzing the patents and regulatory protections it appears that the earliest date for generic entry will be April 8, 2031. This may change due to patent challenges or generic licensing.

There have been eight 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 STIVARGA

US Patents:	4
Applicants:	1
NDAs:	1
Finished Product Suppliers / Packagers:	1
Raw Ingredient (Bulk) Api Vendors:	98
Clinical Trials:	84
Patent Applications:	6,422
Drug Prices:	Drug price information for STIVARGA
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for STIVARGA
What excipients (inactive ingredients) are in STIVARGA?	STIVARGA excipients list
DailyMed Link:	STIVARGA at DailyMed

See drug prices for STIVARGA

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

NDA:

203085

Dosage:

TABLET;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.

Recent Clinical Trials for STIVARGA

Identify potential brand extensions & 505(b)(2) entrants

Sponsor	Phase
Asan Medical Center	PHASE1
Mirror Biologics, Inc.	PHASE2
Great Novel Therapeutics Biotech & Medicals Corporation	Phase 1/Phase 2

See all STIVARGA clinical trials

Pharmacology for STIVARGA

Drug Class	Kinase Inhibitor
Mechanism of Action	Breast Cancer Resistance Protein Inhibitors Cytochrome P450 2C9 Inhibitors Kinase Inhibitors UGT1A1 Inhibitors UGT1A9 Inhibitors

Paragraph IV (Patent) Challenges for STIVARGA

Tradename	Dosage	Ingredient	Strength	NDA	ANDAs Submitted	Submissiondate
STIVARGA	Tablets	regorafenib	40 mg	203085	2	2016-09-27

US Patents and Regulatory Information for STIVARGA

STIVARGA is protected by four US patents.

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
Bayer Hlthcare	STIVARGA	regorafenib	TABLET;ORAL	203085-001	Sep 27, 2012		RX	Yes	Yes
Bayer Hlthcare	STIVARGA	regorafenib	TABLET;ORAL	203085-001	Sep 27, 2012		RX	Yes	Yes			Y	Y
Bayer Hlthcare	STIVARGA	regorafenib	TABLET;ORAL	203085-001	Sep 27, 2012		RX	Yes	Yes			Y
Bayer Hlthcare	STIVARGA	regorafenib	TABLET;ORAL	203085-001	Sep 27, 2012		RX	Yes	Yes				Y

Expired US Patents for STIVARGA

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	Patent No.	Patent Expiration
Bayer Hlthcare	STIVARGA	regorafenib	TABLET;ORAL	203085-001	Sep 27, 2012

EU/EMA Drug Approvals for STIVARGA

Company	Drugname	Inn	Product Number / Indication	Status	Generic	Biosimilar	Orphan	Marketing Authorisation	Marketing Refusal
Bayer Pharma AG	Stivarga	regorafenib	EMEA/H/C/002573Stivarga is indicated as monotherapy for the treatment of adult patients with:metastatic colorectal cancer (CRC) who have been previously treated with, or are not considered candidates for, available therapies - these include fluoropyrimidine-based chemotherapy, an anti-VEGF therapy and an anti-EGFR therapy;unresectable or metastatic gastrointestinal stromal tumors (GIST) who progressed on or are intolerant to prior treatment with imatinib and sunitinib;hepatocellular carcinoma (HCC) who have been previously treated with sorafenib.	Authorised	no	no	no	2013-08-26

International Patents for STIVARGA

When does loss-of-exclusivity occur for STIVARGA?

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

Argentina

Australia

Brazil

Canada

Chile

China

Colombia

Costa Rica

Croatia

Cuba

Denmark

Dominican Republic

Ecuador

European Patent Office

Guatemala

Hong Kong

Hungary

Israel

Japan

Jordan

Malaysia

Mexico

Morocco

New Zealand

Peru

Philippines

Poland

Portugal

Russian Federation

Serbia

Singapore

Slovenia

South Korea

Spain

Taiwan

Tunisia

Ukraine

Uruguay

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 STIVARGA around the world.

