LONSURF Drug Patent Profile

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

Lonsurf is a drug marketed by Taiho Oncology and is included in one NDA. There are six patents protecting this drug and one Paragraph IV challenge.

The generic ingredient in LONSURF is tipiracil hydrochloride; trifluridine. There is one drug master file entry for this compound. One supplier is listed for this compound. Additional details are available on the tipiracil hydrochloride; trifluridine profile page.

DrugPatentWatch^® Litigation and Generic Entry Outlook for Lonsurf

A generic version of LONSURF was approved as tipiracil hydrochloride; trifluridine by NATCO on June 13^th, 2023.

Summary for LONSURF

US Patents:	6
Applicants:	1
NDAs:	1
Finished Product Suppliers / Packagers:	1
Raw Ingredient (Bulk) Api Vendors:	15
Clinical Trials:	60
Patent Applications:	837
Drug Prices:	Drug price information for LONSURF
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for LONSURF
What excipients (inactive ingredients) are in LONSURF?	LONSURF excipients list
DailyMed Link:	LONSURF at DailyMed

See drug prices for LONSURF

Recent Clinical Trials for LONSURF

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

Sponsor	Phase
Kahr Bio Australia Pty Ltd	PHASE2
Novotech (Australia) Pty Limited	PHASE2
Servier	PHASE2

See all LONSURF clinical trials

Pharmacology for LONSURF

Drug Class	Nucleoside Analog Antiviral Nucleoside Metabolic Inhibitor Thymidine Phosphorylase Inhibitor
Mechanism of Action	Nucleic Acid Synthesis Inhibitors Thymidine Phosphorylase Inhibitors

Paragraph IV (Patent) Challenges for LONSURF

Tradename	Dosage	Ingredient	Strength	NDA	ANDAs Submitted	Submissiondate
LONSURF	Tablets	tipiracil hydrochloride; trifluridine	15 mg/6.14 mg and 20 mg/8.19 mg	207981	4	2019-09-23

US Patents and Regulatory Information for LONSURF

LONSURF is protected by ten US patents and one FDA Regulatory Exclusivity.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Taiho Oncology	LONSURF	tipiracil hydrochloride; trifluridine	TABLET;ORAL	207981-001	Sep 22, 2015	AB	RX	Yes	No
Taiho Oncology	LONSURF	tipiracil hydrochloride; trifluridine	TABLET;ORAL	207981-001	Sep 22, 2015	AB	RX	Yes	No
Taiho Oncology	LONSURF	tipiracil hydrochloride; trifluridine	TABLET;ORAL	207981-002	Sep 22, 2015	AB	RX	Yes	Yes
Taiho Oncology	LONSURF	tipiracil hydrochloride; trifluridine	TABLET;ORAL	207981-002	Sep 22, 2015	AB	RX	Yes	Yes			Y	Y
Taiho Oncology	LONSURF	tipiracil hydrochloride; trifluridine	TABLET;ORAL	207981-001	Sep 22, 2015	AB	RX	Yes	No
Taiho Oncology	LONSURF	tipiracil hydrochloride; trifluridine	TABLET;ORAL	207981-002	Sep 22, 2015	AB	RX	Yes	Yes
Taiho Oncology	LONSURF	tipiracil hydrochloride; trifluridine	TABLET;ORAL	207981-002	Sep 22, 2015	AB	RX	Yes	Yes			Y	Y

Expired US Patents for LONSURF

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	Patent No.	Patent Expiration
Taiho Oncology	LONSURF	tipiracil hydrochloride; trifluridine	TABLET;ORAL	207981-001	Sep 22, 2015
Taiho Oncology	LONSURF	tipiracil hydrochloride; trifluridine	TABLET;ORAL	207981-002	Sep 22, 2015
Taiho Oncology	LONSURF	tipiracil hydrochloride; trifluridine	TABLET;ORAL	207981-002	Sep 22, 2015
Taiho Oncology	LONSURF	tipiracil hydrochloride; trifluridine	TABLET;ORAL	207981-001	Sep 22, 2015

International Patents for LONSURF

When does loss-of-exclusivity occur for LONSURF?

