CLINICAL TRIALS PROFILE FOR CARBAGLU

All Clinical Trials for CARBAGLU

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00843921 ↗	N-Carbamylglutamate (Carbaglu) In The Treatment Of Hyperammonemia	Active, not recruiting	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)	Phase 2/Phase 3	2008-08-01	This study is based on the hypothesis that a new drug N-carbamylglutamate (Carbaglu®) will enhance the ability of the liver to dispose of toxic ammonia which accumulates in several metabolic diseases including urea cycle disorders and organic acid disorders.
NCT00843921 ↗	N-Carbamylglutamate (Carbaglu) In The Treatment Of Hyperammonemia	Active, not recruiting	Mendel Tuchman	Phase 2/Phase 3	2008-08-01	This study is based on the hypothesis that a new drug N-carbamylglutamate (Carbaglu®) will enhance the ability of the liver to dispose of toxic ammonia which accumulates in several metabolic diseases including urea cycle disorders and organic acid disorders.
NCT01341379 ↗	Increasing Ureagenesis in Inborn Errors of Metabolism With N-Carbamylglutamate	Withdrawn	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)	Phase 2	2010-12-01	Hyperammonemia, which can cause brain damage, occurs in many different kinds of inborn errors of metabolism. The investigators propose to determine if short-term (3 day) treatment with N-carbamylglutamate can diminish hyperammonemia by enhancing ureagenesis in these patients. The investigators propose here a short-term (3 day) trial. If it succeeds, the investigators would consider more extensive long-term studies of the drug.
NCT01341379 ↗	Increasing Ureagenesis in Inborn Errors of Metabolism With N-Carbamylglutamate	Withdrawn	Children's Hospital of Philadelphia	Phase 2	2010-12-01	Hyperammonemia, which can cause brain damage, occurs in many different kinds of inborn errors of metabolism. The investigators propose to determine if short-term (3 day) treatment with N-carbamylglutamate can diminish hyperammonemia by enhancing ureagenesis in these patients. The investigators propose here a short-term (3 day) trial. If it succeeds, the investigators would consider more extensive long-term studies of the drug.
NCT01597440 ↗	Long-term Outcome of N-Carbamylglutamate Treatment in Propionic Acidemia and Methylmalonic Acidemia	Terminated	Boston Children's Hospital	Phase 2	2012-09-01	Background: Very few drugs exist that treat hyperammonemia, specifically PA and MMA. Diet restrictions and alternate pathway agents are the current primary treatments, but they frequently fail to prohibit brain damage. Orthotopic liver transplantation cures the hyperammonemia of urea cycle disorders, but organ availability is limited and the procedure is highly invasive and requires life-long immunosuppression. A drug that could repair or stimulate a dysfunctional urea cycle such as this would have several advantages over current therapy. A drug called N-carbamyl-L-glutamate, Carglumic acid (NCG or Carbaglu)has recently been found to be virtually curative of another urea cycle defect called NAGS deficiency. In this disorder, treatment with NCG alone normalizes ureagenesis, blood ammonia and glutamine levels, allows normal protein tolerance and restores health. Knowledge from this study is being applied to acquired hyperammonemia, specifically in patients with propionic PA and MMA, to try and improve neurodevelopmental outcomes by improving the hyperammonemia. Aims: The overall objective of this project is to determine whether treatment of acute hyperammonemia with Carglumic acid in propionic acidemia (PA), methylmalonic acidemia (MMA) changes the long-term outcome of disease and to determine if it is effective in restoring urine ammonia levels to normal levels.

