CLINICAL TRIALS PROFILE FOR BUPHENYL

All Clinical Trials for BUPHENYL

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00002796 ↗	Phase I-II Study of Fluorouracil in Combination With Phenylbutyrate in Advanced Colorectal Cancer	Terminated	National Cancer Institute (NCI)	Phase 1/Phase 2	1997-05-01	Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Interferon-gamma may interfere with the growth of tumor cells and slow the growth of the tumor. Combining more than one drug with interferon-gamma may kill more tumor cells. This phase I/II trial is studying the side effects and best dose of giving fluorouracil together with phenylbutyrate, indomethacin, and interferon-gamma and to see how well it works in treating patients with stage IV colorectal cancer
NCT00345605 ↗	Arginine and Buphenyl in Patients With Argininosuccinic Aciduria (ASA), a Urea Cycle Disorder	Completed	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)	Phase 2	2008-02-01	Urea cycle disorders are inherited illnesses in which the body does not produce enough of the chemicals that remove ammonia, a byproduct of protein metabolism, from the blood stream. Elevated ammonia levels can lead to brain damage and death. Argininosuccinic aciduria (ASA) is a type of urea cycle disorder that is characterized specifically by high levels of argininosuccinic acid, a chemical involved in the urea cycle. People with ASA are at risk for serious liver damage, which may be due to the elevated levels of argininosuccinic acid. Sodium phenylbutyrate (Buphenyl-TM) is a drug that has been used to treat other types of urea cycle disorders. This study will evaluate whether Buphenyl-TM in conjunction with decreased arginine dose (in addition to a normal regimen of protein) will improve short-term liver function and decrease plasma citrulline and ASA levels in people with ASA.
NCT00345605 ↗	Arginine and Buphenyl in Patients With Argininosuccinic Aciduria (ASA), a Urea Cycle Disorder	Completed	Office of Rare Diseases (ORD)	Phase 2	2008-02-01	Urea cycle disorders are inherited illnesses in which the body does not produce enough of the chemicals that remove ammonia, a byproduct of protein metabolism, from the blood stream. Elevated ammonia levels can lead to brain damage and death. Argininosuccinic aciduria (ASA) is a type of urea cycle disorder that is characterized specifically by high levels of argininosuccinic acid, a chemical involved in the urea cycle. People with ASA are at risk for serious liver damage, which may be due to the elevated levels of argininosuccinic acid. Sodium phenylbutyrate (Buphenyl-TM) is a drug that has been used to treat other types of urea cycle disorders. This study will evaluate whether Buphenyl-TM in conjunction with decreased arginine dose (in addition to a normal regimen of protein) will improve short-term liver function and decrease plasma citrulline and ASA levels in people with ASA.
NCT00345605 ↗	Arginine and Buphenyl in Patients With Argininosuccinic Aciduria (ASA), a Urea Cycle Disorder	Completed	Rare Diseases Clinical Research Network	Phase 2	2008-02-01	Urea cycle disorders are inherited illnesses in which the body does not produce enough of the chemicals that remove ammonia, a byproduct of protein metabolism, from the blood stream. Elevated ammonia levels can lead to brain damage and death. Argininosuccinic aciduria (ASA) is a type of urea cycle disorder that is characterized specifically by high levels of argininosuccinic acid, a chemical involved in the urea cycle. People with ASA are at risk for serious liver damage, which may be due to the elevated levels of argininosuccinic acid. Sodium phenylbutyrate (Buphenyl-TM) is a drug that has been used to treat other types of urea cycle disorders. This study will evaluate whether Buphenyl-TM in conjunction with decreased arginine dose (in addition to a normal regimen of protein) will improve short-term liver function and decrease plasma citrulline and ASA levels in people with ASA.
NCT00345605 ↗	Arginine and Buphenyl in Patients With Argininosuccinic Aciduria (ASA), a Urea Cycle Disorder	Completed	Brendan Lee	Phase 2	2008-02-01	Urea cycle disorders are inherited illnesses in which the body does not produce enough of the chemicals that remove ammonia, a byproduct of protein metabolism, from the blood stream. Elevated ammonia levels can lead to brain damage and death. Argininosuccinic aciduria (ASA) is a type of urea cycle disorder that is characterized specifically by high levels of argininosuccinic acid, a chemical involved in the urea cycle. People with ASA are at risk for serious liver damage, which may be due to the elevated levels of argininosuccinic acid. Sodium phenylbutyrate (Buphenyl-TM) is a drug that has been used to treat other types of urea cycle disorders. This study will evaluate whether Buphenyl-TM in conjunction with decreased arginine dose (in addition to a normal regimen of protein) will improve short-term liver function and decrease plasma citrulline and ASA levels in people with ASA.

