CLINICAL TRIALS PROFILE FOR TRIFLURIDINE

All Clinical Trials for Trifluridine

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00000138 ↗	Herpetic Eye Disease Study (HEDS) I	Unknown status	National Eye Institute (NEI)	Phase 3	1989-05-01	To evaluate the efficacy of topical corticosteroids in treating herpes simplex stromal keratitis in conjunction with topical trifluridine. To evaluate the efficacy of oral acyclovir in treating herpes simplex stromal keratitis in patients receiving concomitant topical corticosteroids and trifluridine. To evaluate the efficacy of oral acyclovir in treating herpes simplex iridocyclitis in conjunction with treatment with topical corticosteroids and trifluridine.
NCT00000635 ↗	Treatment of Acyclovir-Resistant Mucocutaneous Herpes Simplex Disease in Patients With AIDS: Open Label Pilot Study of Topical Trifluridine	Completed	Glaxo Wellcome	N/A	1969-12-31	To determine the safety, effectiveness, and toxicity of topical (local) trifluridine in treating mucocutaneous (at the nasal, oral, vaginal, and anal openings) Herpes simplex virus ( HSV ) disease that has shown resistance to acyclovir in HIV-infected patients. HSV infection in patients with AIDS is often associated with skin sores and frequent recurrences. Treatment with the drug acyclovir results in healing for most patients, but repeated treatment sometimes results in resistance of the virus to acyclovir. Thus, when this happens, other treatments need to be used. Trifluridine is an antiviral drug that is used for the treatment of Herpes infections that occur in the eye. This study attempts to determine if trifluridine is useful for treating HSV sores that have not healed after treatment with acyclovir.
NCT00000635 ↗	Treatment of Acyclovir-Resistant Mucocutaneous Herpes Simplex Disease in Patients With AIDS: Open Label Pilot Study of Topical Trifluridine	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	N/A	1969-12-31	To determine the safety, effectiveness, and toxicity of topical (local) trifluridine in treating mucocutaneous (at the nasal, oral, vaginal, and anal openings) Herpes simplex virus ( HSV ) disease that has shown resistance to acyclovir in HIV-infected patients. HSV infection in patients with AIDS is often associated with skin sores and frequent recurrences. Treatment with the drug acyclovir results in healing for most patients, but repeated treatment sometimes results in resistance of the virus to acyclovir. Thus, when this happens, other treatments need to be used. Trifluridine is an antiviral drug that is used for the treatment of Herpes infections that occur in the eye. This study attempts to determine if trifluridine is useful for treating HSV sores that have not healed after treatment with acyclovir.
NCT00002037 ↗	Evaluation of the Therapeutic Benefit of r-metHuIFN- Gamma in AIDS Patients With Disseminated Mycobacterium Avium-Intracellulare (MAI) Infection: A Multi-Centered Pilot Study	Completed	Amgen	N/A	1969-12-31	To examine the effectiveness of subcutaneous gamma interferon in reducing severity of Mycobacterium avium- intracellulare (MAI) bacillemia episodes in AIDS patients in an open-label dose-randomized multi-center pilot clinical investigation. To evaluate the safety of gamma interferon given by subcutaneous injection (SC) in the AIDS patient in the presence and absence of AZT therapy.
NCT00081835 ↗	Evaluation and Treatment of Eye Complications of Vaccinia Vaccination	Completed	National Eye Institute (NEI)	Phase 2	2004-04-19	This study will evaluate patients with eye complications related to vaccination against smallpox to learn more about these conditions. Vaccinia vaccination has been used for more than 100 years for preventing smallpox. A small number of people who receive the vaccination (less than 1 in 1,000) develop complications, sometimes in their eyes. This usually results from the accidental transfer of the infection from the vaccination site to the face or eyes, perhaps by touching the vaccination area and then the face or eyelids before washing the hands. The study will also examine whether an experimental treatment called NP-016 vaccinia immune globulin can reduce corneal scarring that is sometimes associated with serious vaccinia complications and can impair vision. Children and adults with keratitis, severe conjunctivitis, or blepharitis following exposure to vaccinia vaccination may be eligible for this study. Children must weigh at least 10 kg. Participants undergo the following tests and procedures at enrollment, with some tests repeated at scheduled study visits: 1. Medical history and physical examination 2. Infectious disease consultation 3. Complete eye evaluation including: - Fundus photography to examine the back of the eye - dilation of the pupils with eye drops to examine and photograph the back of the eye - Slit lamp biomicroscopy - evaluation of the front part of the eye with a slit lamp microscope - Eye pressure measurements - Eye swab to look for vaccinia virus or other causes of disease 4. Blood tests 5. Photographs and documentation of eye and skin lesions 6. Vaccinia diagnostic tests, such as skin or mucosa scrapings; blood, throat, or urine cultures; and tissue biopsies, if needed Patients begin treatment with standard medications for their eye disease, such as trifluridine (Viroptic® (Registered Trademark)) anti-viral eye drops. Patients whose condition becomes serious are offered additional treatment with intravenous (through a vein) infusions of either VIG or placebo (salt water solution with no active drug) and are randomly assigned to one or the other treatment group. All patients continue standard-of-care treatment as well. Follow-up visits at the NIH eye clinic are scheduled as required by the patient's condition. Patients with mild complications who are taking only standard medications may need to be seen only 1 month after the initial visit and then 6 months and 12 months later. Patients with more serious conditions who qualify for VIG or placebo treatments may be seen daily for a week, then once a week for the rest of the first month, and then at 6 months and 12 months, unless more frequent treatment or observation is required.
NCT01867866 ↗	Study Comparing the Pharmacokinetics of FTD as a Component of TAS-102 With FTD Alone	Completed	Taiho Oncology, Inc.	Phase 1	2013-05-01	The purpose of this study is to compare the pharmacokinetics of trifluorothymidine (FTD) as a component of TAS-102 with FTD alone.