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

Australia

Brazil

Canada

China

Croatia

Cyprus

Denmark

European Patent Office

Georgia, Republic of

Hong Kong

Hungary

Japan

Lithuania

Malaysia

Mexico

Morocco

New Zealand

Philippines

Poland

Portugal

Russian Federation

San Marino

Serbia

Singapore

Slovenia

South Korea

Spain

Taiwan

Ukraine

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 LONSURF around the world.

Country	Patent Number	Title	Estimated Expiration
Australia	2017215825
European Patent Office	3412295
Japan	2021113228
Japan	2023065622
Japan	2025013684
Japan	6882205
Japan	WO2017135412

Supplementary Protection Certificates for LONSURF

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
1849470	PA2017024	Lithuania		PRODUCT NAME: TRIFLURIDINAS/TIPIRACILAS; REGISTRATION NO/DATE: EU/1/16/1096 20160425
1849470	300889	Netherlands		PRODUCT NAME: TRIFLURIDINE IN COMBINATIE MET TIPIRACILHYDROCHLORIDE; REGISTRATION NO/DATE: EU/1/16/1096 20160427
1849470	CA 2017 00036	Denmark		PRODUCT NAME: TRIFLURIDINE IN COMBINATION WITH TIPIRACIL OR A PHARMACEUTICALLY ACCEPTABLE SALT OF TIPIRACIL; REG. NO/DATE: EU/1/16/1096 20160427
1849470	122017000052	Germany		PRODUCT NAME: TRIFLURIDIN IN KOMBINATION MIT TIPIRACIL ODER EINEM SALZ VON TIPIRACIL WIE TIPIRACIL-HYDROCHLORID; REGISTRATION NO/DATE: EU/1/16/1096 20160425
1849470	34/2017	Austria		PRODUCT NAME: TRIFLURIDIN / TIPIRACIL ODER DEREN PHARMAZEUTISCH WIRKSAMEN SALZE; REGISTRATION NO/DATE: EU/1/16/1096 (MITTEILUNG) 20160427
1849470	2017C/028	Belgium		PRODUCT NAME: LONSURF - TRIFLURIDINE/TIPIRACIL; AUTHORISATION NUMBER AND DATE: EU/1/16/1096 20160427
1849470	LUC00036	Luxembourg		PRODUCT NAME: TRIFLURIDINE COMBINEE AU TIPIRACIL OU UN SEL DE TIPIRACIL TEL QUE L'HYDROCHLORURE DE TIPIRACIL; AUTHORISATION NUMBER AND DATE: EU/1/16/1096 20160427

Lonsurf Market Dynamics, Revenue Outlook, Patent Protection and Generic Risk

Last updated: August 11, 2026

Lonsurf, the oral trifluridine/tipiracil combination marketed by Taiho Pharmaceutical and Servier, has shifted from a late-line colorectal and gastric cancer product to a broader colorectal cancer regimen through combination use with bevacizumab. The 2023 FDA approval of Lonsurf plus bevacizumab materially expanded its commercial opportunity and improved treatment-line positioning.

The principal investment variables are adoption of the SUNLIGHT regimen, continued prescribing in metastatic colorectal cancer, payer acceptance of combination therapy, international expansion, and the timing of U.S. generic entry. Lonsurf has small-molecule generic exposure rather than biosimilar exposure. Its core U.S. patent protection reaches the late 2020s, while later method-of-use and formulation protection may support additional litigation and launch-delay opportunities.

What is Lonsurf and how is it used?

Lonsurf contains trifluridine, a nucleoside analog, and tipiracil, a thymidine phosphorylase inhibitor that increases trifluridine exposure. It is administered orally in cycles and is approved for advanced gastrointestinal cancers after prior treatment failure.

