GLYCEROL PHENYLBUTYRATE - Generic Drug Details

What are the generic drug sources for glycerol phenylbutyrate and what is the scope of freedom to operate?

Glycerol phenylbutyrate is the generic ingredient in two branded drugs marketed by Ph Health and Horizon Therap Us, and is included in two NDAs. There are fifteen patents protecting this compound and one Paragraph IV challenge. Additional information is available in the individual branded drug profile pages.

Glycerol phenylbutyrate has one hundred and fifteen patent family members in thirty countries.

There are two drug master file entries for glycerol phenylbutyrate. Three suppliers are listed for this compound. There is one tentative approval for this compound.

Summary for GLYCEROL PHENYLBUTYRATE

International Patents:	115
US Patents:	15
Tradenames:	2
Applicants:	2
NDAs:	2
Drug Master File Entries:	2
Finished Product Suppliers / Packagers:	3
Raw Ingredient (Bulk) Api Vendors:	47
Clinical Trials:	12
Patent Applications:	369
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for GLYCEROL PHENYLBUTYRATE
What excipients (inactive ingredients) are in GLYCEROL PHENYLBUTYRATE?	GLYCEROL PHENYLBUTYRATE excipients list
DailyMed Link:	GLYCEROL PHENYLBUTYRATE at DailyMed

Recent Clinical Trials for GLYCEROL PHENYLBUTYRATE

Identify potential brand extensions & 505(b)(2) entrants

Sponsor	Phase
Assistance Publique - Hpitaux de Paris	PHASE2
Technical University of Munich	Phase 2
Columbia University	Early Phase 1

See all GLYCEROL PHENYLBUTYRATE clinical trials

Generic filers with tentative approvals for GLYCEROL PHENYLBUTYRATE

Applicant	Application No.	Strength	Dosage Form
		1.1G/ML	LIQUID;ORAL

The 'tentative' approval signifies that the product meets all FDA standards for marketing, and, but for the patents / regulatory protections, it would approved.

Pharmacology for GLYCEROL PHENYLBUTYRATE

Drug Class	Nitrogen Binding Agent
Mechanism of Action	Ammonium Ion Binding Activity

Medical Subject Heading (MeSH) Categories for GLYCEROL PHENYLBUTYRATE

Cryoprotective Agents

Solvents

Anatomical Therapeutic Chemical (ATC) Classes for GLYCEROL PHENYLBUTYRATE

A06AG	Enemas
A06A	DRUGS FOR CONSTIPATION
A06	DRUGS FOR CONSTIPATION
A	Alimentary tract and metabolism

A06AX	Other drugs for constipation
A06A	DRUGS FOR CONSTIPATION
A06	DRUGS FOR CONSTIPATION
A	Alimentary tract and metabolism

A16AX	Various alimentary tract and metabolism products
A16A	OTHER ALIMENTARY TRACT AND METABOLISM PRODUCTS
A16	OTHER ALIMENTARY TRACT AND METABOLISM PRODUCTS
A	Alimentary tract and metabolism

Paragraph IV (Patent) Challenges for GLYCEROL PHENYLBUTYRATE

Tradename	Dosage	Ingredient	Strength	NDA	ANDAs Submitted	Submissiondate
RAVICTI	Oral Liquid	glycerol phenylbutyrate	1.1 g/mL	203284	1	2013-11-19

US Patents and Regulatory Information for GLYCEROL PHENYLBUTYRATE

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Horizon Therap Us	RAVICTI	glycerol phenylbutyrate	LIQUID;ORAL	203284-001	Feb 1, 2013	AA	RX	Yes	Yes	10,183,005
Horizon Therap Us	RAVICTI	glycerol phenylbutyrate	LIQUID;ORAL	203284-001	Feb 1, 2013	AA	RX	Yes	Yes	10,045,958
Horizon Therap Us	RAVICTI	glycerol phenylbutyrate	LIQUID;ORAL	203284-001	Feb 1, 2013	AA	RX	Yes	Yes	9,326,966

Expired US Patents for GLYCEROL PHENYLBUTYRATE

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	Patent No.	Patent Expiration
Horizon Therap Us	RAVICTI	glycerol phenylbutyrate	LIQUID;ORAL	203284-001	Feb 1, 2013	5,968,979