Country	Patent Number	Title	Estimated Expiration
Argentina	035310	DIFENILUREAS SUBSTITUIDAS CON OMEGA CARBOXIARILO COMO INHIBIDORES DE RAF QUINASA; SUS COMPOSICIONES FARMACEUTICAS Y UN METODO PARA EL TRATAMIENTO DEL CRECIMIENTO DE CELULAS CANCEROSAS
Argentina	077485	DIFENILUREAS SUBSTITUIDAS CON CARBOXIARILO COMO INHIBIDORES DE RAF QUINASA
Austria	321027
Austria	460398
Austria	520663
Austria	538794
Austria	556713

Supplementary Protection Certificates for STIVARGA

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
1140840	91280	Luxembourg		91280, EXPIRES: 20210720
1140840	PA2006008	Lithuania		PRODUCT NAME: SORAFENIBAS IR FARMACINIU POZIURIU PRIIMTINOS JO DRUSKOS; REGISTRATION NO/DATE: EU/1/06/342/001 20060719
1140840	300242	Netherlands
1140840	06C0034	France		PRODUCT NAME: SORAFENIB TOSYLATE, ET AUTRES SELS PHARMACEUTIQUEMENT ACCEPTABLES DE SORAFENIB; REGISTRATION NO/DATE IN FRANCE: EU/1/06/342/001 DU 20060719; REGISTRATION NO/DATE AT EEC: EU/1/06/342/001 DU 20060719
1140840	CA 2007 00002	Denmark		PRODUCT NAME: SORAFENIB TOSYLAT
1140840	SPC 031/2006	Ireland		SPC 031/2006: 20070528, EXPIRES: 20210718
1140840	PA2006008,C1140840	Lithuania		PRODUCT NAME: SORAFENIBAS IR FARMACINIU POZIURIU PRIIMTINOS JO DRUSKOS; REGISTRATION NO/DATE: EU/1/06/342/001 20060719

Stivarga (Regorafenib) Market Dynamics, Patent Exclusivity, and Financial Trajectory

Last updated: September 25, 2026

Stivarga is Bayer’s oral multikinase inhibitor regorafenib, approved in the United States for previously treated metastatic colorectal cancer, advanced gastrointestinal stromal tumors, and hepatocellular carcinoma. Its commercial profile is mature but durable: sales have remained around the €1 billion annual range, supported by three indications and global availability. The main future risks are generic entry, pricing pressure, competing targeted therapies, and the decline of its original colorectal cancer franchise.

What is Stivarga and how does it work?

Stivarga contains regorafenib, a small-molecule kinase inhibitor that targets multiple signaling pathways involved in tumor growth, angiogenesis, and the tumor microenvironment.

Attribute	Stivarga data
Active ingredient	Regorafenib
Developer and marketer	Bayer AG
Drug class	Oral multikinase inhibitor
U.S. approval	September 27, 2012
Dosage form	40 mg tablets
Standard dose	160 mg once daily for the first 21 days of a 28-day cycle
U.S. indications	Metastatic colorectal cancer, GIST, hepatocellular carcinoma
Primary competitors	Lonsurf, Fruzaqla, Cabometyx, Nexavar and generic multikinase therapies
Regulatory pathway	New drug application
Biosimilar exposure	None; regorafenib is a chemically synthesized small molecule

The approved dose is frequently reduced because of hand-foot skin reaction, fatigue, diarrhea, hypertension, hepatotoxicity, and other treatment-related toxicities. Dose interruptions and reductions affect persistence and net revenue per patient (U.S. Food and Drug Administration [FDA], 2020).

What are Stivarga’s approved indications and commercial markets?

Metastatic colorectal cancer

Stivarga was first approved for patients with metastatic colorectal cancer previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and, where appropriate, an anti-EGFR therapy.

This indication established the product but is now highly competitive. Lonsurf, a trifluridine/tipiracil product from Taiho and Servier, competes directly in later-line colorectal cancer. Takeda’s Fruzaqla, or fruquintinib, received FDA approval in 2023 for previously treated metastatic colorectal cancer and has a more selective VEGFR profile. Fruzaqla’s entry increases pressure on Stivarga prescribing and reimbursement, particularly in U.S. oncology practices.

Gastrointestinal stromal tumors

Stivarga is approved for patients with unresectable or metastatic GIST who previously received imatinib and sunitinib. The GIST market is smaller than colorectal cancer but provides a differentiated use after two established kinase inhibitors.

The main commercial alternatives include Qinlock, or ripretinib, from Deciphera Pharmaceuticals, and continued use of kinase inhibitors in molecularly selected disease. GIST remains relevant to Stivarga because treatment sequencing and physician familiarity support continued use after progression.

Hepatocellular carcinoma

Stivarga is approved for patients with hepatocellular carcinoma previously treated with sorafenib. This indication extended the product’s life cycle beyond colorectal cancer and GIST.

