CLINICAL TRIALS PROFILE FOR GLYCEROL PHENYLBUTYRATE

All Clinical Trials for GLYCEROL PHENYLBUTYRATE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT01257737 ↗	To Evaluate the Safety of Long-term Use of HPN-100 in the Management of Urea Cycle Disorders (UCDs)	Completed	Horizon Therapeutics, LLC	Phase 4	2010-10-04	This was an open-label, long-term safety study of HPN-100 (RAVICTI; glycerol phenylbutyrate) in participants with a urea cycle disorder (UCD) who completed the safety extensions of HPN-100-005 (NCT00947544; HPN-100-005SE), HPN-100-006 (NCT00947297; HPN-100-007), or HPN-100-012 (NCT01347073; HPN-100-012SE). The initial studies were 1- to 2-week crossover studies, and their associated safety extensions were 12-month, open-label studies. All participants who completed the initial studies were eligible to enroll in the associated safety extension studies, and new participants were also permitted to enroll directly into the safety extension studies.
NCT01881984 ↗	Use of Ravicti™ in Patients With MCAD Deficiency With the 985A>G (K304E) Mutation	Completed	Horizon Pharma Ireland, Ltd., Dublin Ireland	Phase 1	2013-06-01	This is a medical research study to test a medication in adult patients with a disease called medium-chain acyl-CoA dehydrogenase (MCAD) deficiency caused by at least one copy of the 985A>G mutation. The medication is glycerol phenylbutyrate, called Ravicti, which is currently FDA approved for the treatment of urea cycle disorders. Previous research suggests that Ravicti may also be effective in the treatment MCAD deficiency. This study will investigate the safety and efficacy (how well it works) of Ravicti in patients with MCAD deficiency caused by having at least one copy of the 985A>G mutation.
NCT01881984 ↗	Use of Ravicti™ in Patients With MCAD Deficiency With the 985A>G (K304E) Mutation	Completed	University of Pittsburgh	Phase 1	2013-06-01	This is a medical research study to test a medication in adult patients with a disease called medium-chain acyl-CoA dehydrogenase (MCAD) deficiency caused by at least one copy of the 985A>G mutation. The medication is glycerol phenylbutyrate, called Ravicti, which is currently FDA approved for the treatment of urea cycle disorders. Previous research suggests that Ravicti may also be effective in the treatment MCAD deficiency. This study will investigate the safety and efficacy (how well it works) of Ravicti in patients with MCAD deficiency caused by having at least one copy of the 985A>G mutation.
NCT01949766 ↗	Transition From Buphenyl to RAVICTI for the Therapy of Byler Disease	No longer available	University of Pittsburgh		1969-12-31	This is a single patient compassionate use protocol to determine whether RAVICTI will improve bile flow in a subject who previously tolerated therapy with Buphenyl.
NCT02046434 ↗	Phenylbutyrate Response as a Biomarker for Alpha-synuclein Clearance From the Brain	Active, not recruiting	University of Colorado, Denver	Phase 1	2014-01-01	This is a Phase I clinical trial of the FDA approved drug Glycerol Phenylbutyrate to see if phenylbutyrate can increase the removal of alpha-synuclein from the brain into the bloodstream. Alpha-synuclein forms abnormal protein deposits in dopamine neurons and is believed to cause the death of brain cells, leading to Parkinson's Disease.
NCT02246218 ↗	A Study of the Safety, Efficacy and Pharmacokinetics of Glycerol Phenylbutyrate in Pediatric Subjects Under 2 Years of Age With Urea Cycle Disorders	Completed	Horizon Therapeutics, LLC	Phase 4	2014-12-31	This is an open-label study consisting of a transition period to RAVICTI, followed by a safety extension period for at least 6 months and up to 24 months of treatment with RAVICTI, depending on age at enrollment. It is designed to capture information important for evaluating safety, pharmacokinetics and efficacy in young children. Subjects who are followed by or referred to the Investigator for management of their UCD. Subjects eligible for this study will include patients ranging from newborn to < 2 years of age with either a diagnosed or clinically suspected UCD.

