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.

This drug has one hundred and twenty-three patent family members in thirty-four countries.

The generic ingredient in LONSURF is tipiracil hydrochloride; trifluridine. There are two drug master file entries 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

International Patents:	123
US Patents:	6
Applicants:	1
NDAs:	1
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for LONSURF

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	RE46284
Taiho Oncology	LONSURF	tipiracil hydrochloride; trifluridine	TABLET;ORAL	207981-001	Sep 22, 2015	AB	RX	Yes	No	10,456,399
Taiho Oncology	LONSURF	tipiracil hydrochloride; trifluridine	TABLET;ORAL	207981-002	Sep 22, 2015	AB	RX	Yes	Yes	RE46284
Taiho Oncology	LONSURF	tipiracil hydrochloride; trifluridine	TABLET;ORAL	207981-002	Sep 22, 2015	AB	RX	Yes	Yes	10,457,666		Y	Y
Taiho Oncology	LONSURF	tipiracil hydrochloride; trifluridine	TABLET;ORAL	207981-001	Sep 22, 2015	AB	RX	Yes	No	9,943,537

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
Taiwan	201534601	Stabilized crystal of tipiracil hydrochloride, and crystallization method for same
Lithuania	1849470
European Patent Office	1080726	AGENTS ATTENUANT LES EFFETS SECONDAIRES (AGENTS FOR RELIEVING SIDE EFFECTS)
Russian Federation	2727598	СПОСОБ ЛЕЧЕНИЯ БОЛЬНЫХ РАКОМ С ТЯЖЕЛОЙ ПОЧЕЧНОЙ НЕДОСТАТОЧНОСТЬЮ (METHOD OF TREATING PATIENTS WITH CANCER WITH SEVERE RENAL INSUFFICIENCY)
Denmark	1080726

Supplementary Protection Certificates for LONSURF

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
1849470	17C1028	France		PRODUCT NAME: TRIFLURIDINE/TIPIRACIL; REGISTRATION 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	C 2017 032	Romania		PRODUCT NAME: TRIFLURIDINA IN COMBINATIE CU TIPIRACIL SAU O SARE ACCEPTABILA FARMACEUTIC DE TIPIRACIL CUM AR FI CLORHIDRAT DE TIPIRACIL; NATIONAL AUTHORISATION NUMBER: EU/1/16/1096; DATE OF NATIONAL AUTHORISATION: 20160425; NUMBER OF FIRST AUTHORISATION IN EUROPEAN ECONOMIC AREA (EEA): EU/1/16/1096; DATE OF FIRST AUTHORISATION IN EEA: 20160425
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
1849470	PA2017024	Lithuania		PRODUCT NAME: TRIFLURIDINAS/TIPIRACILAS; REGISTRATION NO/DATE: EU/1/16/1096 20160425

LONSURF (Trifluridine/Tipiracil) — Investment Scenario and Fundamentals Analysis

Last updated: April 23, 2026

What is LONSURF and how is it used commercially?

LONSURF (trifluridine/tipiracil, TAS-102) is an oral combination therapy used in oncology, primarily for colorectal cancer. It is marketed for:

• Metastatic colorectal cancer that has progressed after standard therapies, and
• Previously treated metastatic colorectal cancer, consistent with major label frameworks used by regulators and payers (pricing and coverage vary by jurisdiction).

The investment relevance is straightforward: LONSURF’s revenue base is driven by (1) remaining-line penetration in colorectal cancer, (2) durability of patient treatment cycles, and (3) competitive access versus fluoropyrimidine alternatives, biologics, and later-line standards.

How does the product’s evidence shape prescribing and pricing power?

LONSURF’s clinical foundation is built on randomized data supporting survival benefit in refractory metastatic colorectal cancer settings. The product is widely treated as a later-line backbone option where options narrow after progression on standard regimens. This matters for fundamentals because late-line drugs typically:

• Show less prescriber switching once a patient is in a later-line pathway,
• Face coverage gating based on line-of-therapy and molecular stratification, and
• Are sensitive to new late-line entrants that can displace current standards.

What does the competitive landscape look like for late-line colorectal cancer?

For an investment view, the key issue is displacement risk: drugs that enter later lines with superior outcomes or stronger tolerability profiles can reduce LONSURF addressable volume.

Core competitive forces by mechanism and practical care pathway:

1. Other cytotoxic and oral fluoropyrimidine variants used in later lines
2. Targeted therapies in biomarker-defined populations (when applicable)
3. Immunotherapy and combinations for MSI-high or TMB-high subsets
4. Device and regimen shifts (sequence changes) that change the “time-on-LONSURF” window

The market outcome depends on whether competitors expand the eligible population into lines where LONSURF already competes or force earlier switches away from LONSURF.

What is the product economics profile investors should model?

LONSURF’s fundamentals are typically modelled using a reimbursement-and-volume framework common to oncology portfolios:

• Net price (list price adjusted for rebates, discounts, and payer terms)
• Channel mix (US commercial vs. international markets)
• Patient starts (new treatment initiations per period)
• Duration per treated patient (cycle length and discontinuation rates)
• Share of eligible late-line patients (competitive win-rate by regimen sequence)

Given the oral dosing format and established later-line positioning, investors usually assume revenue is less dependent on infusion site infrastructure and more dependent on:

• formulary positioning,
• prior authorization behavior,
• toxicity management that impacts adherence.

What are the key patent and exclusivity signals affecting downside and upside?

From a fundamentals standpoint, the valuation risk is driven by:

• Patent expiry timing, and
• Exclusivity protections that delay generic erosion.

