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
Horizon Therap Us	RAVICTI	glycerol phenylbutyrate	LIQUID;ORAL	203284-001	Feb 1, 2013	AA	RX	Yes	Yes
Horizon Therap Us	RAVICTI	glycerol phenylbutyrate	LIQUID;ORAL	203284-001	Feb 1, 2013	AA	RX	Yes	Yes
Ph Health	GLYCEROL PHENYLBUTYRATE	glycerol phenylbutyrate	LIQUID;ORAL	205742-001	Dec 2, 2021	AA	RX	No	No
Horizon Therap Us	RAVICTI	glycerol phenylbutyrate	LIQUID;ORAL	203284-001	Feb 1, 2013	AA	RX	Yes	Yes
Horizon Therap Us	RAVICTI	glycerol phenylbutyrate	LIQUID;ORAL	203284-001	Feb 1, 2013	AA	RX	Yes	Yes
Horizon Therap Us	RAVICTI	glycerol phenylbutyrate	LIQUID;ORAL	203284-001	Feb 1, 2013	AA	RX	Yes	Yes

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

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
Ecuador	SP14024561	MÉTODOS DE MONITOREO TERAPÉUTICO DE PROFÁRMACOS DE ÁCIDO FENILACÉTICO
Australia	2012316750	Methods of therapeutic monitoring of nitrogen scavenging drugs
Australia	2018200163	Methods of therapeutic monitoring of phenylacetic acid prodrugs
European Patent Office	2760479	AGENT D'ÉLIMINATION D'AZOTE POUR L'UTILISATION DANS UN PROCÉDÉ DE THÉRAPIE D'UN SYNDROME DE RÉTENTION D'AZOTE (NITROGEN SCAVENGING DRUG FOR USE IN A METHOD OF TREATING A NITROGEN RETENTION DISORDER)
Australia	2012377389	Methods of therapeutic monitoring of phenylacetic acid prodrugs
Japan	6073898
Portugal	3133396

Supplementary Protection Certificates for GLYCEROL PHENYLBUTYRATE

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
2330892	2016023	Norway		PRODUCT NAME: GLYCEROLFENYLBUTYRAT; REG. NO/DATE: EU/1/15/1062 20151210
2330892	2016C/074	Belgium		PRODUCT NAME: GLYCEROLFENYLBUTYRAAT; AUTHORISATION NUMBER AND DATE: EU/1/15/1062 20151201
2330892	635	Finland
2330892	SPC/GB17/001	United Kingdom		PRODUCT NAME: GLYCEROL PHENYLBUTYRATE; REGISTERED: UK EU/1/15/1062 20151201; UK PLGB53487/0001 20151201
2330892	C20160044 00204	Estonia		PRODUCT NAME: GLUETSEROOLFENUEUELBUTUERAAT;REG NO/DATE: EU/1/15/1062 01.12.2015
2330892	PA2016041	Lithuania		PRODUCT NAME: GLICEROLIO FENILBUTIRATAS; REGISTRATION NO/DATE: EU/1/15/1062 20151127
2330892	2016/064	Ireland		PRODUCT NAME: GLYCEROL PHENYLBUTYRATE; REGISTRATION NO/DATE: EU/1/15/1062 20151201

Glycerol Phenylbutyrate (Glycerol PB): Market Dynamics and Financial Trajectory

Last updated: April 24, 2026

What is the product and where does it sit commercially?

Glycerol phenylbutyrate (GPB) is the prodrug of phenylacetate/phenylbutyrate metabolites used to reduce ammonia in patients with urea cycle disorders (UCD). Commercially, GPB is associated with Horizon Therapeutics’ Ammonaps franchise successor positioning and a broader portfolio shift from older sodium phenylbutyrate approaches toward once-daily, prodrug formulations that reduce treatment burden.

For business planning, the key commercialization anchor is that GPB competes within a specialty, gene-therapy-adjacent UCD market where uptake depends on:

• payer coverage decisions for ultra-orphan and high-cost chronic therapies
• clinical adoption through metabolic control and tolerability
• distribution access through specialty pharmacies and hospital formularies

GPB’s competitive set includes older phenylbutyrate regimens and, selectively, newer or pipeline ammonia-lowering therapies in development. Market growth is limited by the small UCD population, but pricing and persistency can drive revenue even without large patient-count expansions.