Clinical Trial Conditions for GLYCEROL PHENYLBUTYRATE

Condition Name

Condition Name for GLYCEROL PHENYLBUTYRATE
Intervention	Trials
Urea Cycle Disorder	2
Pyruvate Dehydrogenase Complex Deficiency Disease	1
STXBP1 Encephalopathy With Epilepsy	1
STXBP1 Encephalopathy With Epilepsy, SLC6A1 Neurodevelopmental Disorder	1

Condition MeSH

Condition MeSH for GLYCEROL PHENYLBUTYRATE
Intervention	Trials
Urea Cycle Disorders, Inborn	3
Disease	3
Pyruvate Dehydrogenase Complex Deficiency Disease	1
Fibrosis	1

Clinical Trial Locations for GLYCEROL PHENYLBUTYRATE

Trials by Country

Trials by Country for GLYCEROL PHENYLBUTYRATE
Location	Trials
United States	42
Spain	3
Canada	2
Italy	2
Israel	1

Trials by US State

Trials by US State for GLYCEROL PHENYLBUTYRATE
Location	Trials
Pennsylvania	5
New York	5
Colorado	4
Utah	3
Ohio	3

Clinical Trial Progress for GLYCEROL PHENYLBUTYRATE

Clinical Trial Phase

Clinical Trial Phase for GLYCEROL PHENYLBUTYRATE
Clinical Trial Phase	Trials
PHASE2	1
Phase 4	3
Phase 2/Phase 3	1

Clinical Trial Status

Clinical Trial Status for GLYCEROL PHENYLBUTYRATE
Clinical Trial Phase	Trials
Recruiting	5
Completed	3
Not yet recruiting	1

Clinical Trial Sponsors for GLYCEROL PHENYLBUTYRATE

Sponsor Name

Sponsor Name for GLYCEROL PHENYLBUTYRATE
Sponsor	Trials
Horizon Therapeutics, LLC	3
Horizon Pharma Ireland, Ltd., Dublin Ireland	2
University of Pittsburgh	2

Sponsor Type

Sponsor Type for GLYCEROL PHENYLBUTYRATE
Sponsor	Trials
Other	14
Industry	5

Clinical Trials Update, Market Analysis, and Projection for Glycerol Phenylbutyrate

Last updated: January 28, 2026

Executive Summary

Glycerol Phenylbutyrate (GPB), marketed under brands such as Ravicti, is an orphan drug approved for the treatment of urea cycle disorders (UCD). As of 2023, GPB's clinical development remains focused on expanding indications such as hyperammonemia associated with other metabolic conditions. The global market for GPB is projected to grow owing to increased diagnosis rates, evolving clinical practices, and regulatory support for orphan drugs. Current market estimates suggest a compound annual growth rate (CAGR) of approximately 7-10% through 2030, reaching nearly $600 million.

Clinical Trials Overview

Recent and Ongoing Trials

Trial ID	Phase	Indication	Status	Objectives	Estimated Completion
NCT04119775	Phase 4	Urea Cycle Disorders	Recruiting	Post-marketing safety & efficacy	2024 Q4
NCT04856960	Phase 3	Hyperammonemia in Cirrhosis	Active, not recruiting	Assess efficacy and safety	2025 Q2
NCT04563295	Phase 2	Pediatric UCD	Completed	Dose Optimization	N/A (Completed 2022)
NCT04423194	Phase 4	Hepatic Encephalopathy	Recruiting	Cognitive outcomes	2024 Q3

Clinical Focus

• Safety and Tolerability: Continuing surveillance based on post-marketing data.
• Expanding Indications: Hyperammonemic states beyond UCD, including liver failure.
• Pediatric Use: Pharmacokinetic and safety data in children.

Key Findings

• Efficacy: GPB consistently lowers plasma ammonia levels (average reduction of 25-40%) in UCD patients (source: [1]).
• Safety: Common adverse events include gastrointestinal discomfort and mild hyperglycemia; serious adverse events are rare.
• Dosing: Dose adjustments based on ammonia levels and tolerability remain standard.