The HCC market has changed materially since the approval. Combination immunotherapy, including atezolizumab plus bevacizumab and durvalumab plus tremelimumab, has displaced sorafenib in many first-line settings. Stivarga remains a later-line option, but its use depends on prior treatment selection, liver function, tolerability, and regional treatment guidelines.

How has Stivarga revenue changed over time?

Stivarga has maintained unusually stable revenue for a mature oncology product. Bayer reports product sales by brand and region, while currency translation can materially affect year-to-year comparisons.

Fiscal year	Approximate Bayer Stivarga sales	Commercial interpretation
2020	About €1.0 billion	Mature global franchise
2021	About €1.0 billion	Stable demand despite COVID-19 effects
2022	About €1.0 billion	Resilient sales across established indications
2023	About €1.0 billion	Continued maturity and competitive pressure
2024	Approximately €1.0 billion range	Sustained revenue before broader generic erosion

The exact reported amount varies by Bayer’s reporting currency, exchange rates, regional accounting, and annual-report presentation. Stivarga has not followed the steep decline typical of a single-indication oncology product because Bayer expanded the label into GIST and HCC and maintained use in multiple international markets (Bayer AG, 2021, 2022, 2023, 2024).

What explains Stivarga’s revenue resilience?

Stivarga’s revenue has been supported by four factors:

1. It treats later-line disease with limited alternatives.
2. The product has three FDA-approved oncology indications.
3. Oncology pricing remains high even when treatment duration is relatively short.
4. Bayer has retained global commercial control and established reimbursement infrastructure.

The principal constraints are toxicity, treatment discontinuation, competition from newer agents, and generic substitution once enforceable U.S. protection expires.

When does Stivarga lose exclusivity?

Stivarga has already lost several forms of non-patent exclusivity.

Exclusivity type	Status
U.S. new chemical entity exclusivity	Expired in 2017
Orphan-drug exclusivity for GIST	Expired
Orphan-drug exclusivity for HCC	Expired
Pediatric exclusivity	Any applicable period has expired or is no longer commercially material
Patent protection	Dependent on individual Orange Book-listed patents and jurisdiction
Generic launch timing	Controlled by surviving patents, litigation, settlement terms, and FDA approval

The first U.S. approval occurred in 2012, so five-year new chemical entity exclusivity ended in 2017. Orphan-drug exclusivity also protected certain indications for seven years, but those periods have expired. Current commercial protection is therefore patent-based rather than exclusivity-based.

What patents protect Stivarga?

Stivarga’s U.S. protection has included patents covering the regorafenib compound, pharmaceutical compositions, and methods of treating cancer. The relevant estate is more limited than the estate for a recently launched biologic or long-acting formulation.

Bayer’s core patent filings originated in the late 2000s. U.S. patent terms for the principal compound and related patents generally fall in the mid-to-late 2020s, subject to patent-term adjustment, terminal disclaimers, pediatric extensions, and the scope of each Orange Book listing.

Protection category	Strategic role
Regorafenib compound claims	Protect the active pharmaceutical ingredient
Pharmaceutical composition claims	Protect tablet and drug-composition formats
Method-of-use claims	Cover treatment of colorectal cancer, GIST, or HCC
Manufacturing claims	May restrict selected synthetic routes or intermediates
Formulation claims	Provide narrower protection than compound claims and may not block all generic products

The FDA Orange Book remains the controlling public source for listed U.S. patents and expiration information. Patent dates should be assessed patent by patent because the earliest compound patent does not necessarily determine the full commercial blocking period (FDA, 2024).

What is the Orange Book status of Stivarga?

Stivarga is listed in the FDA Orange Book as an approved small-molecule drug. Its Orange Book strategy has historically relied on patents covering the active ingredient and approved uses rather than a complex delivery technology.

A generic applicant seeking approval before expiration of a listed patent must certify under Paragraph IV that the patent is invalid, unenforceable, or would not be infringed. Bayer can file an infringement action within 45 days of receiving notice, potentially triggering a 30-month stay of ANDA approval under the Hatch-Waxman framework.

The commercial significance of each patent depends on whether a generic applicant can use a different formulation, omit a patented indication through a section viii statement, or challenge the patent successfully.

Which companies are challenging Stivarga patents?

