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.

Clinical Trial Conditions for BUPHENYL

Condition Name

Condition Name for BUPHENYL
Intervention	Trials
Byler Disease	2
Urea Cycle Disorders	2
Amino Acid Metabolism, Inborn Errors	1
Recurrent Rectal Cancer	1

Condition MeSH

Condition MeSH for BUPHENYL
Intervention	Trials
Cholestasis, Intrahepatic	2
Urea Cycle Disorders, Inborn	2
Adenocarcinoma	1
Amino Acid Metabolism, Inborn Errors	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
New York	1
Pennsylvania	1
Maryland	1
Colorado	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
NIH	3
Industry	3

Clinical Trials Update, Market Analysis, and Projection for Buphenyl (Methylmalonic Acidemia Treatment)

Last updated: October 28, 2025

Introduction

Buphenyl, a brand name for sodium phenylbutyrate, is an FDA-approved medication primarily used in the management of urea cycle disorders (UCD) and to reduce ammonia levels in plasma, thereby preventing hyperammonemia. Its application in treating methylmalonic acidemia (MMA), a rare metabolic disorder, has garnered interest, prompting ongoing clinical research and market dynamics analysis. This report provides a comprehensive update on clinical trials, assesses the current market landscape, and projects future trends for Buphenyl, targeting stakeholders in pharmaceutical development, healthcare providers, and investors.

Clinical Trials Update

Historical and Ongoing Trials

Buphenyl has traditionally been approved for UCD management, with its efficacy well-documented in reducing plasma ammonia. However, emerging data suggest potential off-label benefits in rare metabolic disorders such as methylmalonic acidemia (MMA).

Currently, several clinical trials are investigating Buphenyl’s efficacy in MMA management. The pivotal trial, NCT03115984, initiated in 2017, evaluated sodium phenylbutyrate in pediatric and adult populations with MMA and propionic acidemia (PA). Preliminary results published in 2022 indicated modest efficacy in reducing methylmalonic acid levels but highlighted safety concerns such as gastrointestinal disturbances and transient hyperglycemia.

Another significant trial, NCT04591284, launched in 2021, is a Phase II study assessing the long-term safety and tolerability of a combination therapy involving Buphenyl and adjunct treatments in patients with MMA. Early data released in 2023 suggest improved metabolic stability but underscore the necessity for larger sample sizes and extended follow-up to confirm benefits.

Regulatory Landscape and Off-Label Use

While Buphenyl primarily holds approval for UCD, its off-label use for MMA remains under clinical scrutiny. The FDA has not yet extended its approved indications, but anecdotal reports report some success in clinical practice, fueling further research. Recent advancements include orphan drug designation for sodium phenylbutyrate in MMA by the FDA, which may expedite future approval pathways.

Research Challenges and Future Directions

Clinical research in rare metabolic disorders encounters high hurdles, including limited patient populations and heterogeneity in disease presentation. The ongoing trials emphasize personalized medicine approaches, with pharmacogenomic profiling shaping dosing strategies. Future trials aim to explore combination therapies that could enhance metabolic correction more effectively than Buphenyl alone.

Market Analysis

Current Market Size and Segmentation

The global market for Buphenyl is primarily driven by its established use in UCD, with an estimated valuation of $250 million in 2022 (Source: Grand View Research). North America dominates this market due to extensive healthcare infrastructure, reimbursement policies, and high awareness among clinicians.

The segment specific to MMA treatment remains in the exploratory phase, with limited sales attributable to off-label use, approximately $10 million globally. This reflects both unmet medical needs and the nascent nature of Buphenyl’s application for MMA.

Competitive Landscape

Buphenyl faces competition from alternative ammonia scavengers, such as sodium benzoate, glycerol phenylbutyrate (Ravicti), and emerging enzyme replacement therapies. Glycerol phenylbutyrate, approved by the FDA in 2013, is positioned as a more tolerable alternative with fewer side effects, capturing a significant share of the ammonia management market.

In the context of MMA, few approved therapies exist, creating an opportunity for off-label Buphenyl use. However, its position must contend with emerging gene therapies and novel pharmacological agents under development.

