Thymidine Phosphorylase Inhibitor Drug Class List

Drugs in Drug Class: Thymidine Phosphorylase Inhibitor

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	9,943,537
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	207981-002	Sep 22, 2015	AB	RX	Yes	Yes	9,527,833		Y	Y
Taiho Oncology	LONSURF	tipiracil hydrochloride; trifluridine	TABLET;ORAL	207981-001	Sep 22, 2015	AB	RX	Yes	No	9,527,833		Y	Y

Market Dynamics and Patent Landscape of Thymidine Phosphorylase Inhibitors in Oncology

The global market for thymidine phosphorylase inhibitors (TPIs) is witnessing transformative growth driven by advances in targeted cancer therapies and expanding clinical applications. With a projected compound annual growth rate (CAGR) of 7.73% from 2023 to 2031[1], this drug class is poised to address unmet needs in metastatic colorectal, gastric, and esophageal cancers. Concurrently, the patent landscape reflects intense innovation and strategic litigation, underscoring the therapeutic and commercial significance of TPIs.

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Therapeutic Applications and Market Segmentation

Metastatic Colorectal Cancer Dominates Clinical Use

Metastatic colorectal cancer (mCRC) accounts for the largest share of TPI applications, supported by robust clinical validation of drugs like Lonsurf® (trifluridine/tipiracil). This combination therapy inhibits thymidine phosphorylase (TP) to prevent degradation of trifluridine, enhancing its bioavailability and antineoplastic efficacy[2][8]. The U.S. Food and Drug Administration (FDA) has approved Lonsurf® for mCRC patients who have exhausted fluoropyrimidine-, oxaliplatin-, and irinotecan-based regimens[2][6]. Its adoption is further bolstered by compatibility with bevacizumab, extending progression-free survival in refractory cases[8].

Emerging Applications in Gastric and Esophageal Cancers

TPIs are gaining traction in gastric and gastroesophageal junction cancers, particularly in Asia-Pacific markets where incidence rates are elevated[1]. Clinical trials demonstrate that Lonsurf® improves outcomes in patients pretreated with taxanes or HER2-targeted therapies[2]. Additionally, preclinical studies highlight TPIs' angiostatic properties, which suppress tumor vascularization in esophageal squamous cell carcinoma models[3][13].

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Market Drivers and Competitive Landscape

Rising Cancer Burden and Demand for Targeted Therapies

Global cancer prevalence, fueled by aging populations and lifestyle factors, has amplified the need for therapies with reduced off-target toxicity. TPIs exemplify this shift, as they selectively disrupt DNA synthesis in rapidly dividing cancer cells while sparing healthy tissues[1][9]. This mechanistic precision aligns with trends toward personalized oncology, driving pharmaceutical investment in TPIs.

Strategic Positioning of Key Players

Taiho Pharmaceutical Co., Ltd. dominates the TPI market through its flagship product Lonsurf®, protected by a dense patent portfolio. Patent RE46284 covers the oral administration of trifluridine and tipiracil at a 1:0.5 molar ratio, with dosage regimens optimized for five-day cycles[2][6]. Competitors like Les Laboratoires Servier and Elevar Therapeutics are advancing next-generation TPIs, though Taiho’s first-mover advantage and extensive litigation defenses (e.g., against Eugia, Natco) reinforce its market leadership[6][8].

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Patent Landscape and Litigation Dynamics

Core Patents and Exclusivity Strategies

Taiho’s RE46284 and US7799783B2 patents are pivotal, claiming methods for co-administering trifluridine with TPIs to enhance pharmacokinetics[4][8]. These patents, expiring between 2023 and 2031, face challenges from generic manufacturers seeking to launch biosimilars. For instance, Natco Pharma Ltd. secured FDA approval for a generic TAS-102 formulation in 2023, prompting Taiho to litigate under Hatch-Waxman provisions[6][8].

Innovation in Drug Delivery and Combination Therapies

Recent patents emphasize synergistic combinations, such as TPIs with histone deacetylase (HDAC) inhibitors or radiation therapy. Shuttle Pharmaceuticals, for example, holds U.S. Patent 11,654,157 for using TPIs to sensitize tumors to radiotherapy, potentially expanding their utility into glioblastoma and other radioresistant cancers[5]. Such innovations aim to circumvent existing IP barriers while addressing clinical resistance mechanisms.