Item	Details
Brand	Lonsurf
Active ingredients	Trifluridine and tipiracil
Developer	Taiho Pharmaceutical
U.S. commercial partner	Taiho Oncology
International commercial partner	Servier in multiple territories
FDA formulation	Oral tablets
Initial U.S. approval	September 22, 2015
Initial indication	Metastatic colorectal cancer
Gastric cancer approval	February 2019
Combination approval	Lonsurf plus bevacizumab, August 2, 2023
Therapeutic class	Antineoplastic, oral cytotoxic therapy
Primary competitors	Regorafenib, fruquintinib, trifluridine/tipiracil generics after entry, and other later-line regimens

The current commercial center of gravity is metastatic colorectal cancer. The Lonsurf-bevacizumab combination is approved for adults with metastatic colorectal cancer previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF biologic, and, where appropriate, an anti-EGFR antibody or a checkpoint inhibitor.[1]

How large is the Lonsurf market?

Lonsurf is a global specialty oncology product with annual sales in the tens of billions of Japanese yen. Taiho has reported sustained sales growth as the product expanded across colorectal and gastric cancer indications. The 2023 U.S. combination approval created a second commercial growth phase after the product’s initial late-line launch cycle.

The addressable population is narrower than the population for first-line colorectal cancer drugs, but treatment duration and combination use support meaningful revenue per patient. Patients receiving Lonsurf typically have heavily pretreated metastatic disease and limited alternatives.

Market drivers

The main growth drivers are:

1. Increased use of Lonsurf plus bevacizumab in third-line or later colorectal cancer.
2. Adoption following the SUNLIGHT phase 3 trial.
3. Continued use of Lonsurf monotherapy in patients who cannot receive bevacizumab.
4. International guideline inclusion and reimbursement.
5. Expansion of testing and treatment sequencing in metastatic colorectal cancer.
6. Physician familiarity with an established oral therapy.

The SUNLIGHT trial reported improved overall survival and progression-free survival for Lonsurf plus bevacizumab compared with Lonsurf alone. Median overall survival was 10.8 months with the combination versus 7.5 months with Lonsurf monotherapy. Median progression-free survival was 5.6 months versus 2.4 months.[2]

Market constraints

Lonsurf remains limited by:

• Myelosuppression, particularly neutropenia and anemia.
• Frequent monitoring and dose interruptions.
• A late-line treatment position.
• Competition from regorafenib and fruquintinib.
• The need for intravenous bevacizumab when used in combination.
• Reimbursement friction for combination therapy.
• Dependence on colorectal and gastric cancer treatment volumes.
• Small-molecule generic substitution after patent expiry.

What is the financial trajectory for Lonsurf?

Lonsurf’s financial trajectory has three identifiable phases.

Phase one: initial colorectal cancer launch

The first U.S. approval in 2015 established Lonsurf as an oral option for metastatic colorectal cancer after failure of standard chemotherapy and biologic therapy. Early growth depended on oncologist adoption and the limited treatment options available after progression on fluoropyrimidine, oxaliplatin, irinotecan, anti-VEGF therapy, and anti-EGFR treatment.

Phase two: gastric cancer expansion

The 2019 gastric and gastroesophageal junction cancer approval expanded the product’s commercial base. The indication was supported by the TAGS trial, which showed an overall survival benefit compared with placebo in heavily pretreated patients.[3]

The gastric cancer market is smaller than the global colorectal cancer market, but the approval reduced dependence on one tumor type. It also extended the product’s use among patients with few later-line options.

Phase three: combination-led growth

The 2023 Lonsurf-bevacizumab approval changed the economic profile of the product. The combination demonstrated a clinically meaningful survival benefit and gave physicians a stronger reason to use Lonsurf before exhausting all later-line options.

Taiho’s reported Lonsurf sales have remained in a growth range as the colorectal cancer combination rolled out. The commercial impact is likely to be reflected progressively rather than immediately because uptake depends on:

• Guideline changes.
• Hospital and payer protocols.
• Bevacizumab eligibility.
• Regional reimbursement decisions.
• Physician confidence in treatment sequencing.
• Patient ability to tolerate combination treatment.

The product’s revenue ceiling is higher under combination use, but the combination also increases treatment complexity and total regimen cost.

How does Lonsurf compare with competing colorectal cancer drugs?

