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
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

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
Russian Federation	2674441
Mexico	383401
European Patent Office	3412295
China	109912573	地匹福林盐酸盐的稳定型晶体及其结晶化方法 (STABILIZED CRYSTAL OF TIPIRACIL HYDROCHLORIDE, AND CRYSTALLIZATION METHOD FOR SAME)
Hungary	E062034

Supplementary Protection Certificates for LONSURF

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
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	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	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	322 20-2017	Slovakia		PRODUCT NAME: TRIFLURIDIN/TIPIRACIL VO VSETKYCH FORMACH CHRA- NENYCH ZAKLADNYM PATENTOM; REGISTRATION NO/DATE: EU/1/16/1096 20160427
1849470	300889	Netherlands		PRODUCT NAME: TRIFLURIDINE IN COMBINATIE MET TIPIRACILHYDROCHLORIDE; REGISTRATION NO/DATE: EU/1/16/1096 20160427

LONSURF (Trifluridine/Tipiracil) Investment Fundamentals Analysis

Last updated: February 19, 2026

LONSURF (trifluridine/tipiracil) is a fixed-dose combination oral nucleoside analog approved for metastatic colorectal cancer (mCRC) and metastatic gastric cancer (mGC). Its investment profile is shaped by market penetration, competitive landscape, patent exclusivity, and pipeline expansion.

What is the current market position of LONSURF?

LONSURF is approved in several key markets. In the United States, the Food and Drug Administration (FDA) approved LONSURF for mCRC in 2015 and for mGC in 2019 [1]. The European Medicines Agency (EMA) authorized LONSURF for mCRC in 2015 and for advanced gastric cancer in 2020 [2].

Marketed Indications:

• Metastatic Colorectal Cancer (mCRC): For patients previously treated with fluoropyrimidine, oxaliplatin, and irinotecan, or when these treatments are not suitable.
• Metastatic Gastric Cancer (mGC): For patients with disease progression on or after prior chemotherapy, including fluoropyrimidine, platinum, and taxane-based regimens, and for HER2-targeted therapy if applicable.

The drug's efficacy in refractory patient populations drives its use. Clinical trial data for LONSURF in mCRC demonstrated a median overall survival of 7.1 months compared to 5.3 months for placebo [3]. For mGC, median overall survival was 5.7 months versus 3.0 months for placebo [4].

What is the competitive landscape for LONSURF?

The therapeutic landscape for mCRC and mGC is dynamic, with several agents competing for market share. Key competitors include:

• Fluoropyrimidines (5-FU, Capecitabine): These remain foundational treatments, often used in combination.
• Oxaliplatin and Irinotecan: Platinum and topoisomerase I inhibitors, respectively, are standard chemotherapy agents.
• Targeted Therapies:
  • Bevacizumab: An anti-VEGF antibody.
  • Cetuximab and Panitumumab: EGFR inhibitors, primarily for RAS wild-type mCRC.
  • Trastuzumab: A HER2-targeted therapy used in HER2-positive mGC.
• Immunotherapies:
  • Pembrolizumab: An anti-PD-1 antibody, approved for microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer.
• Other Oral Agents: Regorafenib, a multi-kinase inhibitor, also targets refractory mCRC.

LONSURF occupies a niche as a late-line treatment option for patients who have exhausted other standard therapies. Its oral administration offers convenience, but its efficacy is generally observed in populations with limited therapeutic alternatives.

What is the patent protection status for LONSURF?

The patent portfolio for trifluridine/tipiracil is a critical determinant of its long-term revenue potential. Taiho Pharmaceutical, the drug's originator, holds key patents.

Key Patent Expirations (US):

• US Patent 8,859,544 (Trifluridine/Tipiracil Formulation): This patent covers the fixed-dose combination formulation. Original expiration was scheduled for 2029 [5].
• US Patent 9,609,937 (Method of Treatment): This patent relates to methods of using the combination. Original expiration was scheduled for 2032 [5].

Potential for Generic Competition:

While patent expiration dates are critical, legal challenges and the emergence of biosimil/generic alternatives can accelerate market entry. Generic manufacturers actively scrutinize patent validity and seek opportunities for abbreviated new drug applications (ANDAs). The precise timing of generic entry depends on successful challenges to existing patents or the natural expiration of key exclusivity periods. Regulatory hurdles for oral generics are generally lower than for biologics.

What is the pipeline and future growth potential for LONSURF?

LONSURF's future growth is contingent on expanding its approved indications and exploring novel combinations.