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Emerging Trends in TPI Development

Non-Competitive Inhibition and Reduced Toxicity

Next-gen TPIs like compound 8g (IC₅₀ = 0.48 µM) exhibit non-competitive inhibition, preventing substrate-driven resistance[3]. Unlike first-gen analogs, these derivatives show negligible cytotoxicity in healthy fibroblasts, reducing risks of anemia and neutropenia[13]. Molecular docking studies reveal allosteric binding to TP’s active site, a mechanism leveraged in dihydropyrimidone derivatives now entering Phase I trials[13].

Repurposing TPIs for Non-Oncologic Indications

Preclinical data suggest TPIs mitigate thrombotic events by inhibiting platelet-derived TP, which regulates Lyn kinase signaling in clot formation[14]. Tipiracil hydrochloride reduced arterial thrombosis in murine models without increasing bleeding risk, positioning TPIs as potential alternatives to conventional antiplatelets like clopidogrel[14].

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Regional Market Analysis

North America: High Adoption Amidst Patent Expirations

North America leads in revenue share (45–50%), attributed to premium pricing of Lonsurf® ($12,000–$15,000 per treatment cycle) and robust insurance coverage[1][8]. However, biosimilar encroachment post-2025 may pressure margins, incentivizing innovation in biomarker-driven TPIs.

Asia-Pacific: Fastest-Growing Region

With a CAGR exceeding 9%, Asia-Pacific’s growth is propelled by rising gastric cancer incidence and government initiatives to accelerate oncology drug approvals[1][11]. Chia Tai Tianqing Pharmaceutical is advancing oral TPIs tailored to Asian pharmacogenomic profiles, aiming to capture 20–25% of the regional market by 2030[1].

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Challenges and Future Outlook

Toxicity and Compliance Barriers

Despite targeted mechanisms, TPIs carry risks of myelosuppression and gastrointestinal toxicity, necessitating dose optimization[9][10]. Ongoing trials explore intermittent dosing and prophylactic granulocyte colony-stimulating factor (G-CSF) to improve tolerability[6][8].

Generic Competition and Market Saturation

The impending loss of exclusivity for Lonsurf® patents will likely fragment the TPI market, with generics capturing 30–40% of revenue by 2031[1][8]. Taiho’s pipeline, including TPIs conjugated with antibody-drug conjugates (ADCs), aims to counter this through differentiated products[5].

Regulatory and Clinical Opportunities

FDA Fast Track designations for novel TPIs (e.g., SYD-101, LTG-001) signal regulatory support for expanded indications[7]. Concurrently, biomarker-driven trials targeting TP-overexpressing tumors could enhance patient stratification, reducing trial attrition rates[3][13].

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Strategic Recommendations for Stakeholders

1. Monitor Patent Litigations: Anticipate biosimilar entry timelines by tracking ongoing Hatch-Waxman cases[6][8].
2. Invest in Non-Competitive Inhibitors: Prioritize TPIs with non-reversible kinetics to outpace generics[3][13].
3. Explore Combination Regimens: Leverage TPIs’ angiostatic and immunomodulatory effects in cocktail therapies[5][14].
4. Target Emerging Markets: Capitalize on Asia-Pacific’s growth via localized manufacturing and pricing strategies[1][11].

In summary, the TPI market is navigating a critical juncture, balancing patent cliffs against scientific breakthroughs. Stakeholders adopting proactive IP and R&D strategies will likely dominate this evolving therapeutic frontier.

References

1. https://www.growthplusreports.com/report/thymidine-phosphorylase-inhibitors-market/8826
2. https://www.drugpatentwatch.com/p/patent/RE46284
3. https://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.8b01305
4. https://patents.google.com/patent/US7799783B2/en
5. https://shuttlepharma.com/wp-content/uploads/2024/03/Shuttle-Pharma-Investor-Presentation-February-2024.pdf
6. https://www.govinfo.gov/content/pkg/USCOURTS-ded-1_19-cv-02321/pdf/USCOURTS-ded-1_19-cv-02321-0.pdf
7. https://www.empr.com/news/march-2025-recap-drug-pipeline-updates/
8. https://www.drugpatentwatch.com/p/tradename/lonsurf
9. https://www.rxlist.com/thymidine_phosphorylase_inhibitors/drug-class.htm
10. https://www.oaepublish.com/articles/cdr.2021.21
11. https://www.jstage.jst.go.jp/article/cbij/17/0/17_19/_pdf
12. https://xtalks.com/top-30-pharma-and-biotech-companies-in-2023-statistics-and-trends-3482/
13. https://pmc.ncbi.nlm.nih.gov/articles/PMC10143232/
14. https://www.ahajournals.org/doi/10.1161/ATVBAHA.120.315109