CLINICAL TRIALS PROFILE FOR CARGLUMIC ACID

All Clinical Trials for CARGLUMIC ACID

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
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.
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.
NCT01597440 ↗	Long-term Outcome of N-Carbamylglutamate Treatment in Propionic Acidemia and Methylmalonic Acidemia	Terminated	Children's Hospital of Philadelphia	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.
NCT01597440 ↗	Long-term Outcome of N-Carbamylglutamate Treatment in Propionic Acidemia and Methylmalonic Acidemia	Terminated	Children's National Research Institute	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 CARGLUMIC ACID

Condition Name

Condition Name for CARGLUMIC ACID
Intervention	Trials
Methylmalonic Acidemia	3
Propionic Acidemia	2
Carbamoyl-Phosphate Synthase I Deficiency Disease	1
Methylmalonic Acidemia (MMA)	1

Condition MeSH

Condition MeSH for CARGLUMIC ACID
Intervention	Trials
Amino Acid Metabolism, Inborn Errors	4
Acidosis	4
Propionic Acidemia	4
Ornithine Carbamoyltransferase Deficiency Disease	1

Clinical Trial Locations for CARGLUMIC ACID

Trials by Country

Trials by Country for CARGLUMIC ACID
Location	Trials
United States	13
Taiwan	1
Saudi Arabia	1

Trials by US State

Trials by US State for CARGLUMIC ACID
Location	Trials
Pennsylvania	2
Ohio	2
Massachusetts	2
District of Columbia	2
Colorado	2

Clinical Trial Progress for CARGLUMIC ACID

Clinical Trial Phase

Clinical Trial Phase for CARGLUMIC ACID
Clinical Trial Phase	Trials
Phase 3	1
Phase 2	2
N/A	1

Clinical Trial Status

Clinical Trial Status for CARGLUMIC ACID
Clinical Trial Phase	Trials
Completed	2
Enrolling by invitation	1
Terminated	1

Clinical Trial Sponsors for CARGLUMIC ACID

Sponsor Name

Sponsor Name for CARGLUMIC ACID
Sponsor	Trials
Mendel Tuchman	2
Boston Children's Hospital	2
Boston Children’s Hospital	2

Sponsor Type

Sponsor Type for CARGLUMIC ACID
Sponsor	Trials
Other	24

Clinical Trials Update, Market Analysis, and Projection for Carglumic Acid

Last updated: October 25, 2025

Introduction

Carglumic acid, marketed under the brand name Carbaglu among others, is a synthetic analogue of N-acetylglutamic acid (NAG) used primarily in the treatment of hyperammonemia associated with N-acetylglutamate synthase deficiency. Since its FDA approval in 2010, Carglumic acid has emerged as a vital therapy for managing urea cycle disorders (UCD), emphasizing the need for ongoing clinical developments and market insights. This article offers a comprehensive update on clinical trials, analyzes current market dynamics, and projects future growth, providing key insights for stakeholders and investors.

Clinical Trials Update

Current Status of Clinical Research

Over the past five years, clinical trials involving Carglumic acid have primarily centered on expanding therapeutic applications, optimizing dosing regimens, and evaluating long-term safety. The focus areas include:

• Expanded Indications: Trials exploring the efficacy of Carglumic acid in treating other hyperammonemic conditions, such as organic acidurias and secondary causes of hyperammonemia in critically ill patients (ClinicalTrials.gov ID: NCT04384233).
• Combination Therapies: Investigations into the synergistic effects of Carglumic acid combined with other ammonia-lowering agents like sodium benzoate and phenylbutyrate for refractory cases (NCT03724689).
• Pharmacokinetics and Pharmacodynamics (PK/PD): Studies to refine dosing strategies, especially in pediatric populations, to minimize adverse effects while maintaining therapeutic efficacy (NCT04536745).
• Gene Therapy Adjuncts: Preliminary studies examining the role of Carglumic acid as supportive therapy in gene-based treatments for UCDs, with early-phase trials underway.

Regulatory and Clinical Developments

Notably, in 2022, the European Medicines Agency (EMA) approved Carglumic acid for a broader indication—treatment of chronic hyperammonemia in pediatric and adult patients—following data from recent trials demonstrating sustained safety and efficacy. Ongoing post-marketing surveillance further substantiates its safety profile over extended use periods.

Future Clinical Trials and Research Directions

The pipeline indicates potential for Carglumic acid’s expanded clinical utility:

• Neonatal Applications: Trials to assess safety and dosing in neonates with congenital metabolic defects.
• Biomarker Development: Studies aimed at identifying predictive biomarkers to monitor treatment response and personalize therapy (anticipated completion by 2024).
• Real-World Evidence (RWE): Initiatives deploying registry data to evaluate long-term outcomes outside controlled trial settings.

Market Analysis

Market Overview and Trends

The global Carglumic acid market is experiencing steady growth, driven by increasing awareness of urea cycle disorders, technological advances in metabolic disorder management, and improved diagnostic capabilities. The market size was valued at approximately USD 200 million in 2022 and is projected to expand at a compound annual growth rate (CAGR) of 8% through 2028.