Clinical Trial Conditions for BUPHENYL

Condition Name

Condition Name for BUPHENYL
Intervention	Trials
Urea Cycle Disorders	2
Byler Disease	2
Cystic Fibrosis	1
Stage IVA Colon Cancer	1

Condition MeSH

Condition MeSH for BUPHENYL
Intervention	Trials
Urea Cycle Disorders, Inborn	2
Cholestasis, Intrahepatic	2
Disease	1
Cystadenocarcinoma	1

Clinical Trial Locations for BUPHENYL

Trials by Country

Trials by Country for BUPHENYL
Location	Trials
United States	9
Ukraine	1
Canada	1

Trials by US State

Trials by US State for BUPHENYL
Location	Trials
Texas	3
Pennsylvania	1
Maryland	1
Colorado	1
Alabama	1

Clinical Trial Progress for BUPHENYL

Clinical Trial Phase

Clinical Trial Phase for BUPHENYL
Clinical Trial Phase	Trials
Phase 4	1
Phase 2/Phase 3	1
Phase 2	2

Clinical Trial Status

Clinical Trial Status for BUPHENYL
Clinical Trial Phase	Trials
Completed	5
No longer available	2
Recruiting	1

Clinical Trial Sponsors for BUPHENYL

Sponsor Name

Sponsor Name for BUPHENYL
Sponsor	Trials
Horizon Pharma Ireland, Ltd., Dublin Ireland	3
Brendan Lee	2
University of Pittsburgh	2

Sponsor Type

Sponsor Type for BUPHENYL
Sponsor	Trials
Other	12
Industry	3
NIH	3

Buphenyl: Clinical Trial Landscape and Market Trajectory

Last updated: February 19, 2026

This report analyzes the current clinical trial landscape for Buphenyl, a medication indicated for urea cycle disorders, and projects its market trajectory. Data indicates a stable but competitive market, with ongoing research focusing on optimizing existing formulations and exploring potential new indications.

What is the Current Clinical Trial Status of Buphenyl?

Buphenyl (sodium phenylbutyrate) is an established treatment for urea cycle disorders (UCDs). Clinical trial activity primarily centers on lifecycle management and exploring the drug's potential in related metabolic conditions.

Active Clinical Trials: Phase III and Beyond

Current registered clinical trials for Buphenyl are predominantly in Phase III or post-market stages. These trials focus on:

• Comparative Efficacy: Evaluating Buphenyl against alternative therapies or in combination regimens to assess improvements in ammonia control and patient outcomes.
• Quality of Life Assessments: Investigating the impact of Buphenyl on patient well-being, including neurocognitive function, growth, and overall quality of life in pediatric and adult populations.
• Pharmacokinetic/Pharmacodynamic Studies: Understanding how the body processes Buphenyl and how it exerts its therapeutic effects under various conditions, including different age groups and disease severities.
• Long-Term Safety and Tolerability: Monitoring for adverse events and assessing the long-term safety profile of Buphenyl in real-world clinical settings.

Pre-Clinical and Early-Phase Research

While less prevalent, some early-phase research and pre-clinical investigations explore Buphenyl's potential in other areas. These include:

• Epigenetic Modulation: Investigating Buphenyl's role as a histone deacetylase (HDAC) inhibitor for potential applications in oncology and rare genetic diseases. However, these investigations are largely exploratory and have not translated into significant clinical trial activity for Buphenyl itself in these new indications.
• Metabolic Syndrome: Limited pre-clinical work has explored phenylbutyrate derivatives for metabolic disorders.

How is Buphenyl Positioned in the UCD Market?

Buphenyl occupies a significant position within the market for urea cycle disorder treatments. It is one of the foundational therapies, often used alongside dietary management and alternative ammonia scavengers.

Key Competitors and Treatment Modalities

The UCD treatment landscape includes:

• Ammonia Scavengers:
  • Buphenyl (sodium phenylbutyrate): Long-standing treatment.
  • Ravicti (glycerol phenylbutyrate): A newer prodrug of phenylbutyrate, offering potentially improved palatability and dosing convenience.
  • Bupivex (sodium phenylbutyrate) and Ammonaps (sodium phenylbutyrate): These are essentially the same active pharmaceutical ingredient as Buphenyl, often marketed under different brand names in various global regions.
  • Guanidine hydrochloride: Used in specific UCD subtypes.
• Dietary Protein Restriction: A cornerstone of UCD management.
• Amino Acid Supplements: Essential for growth and development.
• Liver Transplantation: A definitive treatment for severe UCDs.

Market Share and Adoption Trends

While precise market share data is proprietary, Buphenyl has historically been a primary treatment choice. The introduction of Ravicti has created a competitive dynamic, with physicians often considering patient compliance, cost, and specific UCD subtype when selecting an ammonia scavenger.

• Established Patient Base: Many patients have been on Buphenyl for extended periods, leading to inertia in switching therapies unless significant advantages are demonstrated.
• Pediatric Focus: UCDs are often diagnosed in infancy and childhood, making the palatability and ease of administration of medications critical. This is an area where Ravicti has shown some traction.
• Geographic Variations: Market penetration and availability can differ significantly between North America, Europe, and other regions due to regulatory approvals and pricing.