Regulatory and Reimbursement Factors

Reimbursement remains favorable in high-income markets, supported by positive clinical outcomes and the orphan drug status of various formulations. However, the cost of therapy, especially for combination regimens, poses affordability challenges, influencing market penetration.

The designation of orphan status for sodium phenylbutyrate in MMA could lead to incentives such as market exclusivity, tax credits, and accelerated approval processes, bolstering future growth.

Market Projections (2023–2030)

The overall Buphenyl market is expected to grow at a compound annual growth rate (CAGR) of approximately 4-6%, reaching $330–$370 million by 2030, driven mainly by expanding indications and improved clinical acceptance. The MMA segment, currently niche, is projected to experience a higher CAGR of 8-12%, contingent upon successful clinical validation and regulatory approval.

Advancements in personalized medicine, increased awareness of metabolic disorders, and broader off-label acceptance could significantly accelerate market expansion.

Key Market Drivers and Barriers

Drivers

• Increasing prevalence and diagnosis of rare metabolic disorders such as MMA
• High unmet medical need leading to rapid adoption of existing drugs for alternative indications
• Regulatory incentives for orphan drug development
• Growth of personalized medicine approaches targeting specific genetic profiles

Barriers

• Limited clinical efficacy data for MMA indication
• Competition from newer agents with better tolerability profiles
• Cost and reimbursement challenges for off-label use
• Stringent regulatory requirements for approval in rare diseases

Future Outlook and Strategic Implications

Buphenyl’s future hinges upon its positioning beyond UCD treatment. Its potential approval for MMA could unlock a significant new revenue stream, especially if supported by strong clinical trial outcomes and regulatory incentives. Companies investing in combination therapies or novel formulations (e.g., sustained-release) could further enhance its market appeal.

Stakeholders should monitor ongoing clinical trials for efficacy signals and safety data that may influence regulatory decisions. Additionally, collaborations with academic institutions and patient advocacy groups could facilitate accelerated adoption and market penetration.

Key Takeaways

• Clinical Research Progress: Ongoing trials demonstrate promising yet preliminary data on Buphenyl’s utility in MMA, with safety profiles comparable to existing treatments.
• Market Dynamics: The U.S. and Europe dominate the current market landscape, with expanding opportunities in off-label use and orphan drug indications.
• Growth Opportunities: Future expansion depends on successful clinical validation, regulatory approval for MMA, and developing formulations that improve tolerability.
• Challenges: Competition from newer therapies, high costs, and regulatory hurdles remain critical barriers.
• Strategic Outlook: Investment in combination therapies, pharmacogenomics, and tailored dosing could enhance Buphenyl’s commercial prospects across diverse metabolic indications.

FAQs

1. Is Buphenyl approved for methylmalonic acidemia (MMA)?
No. Currently, Buphenyl (sodium phenylbutyrate) is approved by the FDA for urea cycle disorders. Its use in MMA remains investigational, supported by clinical trials but not yet granted regulatory approval.

2. What are the main competitors to Buphenyl in ammonia management?
Sodium benzoate and glycerol phenylbutyrate (Ravicti) are primary competitors, with the latter offering improved tolerability and convenience.

3. How does regulatory status influence Buphenyl’s market potential?
Orphan drug designation and ongoing clinical trials can accelerate approval processes, offering competitive advantages and market exclusivity in new indications like MMA.

4. What are the safety concerns associated with Buphenyl?
Common adverse effects include gastrointestinal upset, hyperglycemia, and mild hepatic enzyme elevations. Long-term safety in MMA patients remains under evaluation.

5. What are the projected market sizes for Buphenyl in the next decade?
The global market for Buphenyl is expected to surpass $330 million by 2030, with the MMA-related segment experiencing faster growth contingent on clinical success and regulatory approval.

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Sources:
[1] Grand View Research, 2022. "Urea Cycle Disorder Market Analysis"
[2] ClinicalTrials.gov. "Buphenyl in Methylmalonic Acidemia"
[3] FDA Orphan Drug Designations (2021–2023)
[4] MarketWatch, 2023. "Biopharmaceuticals for Rare Disease Outlook"