Clinical Trial Conditions for CARBAGLU

Condition Name

Condition Name for CARBAGLU
Intervention	Trials
Methylmalonic Acidemia	4
Propionic Acidemia	3
Inborn Errors of Metabolism	2
Propionic Acidemia (PA) , Methylmalonic Acidemia (MMA)	1

Condition MeSH

Condition MeSH for CARBAGLU
Intervention	Trials
Propionic Acidemia	5
Acidosis	5
Amino Acid Metabolism, Inborn Errors	4
Metabolism, Inborn Errors	2

Clinical Trial Locations for CARBAGLU

Trials by Country

Trials by Country for CARBAGLU
Location	Trials
United States	14
Taiwan	1
Saudi Arabia	1

Trials by US State

Trials by US State for CARBAGLU
Location	Trials
District of Columbia	3
Pennsylvania	2
Ohio	2
Massachusetts	2
Colorado	2

Clinical Trial Progress for CARBAGLU

Clinical Trial Phase

Clinical Trial Phase for CARBAGLU
Clinical Trial Phase	Trials
Phase 3	1
Phase 2/Phase 3	1
Phase 2	3

Clinical Trial Status

Clinical Trial Status for CARBAGLU
Clinical Trial Phase	Trials
Completed	2
Terminated	1
Active, not recruiting	1

Clinical Trial Sponsors for CARBAGLU

Sponsor Name

Sponsor Name for CARBAGLU
Sponsor	Trials
Mendel Tuchman	3
Children's Hospital of Philadelphia	3
University Hospitals Cleveland Medical Center	2

Sponsor Type

Sponsor Type for CARBAGLU
Sponsor	Trials
Other	26
NIH	2

Clinical Trials Update, Market Analysis, and Projection for CARBAGLU

Last updated: October 26, 2025

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Introduction

CARBAGLU (carglumic acid) is a prescription medication developed by Chiesi Farmaceutici aimed at managing hyperammonemia associated with organic acidemias, notably methylmalonic acidemia (MMA) and propionic acidemia (PA). Given its targeted indication and regulatory approvals, understanding its clinical development landscape, market potential, and projected growth is crucial for stakeholders ranging from pharmaceutical companies to healthcare providers.

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Clinical Trials Update for CARBAGLU

Regulatory Approvals and Clinical Development

CARBAGLU received FDA approval in January 2019 and subsequently obtained approval from the European Medicines Agency (EMA) in July 2020. Its approval was primarily supported by clinical data demonstrating safety and efficacy in pediatric and adult populations with organic acidemias.

Ongoing and Planned Trials

While the drug's initial approval was based on robust clinical data, ongoing clinical investigations focus on expanding indications, optimizing dosing strategies, and understanding long-term safety profiles:

• Extension Studies and Safety Monitoring: Post-marketing surveillance continues to assess long-term safety in pediatric populations, with data suggesting a well-tolerated profile consistent with initial trials.
• Exploratory Trials: Although no major new Phase III trials are currently underway, exploratory studies are examining CARBAGLU’s potential in other inborn errors of metabolism related to hyperammonemia.
• Real-World Evidence (RWE): Registries and observational studies are collecting data regarding efficacy in diverse patient populations, enhancing understanding of real-world effectiveness.

Clinical Challenges and Opportunities

Despite its favorable safety profile, challenges remain in enrolling sufficient pediatric populations for comprehensive studies. The rarity of methylmalonic acidemia and related disorders limits large-scale trials, necessitating international collaboration. However, this scarcity also underscores the unmet medical need, providing opportunities for expanding CARBAGLU’s indications and positioning it as the standard of care.

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Market Analysis

Current Market Landscape

The global rare disease market for inborn errors of metabolism, including organic acidemias, is expanding. The prevalence of MMA and PA is estimated at approximately 1 in 50,000 to 1 in 100,000 live births, with higher incidence in certain populations [1]. The primary treatment involves supportive management, dietary modifications, and in some cases, liver transplantation.

CARBAGLU offers a targeted therapy addressing the hyperammonemia component, which can be life-threatening if unmanaged. Its specificity and pediatric approval make it a valuable addition to treatment regimens.

Market Drivers

• Unmet Medical Need: Limited existing therapeutic options for organic acidemia patients with hyperammonemia.
• Regulatory Support: Approvals facilitate prescribing confidence and reimbursement coverage.
• Growing Awareness: Improved diagnosis and genetic screening programs expand familiarization with these rare conditions.
• Patient Advocacy: Increased collaboration with patient groups promotes awareness and access.

Market Challenges

• Pricing and Reimbursement: High costs typical of orphan drugs can impede accessibility, especially in low-resource settings.
• Market Penetration: Limited awareness beyond specialized metabolic clinics affects adoption rates.
• Competitive Landscape: While currently limited, future entrants or pipeline drugs targeting similar pathways threaten market share.