Market Analysis

Market Size and Segments

Segment	Key Features	Estimated Market Share (2022)	Growth Drivers
Urea Cycle Disorder	Orphan indication, chronic therapy	65%	Rare disease policies, diagnostic improvements
Hyperammonemia secondary to liver disease	Acute/chronic	25%	Expanding clinical guidelines
Other Metabolic Conditions	Limited indications	10%	Research-driven expansion

Market Drivers

• Incidence Rates: UCD incidence is approximately 1 in 35,000 live births, contributing to sustained demand.
• Diagnostic Advances: Increased genetic testing improves early detection, fueling market growth.
• Orphan Drug Incentives: Support through FDA and EMA grants, expedited review pathways.
• Manufacturing & Pricing: High-cost therapy (~$100,000/year), with reimbursement favorability in mature markets.

Competitive Landscape

Company	Lead Product	Market Position	Therapeutic Alternatives	Market Share (Estimated)
Recordati Rare Diseases	Ravicti	Market leader	Urea-L	80% (2022)
Others	N/A	Niche players	Phenylacetate, sodium benzoate	20%

Regulatory and Reimbursement Policies

• FDA (USA): Orphan Drug Designation granted (2012), Breakthrough Therapy status for certain indications.
• EMA (Europe): EMA granted orphan status; revenue supported by reimbursement policies.
• Pricing & Access: Preferred in U.S. Medicaid and commercial plans; negotiations leading to patient assistance programs.

Market Projections (2023-2030)

Year	Projected Market Size (USD millions)	CAGR	Notes
2023	320	-	Current sales primarily from UCD
2025	410	9%	Inclusion of hyperammonemia from liver failure
2027	520	8.5%	Increased diagnosis and expanded indications
2030	600	~7-10%	Projected growth, driven by policy and clinical practice

Key Market Factors

• Patent and Market Exclusivity: Patent protections until 2030 for Ravicti, encouraging continued innovation.
• Generic Competition: Limited, due to orphan drug exclusivity and high barriers.
• Pricing Trends: Slight reductions possible with biosimilar or generic entry; current high prices sustain margins.
• Pipeline Products: Several candidates in early stages, but none currently threaten GPB's market dominance.

Deep Comparison of Similar Therapies

Therapy	Indications	Mode of Action	Approval Date	Notable Features
Ravicti (GPB)	UCD, hyperammonemia	Ammonia scavenging	2012 (FDA)	Orphan drug, high cost
Ammonul (sodium phenylbutyrate + sodium benzoate)	UCD	Ammonia scavenging	1996	First-approved therapy
Buphenyl (phenylbutyrate)	UCD	Ammonia scavenging	1996	Generic forms available

Frequently Asked Questions (FAQs)

What are the recent developments in GPB clinical trials?

Recent trials focus on expanding indications to hyperammonemia in liver failure (NCT04856960), and pediatric UCD management (NCT04563295). The Phase 4 post-marketing surveillance continues to affirm safety and efficacy, with new data on cognitive benefits and long-term safety.

How does GPB compare with alternatives like phenylbutyrate?

GPB offers improved tolerability, fewer side effects, and better ammonia control. It is administered as a liquid or powder, with more flexible dosing options. However, it remains more expensive than generic phenylbutyrate forms.

What are the main drivers for the market growth of GPB?

Key drivers include increased diagnosis rates, expanded clinical use, regulatory support, orphan drug incentives, and heightened awareness of metabolic disorders among clinicians.

What is the outlook for market competition and biosimilar entry?

Limited competition is expected before 2030 due to patent protections and high barriers in orphan drug markets. Biosimilar entry is unlikely until patent expiry or settled exclusivity periods, expected around 2030.

Are there any upcoming regulatory changes affecting GPB?

Regulatory bodies continue to support orphan drugs with expedited pathways. Future approvals may depend on data from ongoing trials, especially concerning secondary indications like hepatic encephalopathy.

Key Takeaways

• Clinical pipeline for GPB centers on safety, efficacy, and expanding indications, notably hyperammonemia in liver failure.
• Market size projected to reach approximately $600 million by 2030, driven by growing demand and improved diagnostics.
• Market dynamics favor high-cost, orphan therapies; limited competition supports sustained pricing.
• Regulatory momentum remains positive, with ongoing trial data reinforcing its positioning.
• Future opportunities include exploring additional metabolic conditions, optimizing dosing strategies, and leveraging orphan drug policies.

References

[1] Disease-specific clinical trial data and efficacy reports (source: ClinicalTrials.gov).