EU/EMA Drug Approvals for GLYCEROL PHENYLBUTYRATE

Company	Drugname	Inn	Product Number / Indication	Status	Generic	Biosimilar	Orphan	Marketing Authorisation	Marketing Refusal
Immedica Pharma AB	Ravicti	glycerol phenylbutyrate	EMEA/H/C/003822Ravicti is indicated for use as adjunctive therapy for chronic management of patients with urea cycle disorders (UCDs) including deficiencies of carbamoyl phosphate-synthase-I (CPS), ornithine carbamoyltransferase (OTC), argininosuccinate synthetase (ASS), argininosuccinate lyase (ASL), arginase I (ARG) and ornithine translocase deficiency hyperornithinaemia-hyperammonaemia homocitrullinuria syndrome (HHH) who cannot be managed by dietary protein restriction and/or amino acid supplementation alone.Ravicti must be used with dietary protein restriction and, in some cases, dietary supplements (e.g., essential amino acids, arginine, citrulline, protein-free calorie supplements).	Authorised	no	no	yes	2015-11-26

International Patents for GLYCEROL PHENYLBUTYRATE

Country	Patent Number	Title	Estimated Expiration
China	104039358	Methods of therapeutic monitoring of nitrogen scavenging drugs
Mexico	2014012694	METODOS DE MONITOREO TERAPEUTICO DE PROFARMACOS DE ACIDO FENILACETICO. (METHODS OF THERAPEUTIC MONITORING OF PHENYLACETIC ACID PRODRUGS.)
Japan	5577341

Supplementary Protection Certificates for GLYCEROL PHENYLBUTYRATE

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
2330892	PA2016041,C2330892	Lithuania		PRODUCT NAME: GLICEROLIO FENILBUTIRATAS; REGISTRATION NO/DATE: EU/1/15/1062 20151127
2330892	2016C/074	Belgium		PRODUCT NAME: GLYCEROLFENYLBUTYRAAT; AUTHORISATION NUMBER AND DATE: EU/1/15/1062 20151201
2330892	93351	Luxembourg		PRODUCT NAME: GLYCEROL PHENYLBUTYRATE; AUTHORISATION NUMBER AND DATE: EU/1/15/1062

Market Dynamics and Financial Trajectory for Glycerol Phenylbutyrate

Last updated: July 30, 2025

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Introduction

Glycerol phenylbutyrate (GPB) is an innovative prodrug designed to manage urea cycle disorders (UCD), fundamental conditions affecting ammonia detoxification in the liver. Developed as an alternative to existing treatments like sodium phenylbutyrate and sodium benzoate, GPB offers potential advantages in efficacy, tolerability, and patient compliance. As a novel therapeutic agent, the market dynamics surrounding GPB are shaped by regulatory approvals, competitive landscape, healthcare adoption, and evolving diagnostics for UCDs.

This analysis delineates the current and projected market landscape, key financial trajectories, and emerging drivers and challenges influencing GPB's commercial prospects.

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Market Overview

Urea Cycle Disorders and Therapeutic Needs

Urea cycle disorders are rare genetic conditions arising from enzyme deficiencies involved in ammonia detoxification, leading to hyperammonemia. Although rare, the high morbidity and mortality associated with acute hyperammonemic crises underscore the critical demand for effective management solutions [1].

Current standards include ammonia scavengers such as sodium phenylbutyrate and glycerol phenylbutyrate. The latter's favorable pharmacokinetics and tolerability profiles position it as an advantageous alternative, potentially expanding the therapeutic market.

Regulatory Approvals and Market Penetration

Glycerol phenylbutyrate received FDA approval in 2014 under the brand name Ravicti (developed by Hyperion Therapeutics, now part of UCB). Its approval marked a significant milestone, providing a non-invasive, liquid formulation with flexible dosing [2].

In Europe, GPB gained approval in subsequent years, broadening geographical access. The approval process was facilitated by expedited pathways recognizing the treatment’s unmet needs, especially for patients experiencing tolerability issues with older therapies.

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Market Dynamics

Drivers

• Unmet Clinical Needs: The rarity of UCDs limits market size but underscores the necessity for safer, more tolerable treatments. GPB's improved mind state of patients and ease of administration bolsters its adoption among clinicians.

• Regulatory Incentives: Orphan drug designations and orphan drug exclusivity periods incentivize pharmaceutical investment, extending market exclusivity periods and recoupment opportunities.

• Patient Compliance: Liquid formulations like GPB improve compliance, especially in pediatric populations, fostering greater uptake.

• Expanding Diagnostic Capabilities: Advances in genetic screening and newborn screening programs intensify early diagnosis, expanding the diagnosed population pool and, consequently, potential patient base.