How does pricing and reimbursement shape demand?

GPB is a high-cost chronic therapy. In this segment, revenue is driven by a combination of:

• net price after rebates and specialty pharmacy contracting
• commercial and Medicaid coverage breadth for rare-disease indications
• prior authorization thresholds (biochemical ammonia criteria, confirmed diagnosis, prior therapy requirements)
• treatment continuity as patients remain on therapy for life absent transplant or durable gene-therapy response

In practice, payer dynamics tend to create a pattern where early market entry revenue can be uneven until coding, formulary positioning, and contracting normalize. Once access stabilizes, the demand curve typically becomes persistency-led rather than incidence-led.

What market dynamics govern uptake?

UCD-specific adoption is typically constrained by diagnosis timing and lifelong adherence. For GPB, uptake drivers and friction points track three channels:

1. Clinical outcomes and tolerability

   • UCD is managed through biochemical control. GPB’s value proposition centers on ammonia reduction with a regimen profile that supports adherence.
   • Treatment switching depends on clinician comfort, patient experience, and payer step edits.

2. Care pathway and distribution

   • UCD care is routed through metabolic specialists and specialty centers.
   • Access is governed by specialty pharmacy fill rates and hospital pharmacy agreements for pediatrics and transition-of-care.

3. Therapy mix in rare disease

   • Even with no direct biologic substitution, competitor products can limit uptake through formularies and “preferred therapy” lists.
   • Gene-therapy announcements can alter payer risk posture and clinician selection behavior, primarily at the margin for newly diagnosed or borderline-eligibility patients.

What does the financial trajectory look like at a high level?

GPB’s financial trajectory is best described as a revenue scaling phase followed by maturity dynamics common to ultra-orphan specialty drugs:

• Pre-maturity: adoption expands as formulary coverage and specialty distribution stabilize; revenue growth tracks new starts and switching.
• Maturity: growth increasingly reflects patient retention, limited switching headroom, and incremental expansion tied to diagnosis and age-band dosing adoption.
• Late-cycle pressure points: pricing pressure from payers, competitor entry, and the switching cost of any alternative ammonia-lowering therapy.

Because GPB’s market size is small, minor changes in patient starts, discontinuation, or contract terms can materially affect quarterly revenue. This is consistent with typical economics for ultra-orphan chronic therapies.

How do competitors and pipeline risk affect revenue?

The main financial risk for GPB is not only direct substitution but also formulary and contract placement over time:

• Legacy phenylbutyrate regimens may remain preferred in certain payers or geographies due to entrenched contracting.
• Other ammonia-lowering agents in development can create incremental price pressure or “preferred product” switches.
• Gene therapy can reduce long-term patient need for chronic metabolic drugs for a subset of eligible patients. Even when adoption is modest initially, it can influence payer contracting and physician behavior.

In ultra-rare segments, competition tends to show up first through:

• payer coverage restrictions and step therapy
• negotiation of net price and rebates
• increased scrutiny of biochemical endpoints required to approve continuation

What investment-relevant financial metrics matter most for GPB?

For an ultra-orphan chronic therapy like GPB, investors and R&D strategists should weight these metrics more heavily than top-line alone:

• Net revenue growth driven by:
  • new starts
  • therapy switching (from older regimens)
  • persistency (low discontinuation)
• Gross-to-net trend (rebates, discounts, access-related adjustments)
• Specialty pharmacy fill stability
• Pediatric vs adult mix shifts (if dosing and access differ by segment)
• Contract renegotiation cadence (rare-disease payers can reprice on cycle changes)

Even without large changes in patient numbers, net price and rebate rate movement can explain major revenue variance.

What are the demand anchors that typically support revenue stability?

GPB’s revenue stability is driven by three anchors:

1. Therapy is chronic

   • Discontinuation is rare unless the patient is transplanted or transitions to a durable alternative therapy.

2. Clinical endpoints are objective

   • Reimbursement and continuation approvals rely on biochemical measures, reducing payer arbitrariness once stable control is established.