LONSURF’s patent estate must be assessed by geography (US, EU5, UK, Japan) with attention to:

• compound coverage,
• method-of-use claims,
• formulation claims,
• patent term adjustments and regulatory exclusivity.

Because generic competition impacts net price sharply for oral oncology products, investors usually tie terminal value sensitivity to the earliest realistic generic entry date and likely penetration curve.

What are the regulatory and label factors that shape long-term demand?

Label scope drives accessible patient pool. For LONSURF, demand is tied to colorectal cancer line-of-therapy language used by payers and clinicians. The investment implication:

• A stable label supports forecast stability.
• Narrow or later-line-only label language increases sensitivity to guideline changes and competitor entrants that can absorb later-line usage.

The product’s historical adoption has largely depended on refractory colorectal cancer treatment pathways rather than first-line expansion, which constrains TAM but supports durability when late-line standards remain stable.

What pipeline and lifecycle actions determine the next valuation step?

Lifecycle value for established oncology assets comes from two buckets:

• Line expansion or broader label through new trials
• Combination strategy that improves response and reduces discontinuation

For LONSURF, investment-grade screening should focus on whether clinical development supports any of the following:

1. Meaningful efficacy improvement in settings where it is currently used
2. Acceptable safety/tolerability that improves adherence and treatment duration
3. Companion regimen adoption into guideline-based pathways

Combination trials that produce practice-changing results can extend the revenue period by converting LONSURF from a single-agent “last option” to part of a broader regimen ecosystem.

How should investors assess R&D and manufacturing execution risk?

For oral oncology products, operational risk is usually less about manufacturing capacity and more about:

• maintaining stable supply under demand volatility,
• managing batch release and quality control over time,
• minimizing treatment disruption that harms adherence and reimbursement compliance.

Execution matters because oncology payers often monitor outcomes and may tighten utilization if real-world adherence declines.

What are the key fundamentals risks specific to LONSURF?

Investment-grade downside typically comes from:

• Guideline displacement in later-line metastatic colorectal cancer
• Trial-driven competitive substitution that reduces eligible starts
• Formulary deterioration due to price pressure or value reassessments
• Patent or exclusivity erosion that accelerates generic adoption
• Safety and tolerability that reduces treatment duration (affects prescription volume and persistence)

What are the key upside levers?

Upside generally comes from:

• Improved competitive positioning through better efficacy, convenience, or safety data
• New label lines or stronger evidence enabling broader sequencing
• Favorable payer negotiation outcomes that expand formularies
• Combination regimens that increase average treated duration or improve sequencing share

Investment scenario framework

A practical scenario model for LONSURF should be built around three drivers: volume, price, and duration.

Base case (steady late-line demand)

Assumptions investors typically use:

• Late-line colorectal standards remain stable.
• LONSURF retains formulary coverage and payer access.
• Competitive pressure gradually reduces share, but does not drive abrupt displacement.
• Treatment duration and discontinuation rates remain within historical ranges.

Downside case (rapid displacement or faster access loss)

Assumptions:

• A competitor gains guideline adoption for a similar patient pool.
• Payers tighten utilization management (more step therapy, prior authorization, restricted formularies).
• Net price declines faster than expected via negotiation or increased rebate pressure.
• Discontinuation rises due to safety profile comparisons or competing alternatives with better tolerability.

Upside case (combination or sequencing advantage)

Assumptions:

• Combination or sequencing trials support broader uptake.
• Treatment duration improves due to reduced toxicity or better management protocols.
• Payer access expands through improved outcomes or contract renegotiation.
• Competitive entrants capture less share than expected.

Comparative considerations investors should use across oncology portfolios

When benchmarking LONSURF against other established oncology franchises, investors should compare:

• Degree of line-of-therapy constraint (how narrow the eligible population is)
• Depth of competitive substitution (how easily clinicians switch)
• Timing to generic exposure (patent and exclusivity)
• Real-world persistence (treatment duration and adherence)

LONSURF typically scores as a later-line asset with meaningful persistence sensitivity and strong dependency on reimbursement access.

Key Takeaways

• LONSURF’s fundamentals are driven by late-line metastatic colorectal cancer demand, payer access, and persistence (treatment duration).
• Investment upside is anchored in label expansion or regimen adoption that increases starts and/or extends duration.
• Investment downside is anchored in guideline displacement, net price compression, and generic erosion risk tied to patent/exclusivity timing by geography.
• A scenario model should treat volume, net price, and duration as separate levers rather than a single revenue growth rate.

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FAQs

1) What cancer setting is LONSURF primarily tied to?

LONSURF is primarily used for colorectal cancer in later-line settings after progression on standard therapies. Label specifics and coverage vary by region and payer policy.

2) What matters most for revenue stability in LONSURF?

Formulary access (including prior authorization and reimbursement rules), the number of eligible late-line patients, and treatment persistence.

3) How does competition typically affect LONSURF?

Competition usually reduces LONSURF share by substituting into the same late-line sequencing slot, and by tightening payer utilization management as alternative options gain coverage.

4) What are the biggest generic-entry risks to monitor?

The earliest realistic generic entry dates across key markets, driven by patent expiry and regulatory exclusivity constraints.

5) What development outcomes would be most financially material?

Any evidence that expands use beyond current lines or improves outcomes enough to change sequencing and payer coverage.

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References (APA)

[1] U.S. Food and Drug Administration. (n.d.). Lonsurf (trifluridine and tipiracil) prescribing information and label information. FDA. https://www.fda.gov/