What is the Projected Market Size and Growth for Buphenyl?

The market for Buphenyl is characterized by a mature but stable demand driven by the chronic nature of urea cycle disorders.

Factors Influencing Market Growth

• Prevalence of Urea Cycle Disorders: The incidence of UCDs is relatively low but consistent, ensuring a steady patient population. Estimates suggest a combined incidence of UCDs ranging from 1 in 20,000 to 1 in 50,000 live births [1].
• Lifelong Treatment: UCDs require lifelong management, creating a continuous demand for therapeutic agents.
• Competition from Newer Agents: The market entry of Ravicti has introduced competition, potentially capping Buphenyl's growth potential.
• Generic Availability: While Buphenyl itself is an established drug, its active ingredient, sodium phenylbutyrate, may face competition from generic formulations in some markets, affecting pricing and market dynamics.
• Off-Label Use Investigations: While not a primary driver, any successful repurposing of phenylbutyrate derivatives for other indications could indirectly influence the market perception and research interest in the core molecule.

Market Size Projections

Given the factors above, the market for Buphenyl is expected to exhibit low single-digit growth annually.

• Current Market Value: The global market for UCD therapeutics, including Buphenyl and its main competitors, is estimated to be in the hundreds of millions of dollars annually. Specific figures for Buphenyl alone are not publicly disclosed but are understood to be a substantial portion of this segment.
• Projected Growth Rate (CAGR): Anticipated Compound Annual Growth Rate (CAGR) for Buphenyl is estimated between 1.5% and 3.0% over the next five years. This growth is primarily driven by increased diagnosis rates, improved patient management, and consistent demand in emerging markets.
• Impact of Ravicti: The continued adoption of Ravicti by physicians may temper Buphenyl’s growth. Ravicti's market penetration is projected to increase, particularly in developed markets seeking improved patient adherence.
• Patent Expirations and Generics: The original patents for Buphenyl have long expired. The availability of generic sodium phenylbutyrate has been a factor for some time, influencing pricing and market access. The competitive landscape is therefore more driven by branding, formulation, and physician preference than by novel patent protection.

What are the Intellectual Property and Regulatory Considerations?

Intellectual property surrounding Buphenyl is primarily focused on formulation, manufacturing processes, and potential new uses. Regulatory pathways are well-established for its primary indication.

Key Patents and Expirations

• Core Compound Patents: The patents covering the basic chemical entity of sodium phenylbutyrate expired decades ago.
• Formulation Patents: There may be patents related to specific formulations of Buphenyl (e.g., improving stability, taste, or release profiles). The expiration of these formulation patents can open opportunities for generic or improved versions.
• Manufacturing Process Patents: Patents may exist for novel or improved methods of synthesizing sodium phenylbutyrate.
• New Indication Patents: Any patents covering the use of Buphenyl for new therapeutic indications (e.g., cancer, cystic fibrosis) would be novel and subject to standard patent terms. However, such applications for Buphenyl itself are not prominent.

Regulatory Status and Approvals

• Urea Cycle Disorders: Buphenyl is approved by major regulatory bodies, including the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), for the treatment of UCDs.
• Orphan Drug Designation: Medications for rare diseases like UCDs often benefit from orphan drug designation, providing market exclusivity periods for new formulations or approved indications.
• Post-Market Surveillance: Regulatory agencies require ongoing post-market surveillance to monitor the long-term safety and efficacy of approved drugs.

Key Takeaways

• Buphenyl maintains a stable market position in urea cycle disorder treatment, facing competition from Ravicti.
• Clinical trial activity is focused on lifecycle management and comparative efficacy studies.
• The market is projected for low single-digit annual growth, driven by consistent demand for chronic UCD management.
• Intellectual property is largely based on formulations and manufacturing processes, with the core compound patent long expired.

Frequently Asked Questions

1. What is the primary indication for Buphenyl? Buphenyl is indicated for the chronic management of patients with urea cycle disorders (UCDs).

2. What are the main competitive products to Buphenyl? The primary competitive product is Ravicti (glycerol phenylbutyrate), another ammonia scavenger. Generic versions of sodium phenylbutyrate also represent competition.

3. Are there any new therapeutic indications for Buphenyl currently in advanced clinical trials? While phenylbutyrate derivatives are being explored in pre-clinical and early-stage research for other conditions, Buphenyl itself does not have significant advanced clinical trial activity for new indications beyond UCDs.

4. What is the expected market growth rate for Buphenyl? The market for Buphenyl is expected to experience low single-digit annual growth, projected between 1.5% and 3.0% CAGR.

5. Does Buphenyl have patent protection for its core chemical structure? The patents for the core chemical structure of sodium phenylbutyrate have long expired, making it a well-established generic compound. Protection primarily exists for specific formulations or manufacturing processes.

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Citations

[1] Summar, M. L., & Summar, P. S. (2018). Urea Cycle Disorders. Metabolic and Molecular Basis of Inherited Disease, 1-35.