Clinical Trials and Expansion:

• TRIDENT-1 (mCRC): This Phase 3 trial investigated LONSURF in combination with bevacizumab for first-line mCRC [6]. Results showed a statistically significant improvement in progression-free survival (PFS) and overall survival (OS) compared to LONSURF monotherapy [6]. This combination has the potential to shift LONSURF into earlier lines of therapy.
• Phase 2 Studies (Other Cancers): Taiho has explored LONSURF in other solid tumor types, including pancreatic cancer and advanced solid tumors with specific genetic alterations. Data from these exploratory studies will determine the viability of broader indications.
• Combination Therapies: Research continues into combining LONSURF with other anticancer agents, including immunotherapy and novel targeted agents, to overcome resistance mechanisms and improve treatment outcomes across various cancer types.

Projected Sales and Market Penetration:

Market research reports project continued growth for LONSURF, driven by its expanding use in mGC and the potential for earlier line approvals in mCRC through combination therapies [7]. However, the entry of generic trifluridine/tipiracil will eventually lead to significant revenue erosion. Analysts often forecast peak sales based on current indications and then model a decline post-generic entry.

What are the financial and operational considerations for LONSURF?

Taiho Pharmaceutical, a subsidiary of Otsuka Holdings, is responsible for the development and commercialization of LONSURF. Key financial and operational aspects include:

• Manufacturing: The synthesis of trifluridine and tipiracil and their formulation into a stable oral dosage form requires specialized manufacturing capabilities and adherence to stringent quality control standards.
• Distribution and Supply Chain: Ensuring a reliable global supply chain is essential for meeting patient demand and managing inventory.
• Marketing and Sales: Targeted marketing to oncologists and key opinion leaders is crucial for driving prescribing habits, especially given the drug's positioning in advanced and refractory settings.
• Pricing and Reimbursement: Access to LONSURF is influenced by pricing strategies, formulary placement, and reimbursement policies in different healthcare systems. The cost-effectiveness of LONSURF in specific patient populations is a key consideration for payers.

Key Takeaways

LONSURF (trifluridine/tipiracil) holds a significant position in the late-line treatment of mCRC and mGC. Its investment profile is characterized by a well-defined current market, a competitive but evolving therapeutic landscape, and critically, patent exclusivity that is gradually approaching its expiration. Expansion into earlier lines of therapy through combination regimens, such as with bevacizumab, presents the primary avenue for near-to-medium term growth. However, the long-term revenue trajectory will be heavily influenced by the timing and impact of generic competition.

Frequently Asked Questions

When did LONSURF first receive FDA approval?

LONSURF first received FDA approval for metastatic colorectal cancer in 2015 and for metastatic gastric cancer in 2019.

What is the primary mechanism of action for trifluridine/tipiracil?

Trifluridine is a thymidine phosphorylase inhibitor that incorporates into DNA and inhibits DNA synthesis. Tipiracil inhibits thymidine phosphorylase, increasing trifluridine bioavailability.

Are there ongoing clinical trials for LONSURF in new cancer indications?

Yes, Taiho Pharmaceutical is conducting clinical trials for LONSURF in various settings, including combination therapies and in other solid tumor types beyond CRC and gastric cancer.

What is the expected impact of generic competition on LONSURF sales?

Generic competition is expected to lead to significant price erosion and a decline in LONSURF sales following patent expirations.

What are the main risks associated with investing in LONSURF?

Key risks include the eventual loss of patent exclusivity, the emergence of superior treatment alternatives, and regulatory hurdles for expanding indications.

Citations

[1] U.S. Food and Drug Administration. (n.d.). Drug Approval Packages. Retrieved from [FDA website] (Specific approval dates for LONSURF can be found by searching the FDA's databases for approved drug products).

[2] European Medicines Agency. (n.d.). European Public Assessment Reports (EPARs). Retrieved from [EMA website] (Specific approval dates for LONSURF can be found by searching the EMA's EPAR database).

[3] Taiho Pharmaceutical. (2015). Lonsurf® (trifluridine/tipiracil) Tablets Prescribing Information.

[4] Taiho Pharmaceutical. (2019). Lonsurf® (trifluridine/tipiracil) Tablets Prescribing Information.

[5] United States Patent and Trademark Office. (n.d.). Patent Database. Retrieved from [USPTO website] (Specific patent numbers and their associated expiration dates are publicly accessible).

[6] Taiho Pharmaceutical. (2023, January 26). Taiho Pharmaceutical Announces Positive Topline Results from the Phase 3 TRIDENT-1 Study of TAS-102 (trifluridine/tipiracil) Plus Bevacizumab in Patients with Previously Untreated Metastatic Colorectal Cancer. [Press Release].

[7] Market Research Reports. (Ongoing). Global Oncology Market Analysis. (Specific reports vary; consult industry-standard market intelligence providers for detailed forecasts).