Publicly visible generic activity is less central to Stivarga’s market than it is for older high-volume oral drugs such as imatinib or lenalidomide. The relevant potential challengers are generic manufacturers capable of producing regorafenib tablets and filing abbreviated new drug applications.

No biosimilar pathway applies. FDA approval would proceed through an ANDA because regorafenib is a small molecule, not through the biosimilar pathway under the Public Health Service Act.

A definitive assessment of active Paragraph IV litigation requires the current FDA Orange Book, ANDA litigation records, and district-court dockets. Bayer’s public filings have not identified Stivarga as a major current litigation exposure comparable to its highest-profile product liability or patent matters.

What patent litigation and settlement risks affect Stivarga?

The principal litigation risks are:

• Paragraph IV invalidity or non-infringement claims against compound patents.
• Challenges to method-of-use patents.
• Disputes over whether a generic product induces infringement of an approved indication.
• Patent-term adjustment calculations.
• Launch-at-risk activity before final judgment.
• Commercial settlements granting an agreed generic entry date.

A settlement could preserve substantial Stivarga revenue if it delays generic entry beyond the earliest patent expiry. Conversely, an at-risk launch could cause rapid erosion because generic oncology tablets can substitute for the branded product through pharmacy and payer channels.

No broad public settlement has established a universally recognized Stivarga generic-entry date. The economic value of the franchise therefore depends on the enforceability of remaining listed patents and the timing of any ANDA approvals.

How strong is the Stivarga patent estate?

Stivarga has a moderate, declining patent position.

Strengths

• Regorafenib is a defined active ingredient with established clinical use.
• The product has multiple approved indications.
• Compound patents can create a direct barrier to identical generic products.
• The three-indication label creates potential method-of-use and induced-infringement issues.

Weaknesses

• Core protection is mature.
• U.S. chemical patent protection is approaching or entering the normal post-approval erosion period.
• The product has no biologic manufacturing barrier.
• There is no major long-acting formulation or device platform protecting the franchise.
• Generic manufacturers can pursue conventional tablet development.
• The later-line oncology market has several therapeutic substitutes.

Stivarga’s patent estate is stronger than its non-patent exclusivity position but materially weaker than a recently approved product with a new chemical entity period and multiple patent families extending into the 2030s.

What generic entry risks exist for Stivarga?

The most likely generic-launch scenarios are:

Scenario	Market effect
No approved ANDA before core patent expiry	Continued branded revenue, followed by delayed erosion
First generic launches after negotiated settlement	Moderate initial erosion, accelerating as additional suppliers enter
At-risk launch succeeds	Rapid price and volume erosion
Multiple generics launch simultaneously	Severe net-price decline and payer-driven substitution
Patent survives but method-of-use claims narrow entry	Partial generic penetration through non-protected indications

The first generic entrant often receives meaningful commercial advantage, but oncology products can experience rapid price compression after several suppliers enter. Stivarga’s high list price creates substantial payer incentive to substitute, although physician prescribing, specialty pharmacy distribution, and indication-specific use may slow the transition.

How does Stivarga compare with competing drugs?

Product	Company	Main competitive area	Competitive position
Stivarga	Bayer	Later-line CRC, GIST, HCC	Mature multikinase franchise
Lonsurf	Taiho/Servier	Later-line CRC	Established oral alternative
Fruzaqla	Takeda	Later-line CRC	Newer targeted competitor
Qinlock	Deciphera	Advanced GIST	Direct GIST competitor
Nexavar	Bayer	HCC and other cancers	Older Bayer multikinase product
Cabometyx	Exelixis	HCC and other tumors	Competes in selected liver-cancer treatment settings
Immunotherapy combinations	Multiple companies	First-line HCC	Reduces sorafenib and downstream treatment exposure

Fruzaqla is the most important newer colorectal cancer competitor. Qinlock is the clearest direct competitor in GIST. In HCC, the greatest structural pressure comes from first-line immunotherapy combinations, which influence the pool of patients reaching later-line kinase treatment.

What is Stivarga’s geographic coverage?

Bayer markets Stivarga internationally, with approvals in the United States, Europe, Japan, China, and other major oncology markets. The product’s commercial performance varies by country because of:

• National reimbursement decisions.
• Local patent status.
• Generic approval timing.
• Hospital versus retail distribution.
• Treatment guidelines.
• Regional competition.
• Currency fluctuations.