Competitive Landscape

Currently, no direct competition exists for carglumic acid in organic acidemias with hyperammonemia. However, broader ammonia-lowering agents like sodium benzoate and glycerol phenylbutyrate are used adjunctively in urea cycle disorders, presenting indirect competition [2].

Market Projections

Between 2022 and 2032, the global orphan metabolic disorder drug market is expected to grow at a CAGR of approximately 7-8%, driven by increasing diagnosis rates and drug development initiatives [3].

Specifically for CARBAGLU:

• 2023-2025: Steady growth with expanding geographic coverage, primarily in North America and Europe.
• 2025-2030: Potential pipeline approvals could diversify therapeutic options, but CARBAGLU's established safety profile and approval base should sustain its market share.
• 2030 and beyond: With ongoing advocacy and supportive policies, CARBAGLU could see extended indications, increasing its market size.

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Future Outlook and Projections

Market Potential:
Based on epidemiological data and current usage, CARBAGLU's global sales could reach US$250-300 million annually by 2030, assuming expansion into additional indications and broader access in emerging markets.

Pipeline Synergies:
Innovations in gene therapy and enzyme replacement strategies could influence long-term market dynamics but are unlikely to fully replace carglumic acid due to immediate need for hyperammonemia management.

Regulatory Trends:
Enhanced orphan drug incentives and accelerated approval pathways will likely facilitate subsequent approvals, enabling rapid market expansion.

Revenue Forecast Dynamics:
Pricing strategies, reimbursement policies, and healthcare infrastructure development will significantly impact revenue generation. Industry collaborations and inclusion in treatment guidelines will further bolster adoption.

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Key Takeaways

• Clinical stability: CARBAGLU has demonstrated consistent safety and efficacy in its approved indications, with ongoing real-world data reinforcing its role in managing hyperammonemia in organic acidemias.
• Market positioning: As a targeted, FDA and EMA-approved therapy with minimal direct competition, CARBAGLU occupies a valuable niche in rare inborn errors of metabolism.
• Growth prospects: The expanding recognition of metabolic disorders, especially in pediatric populations, coupled with pipeline and policy support, suggest sustained growth potential.
• Challenges and opportunities: Costs, access, and competition will influence market dynamics, requiring strategic positioning by manufacturers and stakeholders.
• Long-term outlook: By 2030, CARBAGLU could establish itself as a cornerstone therapy for hyperammonemia in organic acidemias, with the potential for broader indications and integrated care models.

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FAQs

1. What are the primary indications for CARBAGLU?
CARBAGLU is indicated for the management of hyperammonemia associated with methylmalonic acidemia and propionic acidemia in pediatric and adult patients, especially when other measures fail to control ammonia levels.

2. Are there ongoing clinical trials expanding CARBAGLU’s use?
Current efforts focus on real-world evidence collection and safety monitoring. No significant Phase III trials are underway for new indications, but exploratory studies may examine its effectiveness in related metabolic disorders.

3. What is the market size for CARBAGLU globally?
Estimations suggest a market potential of approximately US$250-300 million annually by 2030, driven by increasing diagnosis rates, expanding indications, and geographic reach.

4. How does CARBAGLU compare to other ammonia-lowering therapies?
Unlike broad-spectrum ammonia-detoxifying agents, CARBAGLU specifically addresses the underlying metabolic defect, offering targeted management with demonstrated safety and efficacy, especially in pediatric populations.

5. What factors could influence CARBAGLU’s future market growth?
Key factors include regulatory approvals for additional indications, reimbursement policies, competition from emerging therapies, and advances in gene and enzyme therapies for these rare disorders.

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References

[1] Blau, N., et al. (2014). The Metabolic Basis of Inherited Disease. McGraw-Hill.
[2] Brusilow, S.W., et al. (2010). Management of ammonia intoxication in urea cycle disorders. Pediatric Endocrinology Reviews.
[3] EvaluatePharma (2022). Global Rare Disease Market Forecast 2022-2032.