Product	Mechanism	Administration	Main commercial advantage	Main limitation
Lonsurf	Trifluridine plus tipiracil	Oral	Established survival benefit; combination with bevacizumab	Myelosuppression; late-line use
Lonsurf plus bevacizumab	Cytotoxic plus anti-VEGF therapy	Oral plus intravenous	SUNLIGHT survival data and guideline momentum	Infusion burden and added toxicity
Stivarga	Regorafenib	Oral	Established colorectal cancer presence	Hand-foot syndrome and tolerability
Fruzaqla	Fruquintinib	Oral	Selective VEGFR activity and newer U.S. launch	Newer market access and reimbursement cycle
TAS-102 generic	Trifluridine plus tipiracil	Oral	Lower price after generic entry	Patent and regulatory timing

Lonsurf’s strongest competitive position is its clinical evidence in combination with bevacizumab. Regorafenib competes on oral convenience but has a different tolerability profile. Fruquintinib creates a newer oral targeted option and may take share in patients who prefer oral therapy or have treatment sequencing that favors a VEGFR inhibitor.

When does Lonsurf lose exclusivity?

Lonsurf does not have a single exclusivity date. Its protection consists of FDA regulatory exclusivity, Orange Book-listed patents, method-of-use claims, formulation claims, and potentially patent-term adjustments or extensions.

Protection category	Commercial significance
New chemical entity exclusivity	Expired after the initial U.S. approval period
Orphan-drug exclusivity	Relevant to specific indications if granted; does not necessarily block all product competition
Composition and combination patents	Protect trifluridine/tipiracil and related pharmaceutical compositions
Method-of-use patents	May cover treatment of colorectal or gastric cancer and specific treatment settings
Combination-treatment patents	May cover use with bevacizumab or treatment sequencing
Regulatory exclusivity for new indication	Can delay approval of certain applications for the protected indication
FDA patent listings	Determine the scope of Paragraph IV certification exposure

The core U.S. patent estate is generally understood to provide protection into the late 2020s, with later patents potentially extending protection for specific uses or combinations into the early 2030s. The commercial effect depends on which patents are listed in the Orange Book, which claims are asserted, and whether a generic applicant challenges them.

The FDA Orange Book, rather than a marketing summary, is the controlling source for current listed patents, expiration dates, and use codes.[4]

What patents protect Lonsurf?

The Lonsurf patent estate is built around several technical layers:

Active pharmaceutical combination

The foundational layer protects the combination of trifluridine and tipiracil, including pharmaceutical compositions and dosing relationships. These claims are more important for a conventional generic because a product containing the same active ingredients would generally need to address the relevant listed patents.

Dosing and administration

Later claims may cover specific dosing schedules, cycle structures, dose reductions, or use in patients with advanced gastrointestinal malignancies. These claims can be narrower than composition claims but may still affect the launch strategy of an abbreviated new drug application.

Method of use

Method-of-use protection can cover Lonsurf treatment in metastatic colorectal cancer, gastric cancer, gastroesophageal junction cancer, or defined post-treatment settings. The Lonsurf-bevacizumab approval creates a separate opportunity for combination-use claims.

Formulation and manufacturing

Formulation and manufacturing patents can protect tablet composition, stability, granulation, impurity control, and production processes. These patents are less likely to block every generic product than a composition patent, but they can increase development and litigation costs.

What is the Orange Book status of Lonsurf?

Lonsurf is an FDA-approved small-molecule drug listed in the Orange Book. Generic applicants may file an ANDA with Paragraph IV certifications against relevant listed patents. A Paragraph IV notice can trigger patent litigation and a statutory 30-month stay of final FDA approval if the patent holder files suit within the applicable period.[5]

The practical Orange Book risks are:

• A generic may challenge core composition patents.
• A generic may seek approval for unpatented indications while carving out patented uses.
• A generic may accept some method-of-use patents and certify Paragraph IV against others.
• A successful carve-out could permit earlier launch than a full-label generic.
• The Lonsurf-bevacizumab indication may create separate use-code and labeling disputes.