U.S. revenue is strategically important because of high oncology pricing, but the United States is also the market most exposed to Paragraph IV litigation and rapid generic substitution. European erosion may proceed differently because national health systems negotiate prices and generic entry conditions vary by country.

What manufacturing and intellectual-property barriers protect Stivarga?

Regorafenib tablets do not require biologic cell lines, sterile filling, cold-chain distribution, or a complex delivery device. Manufacturing barriers are therefore limited compared with monoclonal antibodies, antibody-drug conjugates, or depot products.

Potential technical barriers include:

• Synthesis and purification of the active ingredient.
• Control of impurities and polymorphic forms.
• Tablet formulation and dissolution performance.
• Bioequivalence in the finished dosage form.
• Compliance with oncology-grade manufacturing standards.

These barriers can delay a generic applicant but are unlikely to create durable protection after core patents expire. The principal barrier remains patent enforcement, not manufacturing complexity.

What licensing deals are associated with Stivarga?

Bayer developed and commercialized regorafenib through a collaboration with Onyx Pharmaceuticals. Amgen later acquired Onyx. The collaboration included commercial and economic rights relating to regorafenib in the United States, while Bayer retained major development and commercialization responsibilities (Amgen, 2013).

The agreement is strategically relevant because royalty and collaboration economics reduce the amount of gross sales retained by Bayer. Public disclosures have not provided a complete current product-level waterfall for all territories and accounting periods.

What is the FDA regulatory status of Stivarga?

Stivarga remains FDA-approved for its three established indications. The product carries significant safety warnings, including severe or fatal hepatotoxicity, hemorrhage, gastrointestinal perforation or fistula, dermatologic toxicity, hypertension, cardiac ischemia or infarction, and reversible posterior leukoencephalopathy syndrome (FDA, 2020).

The regulatory profile supports continued use in carefully selected patients but limits treatment duration and increases monitoring costs. New label expansion would be difficult because later-line oncology standards have changed and competing agents have stronger positions in several disease segments.

Key Takeaways

• Stivarga is a mature Bayer oncology franchise with annual global sales around €1 billion.
• Its revenue durability comes from three approved indications rather than a single dominant market.
• U.S. new chemical entity and orphan-drug exclusivity have expired.
• Remaining commercial protection depends on Orange Book-listed patents, patent-term adjustments, litigation, and settlements.
• The product is exposed to generic competition, not biosimilar competition.
• Fruzaqla pressures Stivarga in colorectal cancer, while Qinlock competes in GIST and immunotherapy combinations reduce later-line HCC exposure.
• The patent estate is moderate but declining, with core protection concentrated in the mid-to-late 2020s.
• Generic entry could produce rapid price erosion because regorafenib is an oral small molecule without a complex manufacturing barrier.
• Bayer’s collaboration with Onyx, now part of Amgen, affects the economics of the franchise.
• Stivarga remains commercially important but has limited long-term growth potential without a new indication or formulation strategy.

FAQs About Stivarga Patent Expiration and Market Competition

When did Stivarga receive FDA approval?

The FDA approved Stivarga on September 27, 2012, for previously treated metastatic colorectal cancer.

Is Stivarga a biologic or a small-molecule drug?

Stivarga is a chemically synthesized small-molecule drug. Generic versions would use the ANDA pathway, not the biosimilar pathway.

Can a generic manufacturer launch Stivarga before all patents expire?

A generic may launch after successful patent invalidity or non-infringement litigation, under a settlement agreement, or at risk before final resolution. Commercial exposure depends on the specific patent claims and litigation status.

Which drug most directly challenges Stivarga in colorectal cancer?

Fruzaqla is the most important newer targeted competitor, while Lonsurf remains an established later-line oral alternative.

Does Stivarga have formulation-patent protection comparable to complex oncology products?

No. Stivarga’s protection is primarily associated with the active ingredient, pharmaceutical compositions, and methods of use. It does not rely on a major device, depot, or biologic manufacturing platform.

References

Amgen Inc. (2013). Annual report pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 for the fiscal year ended December 31, 2012. https://www.amgen.com

Bayer AG. (2021). Annual report 2020. https://www.bayer.com

Bayer AG. (2022). Annual report 2021. https://www.bayer.com

Bayer AG. (2023). Annual report 2022. https://www.bayer.com

Bayer AG. (2024). Annual report 2023. https://www.bayer.com

U.S. Food and Drug Administration. (2020). Stivarga (regorafenib) prescribing information. https://www.accessdata.fda.gov

U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book