Clinical Trial Conditions for Trifluridine

Condition Name

Condition Name for Trifluridine
Intervention	Trials
Metastatic Colorectal Cancer	12
Colorectal Cancer	9
Stage IVC Colorectal Cancer AJCC v8	6
Stage IV Colorectal Cancer AJCC v8	6

Condition MeSH

Condition MeSH for Trifluridine
Intervention	Trials
Colorectal Neoplasms	41
Adenocarcinoma	17
Carcinoma	9
Colonic Neoplasms	8

Clinical Trial Locations for Trifluridine

Trials by Country

Trials by Country for Trifluridine
Location	Trials
United States	122
Italy	28
China	25
Japan	18
Australia	11

Trials by US State

Trials by US State for Trifluridine
Location	Trials
California	11
Texas	10
Florida	8
Minnesota	8
Arizona	8

Clinical Trial Progress for Trifluridine

Clinical Trial Phase

Clinical Trial Phase for Trifluridine
Clinical Trial Phase	Trials
Phase 3	12
Phase 2	36
Phase 1/Phase 2	6

Clinical Trial Status

Clinical Trial Status for Trifluridine
Clinical Trial Phase	Trials
Recruiting	29
Not yet recruiting	15
Completed	7

Clinical Trial Sponsors for Trifluridine

Sponsor Name

Sponsor Name for Trifluridine
Sponsor	Trials
National Cancer Institute (NCI)	14
Taiho Oncology, Inc.	5
Mayo Clinic	4

Sponsor Type

Sponsor Type for Trifluridine
Sponsor	Trials
Other	59
Industry	34
NIH	17

Trifluridine: Clinical Trials, Market Analysis, and Projections

Introduction to Trifluridine

Trifluridine, often combined with tipiracil and marketed as Lonsurf, is a nucleoside analog that has gained significant attention in the treatment of various cancers and other medical conditions. Here, we will delve into recent clinical trials, market analysis, and projections for this drug.

Clinical Trials Update

Trifluridine/Tipiracil in Biliary Tract Cancer

A recent phase II trial investigated the safety and efficacy of trifluridine/tipiracil in combination with irinotecan for patients with advanced, refractory biliary tract carcinoma (BTC). The trial enrolled 28 patients who had progressed on at least one prior systemic therapy. The primary endpoint was the 16-week progression-free survival (PFS16) rate, which was met with a 37% success rate. The median PFS and overall survival (OS) were 3.9 months and 9.1 months, respectively. While the combination showed promise, it was associated with significant adverse events, including grade 3 or worse events in 74.1% of patients[1].

Trifluridine/Tipiracil Plus Bevacizumab in Colorectal Cancer

The SUNLIGHT trial, a phase 3 study, evaluated the combination of trifluridine/tipiracil with bevacizumab in patients with previously treated metastatic colorectal cancer (mCRC). The trial demonstrated that the combination therapy significantly improved overall survival and progression-free survival compared to trifluridine/tipiracil alone. Patients receiving the combination therapy had a median OS of 10.8 months and a median PFS of 5.6 months, compared to 7.5 months and 2.4 months, respectively, for those receiving trifluridine/tipiracil alone. This study set a new standard for the treatment of metastatic colorectal cancers that have stopped responding to other treatments[4].

Mechanism of Action

Trifluridine causes DNA damage that can lead to the death of cancer cells. Tipiracil, when combined with trifluridine, helps maintain blood concentrations of trifluridine by inhibiting an enzyme that degrades it. Bevacizumab, when added to this combination, blocks the activity of VEGF, a protein that helps tumors grow new blood vessels, thereby starving the tumors of oxygen and nutrients[4].