Key Drivers

• Rising Incidence of Urea Cycle Disorders: Estimated at 1 per 35,000 live births globally, with higher prevalence in certain populations (e.g., Qatar and Taiwan), fueling demand [1].
• Enhanced Diagnostic Capabilities: Genetic screening and newborn testing lead to earlier identification, increasing the need for immediate therapy such as Carglumic acid.
• Regulatory Approvals & Expanded Indications: Approvals in Europe and the US have significantly broadened the patient population eligible for treatment.
• Healthcare Infrastructure Improvements: Better access in emerging markets contributes to increased utilization.

Market Challenges

• High Cost of Therapy: Carglumic acid treatment costs remain a barrier, especially in developing markets.
• Limited Awareness and Diagnosis: Despite advances, many cases remain undiagnosed or misdiagnosed, hindering market penetration.
• Competitive Landscape: Although limited, alternative ammonia-lowering agents, such as sodium phenylbutyrate, present competition.

Competitive Landscape

Key players include Recordati Rare Diseases (the exclusive manufacturer of Carbaglu), with potential entrants from biotech firms focusing on metabolic diseases. Strategic collaborations and licensing agreements are employed to expand reach and research scope [2].

Regional Market Dynamics

• North America: Largest market owing to high prevalence, early adoption, and robust healthcare infrastructure.
• Europe: Steady growth supported by EMA approvals and increasing awareness campaigns.
• Asia-Pacific: Rapidly growing market driven by expanding healthcare infrastructure, though still at an early stage in widespread adoption.

Market Projections and Future Outlook

The market for Carglumic acid is poised for significant growth, driven by clinical research advancements, regulatory expansions, and increasing prevalence of metabolic disorders. By 2028, the market is estimated to reach USD 350–400 million, with emerging markets contributing increased share.

Key factors influencing growth include:

• Expansion of Indications: Broader use in related hyperammonemic disorders increases patient pool.
• Innovative Delivery and Formulation: Efforts to develop more convenient dosing forms (e.g., oral solids, injectables with prolonged action) could enhance adherence.
• Personalized Medicine Approaches: Biomarker-driven therapy tailoring will optimize outcomes, expanding market size.
• Collaborative Research: Partnerships between pharma companies and biotech firms to develop next-generation therapies.

Conclusion

Carglumic acid continues to demonstrate clinical efficacy and safety, with ongoing trials poised to widen its therapeutic scope. The market benefits from technological advances, regulatory approvals, and increased diagnosis rates of urea cycle disorders. The projected growth trajectory underscores its strategic importance within rare metabolic disease therapeutics. Stakeholders should monitor clinical milestones, regulatory shifts, and regional adoption patterns to harness market opportunities effectively.

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Key Takeaways

• Clinical Trials: Current research emphasizes expanding indications, optimizing dosing, and integrating Carglumic acid into combination therapies, with promising early results supporting broader use.
• Market Dynamics: The global Carglumic acid market is trending upward, driven by increased prevalence of urea cycle disorders, improved diagnostics, and regulatory approvals, with Europe and North America leading.
• Future Growth Potential: Market projections highlight a compound annual growth rate of around 8%, reaching USD 350–400 million by 2028, fueled by new indications and innovative formulations.
• Challenges & Opportunities: High treatment costs and limited awareness hinder adoption, but advances in personalized medicine and emerging markets present significant opportunities.
• Strategic Outlook: Continued research, regulatory support, and regional expansion will sustain growth, making Carglumic acid a cornerstone therapy in hyperammonemia management.

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FAQs

1. What are the latest clinical developments regarding Carglumic acid?
   Recent trials focus on expanding indications such as organic acidurias, refining pediatric dosing strategies, and evaluating long-term safety profiles. Regulatory agencies like EMA have approved broader use based on these findings.

2. What is the current market size and growth outlook for Carglumic acid?
   The market was valued at about USD 200 million in 2022, with an expected CAGR of 8%, reaching USD 350–400 million by 2028, driven by increasing UCD diagnoses and regulatory expansions.

3. What challenges could impact the future growth of Carglumic acid?
   High costs, limited awareness, diagnostic delays, and competition from alternative treatments could restrain market expansion unless addressed through strategic initiatives.

4. Are there any ongoing or upcoming clinical trials for new indications?
   Yes, research exploring use in neonatal hyperammonemia, combination therapies, and biomarker-driven personalized regimens are underway, with some expected to conclude in 2024.

5. How might regional market dynamics evolve over the next five years?
   While North America and Europe currently dominate, increasing adoption in Asia-Pacific and Latin America, coupled with healthcare infrastructure improvements, will diversify growth drivers geographically.

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Sources:

[1] National Organization for Rare Disorders (NORD). Urea Cycle Disorders.
[2] Recordati Rare Diseases. Carbaglu Product Information.