Which companies are challenging Lonsurf patents?

No major public U.S. generic challenge has become a central market event comparable to the high-profile patent disputes surrounding larger oncology products. The principal future challengers are likely to be generic manufacturers with oncology portfolios and established ANDA capabilities.

Potential entrants could include large U.S. generic companies such as Teva, Viatris, Sandoz, Sun Pharma, Dr. Reddy’s, and Hikma, although public confirmation of a specific Lonsurf Paragraph IV filing should be tied to an FDA notice, litigation complaint, or court docket.

The absence of a visible challenge does not eliminate launch risk. Generic companies often file confidentially or pursue non-infringement, invalidity, or label-carve-out strategies before a commercial launch becomes public.

What generic entry risks exist for Lonsurf?

Lonsurf is exposed to standard small-molecule generic competition. It does not have the manufacturing complexity of a monoclonal antibody, and its active ingredients can be characterized through conventional pharmaceutical testing.

Earliest-entry scenarios

Scenario	Likely commercial effect
Core patents survive and no settlement occurs	Generic entry waits until the relevant patent barrier expires
Paragraph IV settlement with an agreed launch date	Entry may occur before the latest patent expiry
Core patent invalidated or found not infringed	Earlier generic entry and rapid price erosion
Indication carve-out	Generic competes in selected indications while branded combination use remains protected
Authorized generic launch	Taiho or a partner may limit third-party generic economics
Multiple generic entrants	Faster price erosion and payer substitution

The combination indication may delay full economic erosion if branded Lonsurf retains a protected or commercially differentiated role with bevacizumab. That protection would not necessarily prevent generic substitution for monotherapy indications.

Is Lonsurf exposed to biosimilar competition?

No. Lonsurf is a small-molecule tablet, not a biologic. Biosimilar regulation under the Biologics Price Competition and Innovation Act does not apply. The relevant competitive pathway is an ANDA for a chemically equivalent generic.

Bevacizumab, by contrast, is a biologic with multiple biosimilar competitors. Falling bevacizumab prices could reduce the total cost of the Lonsurf-bevacizumab regimen and support broader combination use. Biosimilar competition could also make anti-VEGF treatment more accessible in markets where combination reimbursement is currently restrictive.

What patent litigation and settlement issues affect Lonsurf?

The main legal issues are likely to involve:

• Validity of composition patents.
• Obviousness challenges to trifluridine/tipiracil combinations.
• Infringement of formulation and dosing claims.
• Scope of method-of-use patents.
• Orange Book use codes for combination therapy.
• Whether a generic can omit protected indications from its label.
• Settlement terms governing the first generic launch date.

A settlement could create a commercially important intermediate outcome. It may preserve brand exclusivity until an agreed date while giving the first challenger a defined entry opportunity. The value of such a settlement depends on the number of challengers, the remaining patent term, the strength of the asserted claims, and the economics of a first-filer launch.

How strong is the Lonsurf patent estate?

The patent estate is moderately durable rather than impenetrable.

Its strengths include:

• A defined active-ingredient combination.
• Multiple clinical indications.
• Strong clinical evidence for colorectal cancer combination use.
• Potential layers of composition, formulation, dosing, and method-of-use protection.
• A commercial product with established physician adoption.

Its weaknesses include:

• Small-molecule generic substitutability.
• The age of the original 2015 approval.
• Dependence on narrower later-use claims as foundational protection expires.
• Potential label-carve-out strategies.
• A late-line market where payers may quickly adopt lower-cost alternatives.

The strongest commercial protection is likely to come from the combination indication and physician adherence to the SUNLIGHT-supported treatment sequence. The weakest protection is likely to be monotherapy after the expiration or successful challenge of core composition patents.

What is the FDA regulatory status of Lonsurf?

Lonsurf is fully approved in the United States for metastatic colorectal cancer and metastatic gastric or gastroesophageal junction adenocarcinoma after prior therapy. The FDA approved the Lonsurf-bevacizumab combination in 2023 based on SUNLIGHT results.[1]

The product carries clinically important warnings for severe myelosuppression. FDA labeling requires blood-count monitoring and dose modification. These requirements affect treatment persistence, supportive-care use, and total cost of therapy.[1]

What licensing deals support Lonsurf commercialization?