3. Treatment burden affects persistence

   • If GPB improves adherence versus older phenylbutyrate strategies, it reduces discontinuation risk and supports higher utilization per treated patient.

What commercialization events can shift the revenue curve?

Revenue inflection typically comes from a limited set of events:

• Expanded payer access (moving from narrow to broader coverage criteria)
• Updated labeling or dosing guidance that removes operational barriers
• New patient population subgroups (age bands, additional phenotypes within UCD coverage)
• Competitive repositioning from other products that changes preferred formulary status

In small markets, each event can push utilization meaningfully even if absolute patient counts remain low.

What is the regulatory and corporate backdrop impacting market expectations?

GPB sits inside the long-term UCD strategy of major pharma that has concentrated on improving convenience and adherence compared with sodium phenylbutyrate. Horizon’s role in GPB’s commercialization has linked product performance to:

• specialty rare-disease execution
• payer contracting capability
• continued clinical evidence generation and label maintenance

For market dynamics, corporate priorities also matter. Rare-disease portfolios attract capital based on perceived durability of cash flows. Any shift in corporate resource allocation away from GPB, or a re-weighting toward pipeline assets, can affect launch cadence, payer support programs, and label expansions.

How does patient economics translate into revenue mechanics?

In ultra-orphan therapies:

• revenue equals treated patient count times annualized net price
• net price depends on contract terms and rebate structure
• patient count depends on diagnosis rates, time-to-treatment initiation, and switch decisions

This makes GPB’s financial trajectory sensitive to:

• diagnosis timing and newborn screening follow-through (where applicable)
• metabolic specialist prescribing behavior
• continuity programs that reduce gaps in therapy

Even modest improvement in access can drive a step-function increase in treated patients, because the starting base is small.

What are the most likely phases of GPB’s financial trajectory (scenario map)?

The following phase map is useful for underwriting:

Phase	Time characteristics	Primary driver of revenue	Main risk
Scale-up	Initial adoption and payer normalization	New starts and formulary wins	Narrow coverage and step edits
Maturity	Broad access and stable prescribing	Persistency and limited switching	Net price pressure and contracting resets
Late-cycle	Margin compression and competitive substitution	Continued chronic utilization	Competitor entry or durable alternatives

This structure aligns with how specialty rare-disease products typically evolve after initial uptake.

Key takeaways

• GPB’s market dynamics are governed by chronic therapy economics, payer access mechanics, and persistency, not by large incidence expansion.
• Financial trajectory is best modeled as patient-count times net price, with quarterly variation often explained by rebate and contract dynamics rather than clinical surprises.
• Competitive risk comes through formulary positioning and payer step therapy, while longer-term risk comes from durable alternatives that can reduce long-term chronic drug need for eligible patients.

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FAQs

1) What drives GPB revenue growth most reliably?

Persistency and treated-patient expansion via stable coverage and specialty dispensing. In ultra-orphan settings, these dominate because incidence growth is slow.

2) How does reimbursement affect GPB quarterly performance?

Gross-to-net changes tied to rebates, specialty contracting, and access program criteria can move net revenue even if patient counts are stable.

3) What determines whether patients switch to GPB?

Clinician preference supported by ammonia control and tolerability, plus payer willingness to cover a switch from older phenylbutyrate regimens without restrictive step edits.

4) What competitor threats matter most for GPB?

Threats that change formulary preference and step-therapy pathways can reduce utilization. Longer-term, therapies that reduce the need for chronic ammonia-lowering drugs can compress the addressable population.

5) What underwriting metric should investors track continuously?

Net revenue growth relative to treated patients, with close monitoring of gross-to-net and specialty dispensing stability.

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References

[1] EMA. (n.d.). European public assessment reports for ammonia-lowering therapies in urea cycle disorders (UCD). European Medicines Agency.
[2] FDA. (n.d.). Labeling and approval history for glycerol phenylbutyrate and related ammonia-lowering therapies for UCD. U.S. Food and Drug Administration.
[3] Horizon Therapeutics. (n.d.). Company filings and investor presentations covering glycerol phenylbutyrate commercialization and financial reporting. Horizon Therapeutics.