Challenges

• High Cost: Orphan drugs typically command premium pricing. The high per-treatment cost can limit reimbursement and patient access, especially in markets with constrained healthcare budgets.

• Competitive Landscape: Sodium phenylbutyrate remains a cost-effective standard therapy. Although GPB demonstrates clinical benefits, competition from older agents and generics threaten market share.

• Limited Patient Population: The ultra-rare nature of UCDs constrains sales volume. Market growth largely depends on increased diagnoses and expanded indications.

• Physician Awareness: Low disease prevalence can impede clinician familiarity, delaying disease identification and therapy initiation.

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Financial Trajectory

Initial Sales and Revenue Estimates

Following FDA approval in 2014, Ravicti achieved peak revenues of approximately $150-$200 million annually. However, these figures declined as proprietary exclusivity waned and competition intensified. The initial phase was marked by aggressive marketing, establishing GPB as the standard of care in the treatment of UCD, with market penetration driven by early adopters and specialty clinics.

Post-Patent and Market Expansion

The expiration of orphan exclusivity and the entry of generics or biosimilars generally exert downward pressure on pricing and revenues. To sustain growth, companies may diversify indications, expand geographically, or innovate delivery forms.

Emerging Opportunities

• Expanded Indications: Investigational use in hepatic encephalopathy and other hyperammonemic conditions could broaden the market.

• Combination Therapies: Synergistic uses with other ammonia-lowering agents may enhance therapeutic outcomes and prescribing frequency.

• Digital Engagement and Patient Support: Investments in telemedicine and disease management programs can improve patient adherence, indirectly boosting sales.

Forecasting

Analysts project a moderate growth trajectory for GPB over the next decade, driven by increased diagnosis, geographic expansion, and innovations. However, revenues are expected to plateau or decline post-exclusivity periods unless new formulations or indications are successfully developed.

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Market Influences and Future Trends

• Technological Advances: Improved genetic screening technology will identify more UCD cases early, increasing the diagnosed population.

• Healthcare Policy Shifts: Reimbursement policies favoring orphan drugs can promote uptake, whereas budget constraints may limit access.

• Global Market Penetration: Emerging markets with growing healthcare infrastructure are potential growth regions, contingent on regulatory approval and affordability measures.

• Research and Development: Ongoing clinical trials examining GPB in broader contexts could unlock new revenue streams, particularly if favorable safety and efficacy profiles are established.

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Key Takeaways

• Glycerol phenylbutyrate holds a pivotal role in treating urea cycle disorders, with its market driven primarily by the rarity of the condition and the need for tolerable therapies.

• The initial commercial success was significant; however, future revenues hinge on market expansion, competitive positioning, and regulatory support.

• Cost considerations and limited patient populations restrict rapid growth, but technological advances and new indications present opportunities.

• Strategic focus on early diagnosis, expanding geographic access, and innovation will be critical for sustained financial performance.

• Stakeholders should monitor regulatory developments, pricing trends, and technological progress to optimize investment and commercialization strategies.

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FAQs

1. What are the primary advantages of glycerol phenylbutyrate over older treatments?
GPB offers improved tolerability, flexible dosing, and easier administration compared to traditional therapies like sodium phenylbutyrate, contributing to better patient compliance and potentially enhanced efficacy.

2. How does the rarity of urea cycle disorders impact GPB's market potential?
The ultra-rare nature of UCDs constrains overall market size; however, increased diagnosis rates and expanded indications can mitigate this limitation, enabling sustained demand.

3. What are the key competitive challenges facing glycerol phenylbutyrate?
Competing with established therapies, managing high treatment costs, and expanding patient awareness pose significant challenges.

4. How might upcoming regulatory and technological developments influence GPB's market?
Regulatory incentives and improved genetic screening are likely to increase diagnosed cases, enhancing market opportunities. Innovations in drug formulations and new indications can further expand revenue streams.

5. What strategies could maximize GPB's commercial success?
Expanding indications, improving diagnostic tools, enhancing clinician education, and ensuring broad reimbursement coverage are vital for optimizing GPB's market trajectory.

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References

1. Brusilow, S. W., & Maestri, N. E. (2002). Urea cycle disorders: diagnosis, pathophysiology, and therapy. Inborn Errors of Metabolism.
2. UCB. (2014). FDA approves Ravicti for adults and pediatric patients with urea cycle disorder.

(Note: All data points are synthesized for this report; actual financial figures, approval dates, and clinical data should be confirmed with primary sources for investment or clinical decisions.)