Taiho retains the underlying product rights and has used regional commercialization arrangements. Servier has commercial rights for Lonsurf in a number of markets outside the United States and Japan. The arrangement gives Taiho access to Servier’s European and international oncology infrastructure while allowing Taiho to retain a direct U.S. and Japanese presence.

The partnership supports geographic reach but divides reported revenue across companies. Taiho’s reported product sales and Servier’s regional revenue should not be added without eliminating intercompany and territory differences.

What is the geographic coverage for Lonsurf?

Lonsurf is marketed across major oncology markets, including the United States, Japan, and European markets. Regulatory timing and reimbursement vary by country.

The United States is strategically important because:

• It has high oncology drug prices.
• Combination therapy can generate greater treatment value.
• The FDA label directly supports broad commercial messaging.
• The market has an established generic litigation pathway.

Japan is important because Taiho has a direct commercial position and strong oncology infrastructure. Europe provides broad geographic coverage through Servier but is more fragmented because health technology assessment, pricing, and reimbursement are country-specific.

Key Takeaways

• Lonsurf’s growth has entered a combination-led phase following the 2023 FDA approval with bevacizumab.
• SUNLIGHT is the central commercial evidence base for colorectal cancer expansion.
• The product has meaningful revenue durability but remains a late-line therapy with a finite patient pool.
• Lonsurf is exposed to small-molecule generic competition, not biosimilar competition.
• Core patent protection reaches the late 2020s, with later-use and formulation claims potentially extending selected protection into the early 2030s.
• The key generic strategies are Paragraph IV challenges, label carve-outs, and settlement-based launches.
• Bevacizumab biosimilars may reduce combination-treatment cost and support Lonsurf uptake.
• Competitive pressure comes primarily from regorafenib, fruquintinib, and future trifluridine/tipiracil generics.
• The most valuable remaining commercial protection is the colorectal cancer combination indication and its associated clinical positioning.

FAQs

When did the FDA approve Lonsurf with bevacizumab?

The FDA approved Lonsurf with bevacizumab on August 2, 2023, for previously treated metastatic colorectal cancer.

Does Lonsurf have orphan-drug protection?

Lonsurf’s regulatory protection depends on the specific indication and FDA designation. Orphan-drug exclusivity, where applicable, is separate from patent protection and does not automatically block every competing product.

Can a generic launch Lonsurf for only colorectal cancer?

Yes. A generic applicant may pursue a label carve-out that omits patented uses, subject to FDA requirements and the scope of the approved generic labeling.

Does bevacizumab biosimilar competition threaten Lonsurf?

Biosimilar bevacizumab competition does not replace Lonsurf, but it can lower the cost of the combination regimen and potentially increase its use.

What is the largest long-term risk to Lonsurf revenue?

The largest long-term risk is accelerated generic entry after a successful Paragraph IV challenge, patent expiration, or settlement-based launch, followed by rapid payer-driven substitution.

References

1. U.S. Food and Drug Administration. (2023). FDA approves trifluridine/tipiracil with bevacizumab for metastatic colorectal cancer. https://www.fda.gov
2. Tabernero, J., et al. (2023). Trifluridine-tipiracil plus bevacizumab for third-line treatment of refractory metastatic colorectal cancer. New England Journal of Medicine, 388, 1657-1667.
3. Shitara, K., et al. (2018). Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer. New England Journal of Medicine, 378, 1407-1418.
4. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.accessdata.fda.gov/scripts/cder/ob/
5. U.S. Food and Drug Administration. (n.d.). Abbreviated new drug application submissions: Patent certifications and Paragraph IV challenges. https://www.fda.gov
6. Taiho Pharmaceutical Co., Ltd. (2024). Corporate and financial information. https://www.taiho.co.jp
7. Servier. (2024). Annual report and financial information. https://www.servier.com

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