Market Analysis

Current Market Size and Forecast

The global market for trifluridine was estimated to be worth US$ 25 million in 2023 and is forecasted to grow to US$ 46 million by 2030, with a compound annual growth rate (CAGR) of 7.9% during the forecast period of 2024-2030. This growth is driven by increasing demand for effective cancer treatments and the expanding application spectrum of trifluridine[2].

Key Players

The trifluridine market is dominated by several key players, including Biophore, Taiho Pharmaceutical, Natco Pharma, Yuki Gosei Kogyo, Lusochimica, and Shanghai Haoyuan Chemexpress. These companies are driving innovation and expansion in the market through various strategies such as product development, strategic partnerships, and geographical expansion[2].

Market Drivers

• Growing Prevalence of Cancer: The increasing incidence of cancers such as colorectal and gastric cancer is driving the demand for trifluridine.
• Advancements in Drug Formulations: Innovations in drug formulations and the development of combination therapies are enhancing the efficacy and broadening the application spectrum of trifluridine.
• Expansion of Healthcare Infrastructure: The growth of healthcare infrastructure in emerging economies is improving access to cancer therapeutics, including trifluridine[5].

Market Restraints

• Regulatory Approvals: Stringent regulatory approvals and potential side effects associated with long-term use can limit the growth of the trifluridine market.
• Economic Hurdles: Economic factors affecting the affordability and accessibility of trifluridine medications are significant challenges.
• Clinical Trial Setbacks: Delays and setbacks in clinical trials can slow the pace of market advancements[5].

Market Opportunities

• Personalized Medicine: There is a growing opportunity for trifluridine in personalized medicine applications, particularly in precision oncology care.
• Nucleoside Analogs in Oncology: Trifluridine is positioned to be a key player in the growing field of nucleoside analogs in oncology.
• Pediatric Cancer Applications: Evaluating opportunities for pediatric cancer applications of trifluridine in regulatory and R&D pipelines presents a potential area of growth[5].

Cost-Effectiveness and Pharmacoeconomic Analysis

The combination of trifluridine/tipiracil with bevacizumab has been evaluated for its cost-effectiveness. According to the CADTH clinical review, this combination may be associated with prolonged OS and PFS but at a higher cost. The incremental cost-effectiveness ratio (ICER) was estimated to be $195,000 per quality-adjusted life-year (QALY) gained compared to best supportive care (BSC). This indicates that while the combination is effective, it is not considered cost-effective at current prices[3].

Side Effects and Safety Profile

Clinical trials have highlighted that the combination of trifluridine/tipiracil with other drugs, such as irinotecan or bevacizumab, is associated with significant adverse events. Common side effects include neutropenia, nausea, anemia, and hypertension. Despite these side effects, most patients have been reported to tolerate the agents reasonably well[1][4].

Key Takeaways

• Clinical Efficacy: Trifluridine/tipiracil combinations have shown promising results in clinical trials for various cancers, including biliary tract cancer and metastatic colorectal cancer.
• Market Growth: The global market for trifluridine is expected to grow significantly, driven by increasing demand for cancer treatments and advancements in drug formulations.
• Cost-Effectiveness: While the combination therapies involving trifluridine are effective, they are associated with high costs and may not be considered cost-effective at current prices.
• Safety Profile: The treatment is associated with significant adverse events, but most patients tolerate the agents reasonably well.

FAQs

What is the current market size of trifluridine, and what is the forecasted growth?

The global market for trifluridine was estimated to be worth US$ 25 million in 2023 and is forecasted to grow to US$ 46 million by 2030, with a CAGR of 7.9% during the forecast period of 2024-2030[2].

Which companies are the main players in the trifluridine market?

The main players in the trifluridine market include Biophore, Taiho Pharmaceutical, Natco Pharma, Yuki Gosei Kogyo, Lusochimica, and Shanghai Haoyuan Chemexpress[2].

What are the common side effects associated with trifluridine/tipiracil combination therapies?

Common side effects include neutropenia, nausea, anemia, and hypertension, particularly when combined with bevacizumab[1][4].

Is the combination of trifluridine/tipiracil with bevacizumab considered cost-effective?

The combination is not considered cost-effective at current prices, with an ICER of $195,000 per QALY gained compared to best supportive care (BSC)[3].

What are the potential market opportunities for trifluridine in the future?

Potential opportunities include personalized medicine applications, positioning in the growing field of nucleoside analogs in oncology, and evaluating pediatric cancer applications[5].

Sources

1. Phase II Trial of Trifluridine/Tipiracil Plus Irinotecan in Patients with Refractory, Advanced Unresectable Biliary Tract Carcinoma. PubMed.
2. Trifluridine - Market, Report Size, Worth, Revenue, Growth, Industry. Valuates Reports.
3. Pharmacoeconomic Review - Trifluridine-Tipiracil (Lonsurf). NCBI.
4. Avastin and Lonsurf for Advanced Colorectal Cancer. National Cancer Institute.
5. Trifluridine Market Size & Share 2025-2030. 360iResearch.