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.

Clinical Trial Conditions for carglumic acid

Condition Name

Condition Name for carglumic acid
Intervention	Trials
Methylmalonic Acidemia	3
Propionic Acidemia	2
Propionic Acidemia (PA)	1

Condition MeSH

Condition MeSH for carglumic acid
Intervention	Trials
Propionic Acidemia	4
Amino Acid Metabolism, Inborn Errors	4
Acidosis	4

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
Terminated	1
Enrolling by invitation	1

Clinical Trial Sponsors for carglumic acid

Sponsor Name

Sponsor Name for carglumic acid
Sponsor	Trials
University Hospitals Cleveland Medical Center	2
University of California, Los Angeles	2
Mendel Tuchman	2

Sponsor Type

Sponsor Type for carglumic acid
Sponsor	Trials
Other	24

CARGLUMIC ACID: Clinical Trials, Market Analysis, and Projections

Introduction to Carglumic Acid

Carglumic acid, marketed as CARBAGLU, is a medication used to treat hyperammonemia, a condition characterized by elevated levels of ammonia in the blood. This condition can arise from various metabolic disorders, including urea cycle disorders, propionic acidemia (PA), and methylmalonic acidemia (MMA).

Clinical Trials and Efficacy

FDA Approval and Clinical Trials

In January 2021, the U.S. Food and Drug Administration (FDA) approved a new indication for CARBAGLU (carglumic acid) tablets for the treatment of acute hyperammonemia associated with PA and MMA in pediatric and adult patients. This approval was supported by a randomized, double-blind, placebo-controlled, multicenter clinical trial. The trial involved 24 patients and evaluated 90 hyperammonemic episodes, showing that patients receiving CARBAGLU had a quicker reduction in ammonia levels compared to those receiving a placebo. The primary endpoint was the time from the first dose to the earlier of blood ammonia level below 50 micromol/L or hospital discharge, with a higher proportion of CARBAGLU-treated episodes reaching this endpoint within the first three days of treatment[1].

Long-term Effectiveness

A prospective, multicenter, randomized, parallel-group, open-label clinical trial evaluated the long-term effectiveness of carglumic acid in patients with PA and MMA. The study found that using carglumic acid in addition to standard treatment significantly reduced the number of emergency room (ER) admissions due to hyperammonemia. Over a two-year follow-up, the mean number of ER admissions was 6.31 for the carglumic acid arm, compared to 12.76 for the standard treatment arm, highlighting a significant reduction in hyperammonemic episodes[4].

Adverse Reactions and Safety

In the clinical trials, at least one adverse reaction was reported in 42.2% of the 90 hyperammonemic episodes. While the medication is generally well-tolerated, monitoring for potential side effects is crucial to ensure patient safety[1].

Market Analysis

Current Market Size and Growth

The global carglumic acid market was valued at approximately USD 148.6 million in 2023. It is projected to grow at a Compound Annual Growth Rate (CAGR) of around 7.1% to 7.38% from 2024 to 2032 or 2033, reaching an estimated USD 280 million to USD 281.81 million by the end of the forecast period[2][5].

Key Drivers of Market Growth

Several factors are driving the growth of the carglumic acid market:

• Rising Prevalence of Metabolic Diseases: The increasing incidence of metabolic disorders such as type 2 diabetes, hypertension, and non-alcoholic fatty liver disease (NAFLD) is a significant driver. These conditions often lead to hyperammonemia, thereby increasing the demand for carglumic acid[2].
• Growing Awareness and Diagnosis of Rare Diseases: Heightened awareness and improved diagnostic techniques for rare diseases like PA and MMA are contributing to the market's growth[5].
• Impact of COVID-19: The COVID-19 pandemic has also played a role, as hyperammonemia can be a complication in severe COVID-19 cases, particularly those involving disseminated cryptococcal infections[3].

Market Segmentation

The carglumic acid market is segmented based on dosage form, distribution channel, and region.

• Dosage Form: The market includes orally disintegrating tablets, dispersible tablets, and other dosage forms. Dispersible tablets held the leading revenue share in 2023 and are expected to continue growing[2].
• Distribution Channel: Hospital pharmacies dominate the market, followed by retail and online pharmacies. In 2023, hospital pharmacies accounted for around USD 77 million in revenue[2].
• Region: North America is the largest market for carglumic acid, driven by high incidences of metabolic disorders and cancers, as well as significant research and development activities by pharmaceutical companies[3][5].

Competitive Landscape

The carglumic acid market is competitive, with several large multinationals and small to mid-sized companies involved. Key market strategies include the development and launch of novel products based on advanced technologies. Companies like Recordati Rare Diseases Inc. are prominent players in this market[2].

Future Projections and Trends

Market Expansion

The market is expected to expand significantly due to the increasing incidence of metabolic disorders and the growing awareness of rare diseases. Regulatory support from bodies like the FDA also contributes to market growth by ensuring the safety and efficacy of carglumic acid products[3].

Technological Advancements

Continuous research and development in the pharmaceutical sector are likely to introduce new and improved dosage forms and treatment protocols, further driving the market's growth.

Regional Growth

North America is anticipated to continue holding the largest share of the market, followed by other regions where the prevalence of metabolic and rare diseases is increasing[3][5].

Key Takeaways

• Clinical Efficacy: Carglumic acid has been shown to be effective in reducing ammonia levels and the number of hyperammonemic episodes in patients with PA and MMA.
• Market Growth: The global carglumic acid market is projected to grow at a CAGR of around 7.1% to 7.38% from 2024 to 2032 or 2033.
• Key Drivers: Rising prevalence of metabolic diseases, growing awareness of rare diseases, and the impact of COVID-19 are key drivers of market growth.
• Market Segmentation: The market is segmented by dosage form, distribution channel, and region, with North America being the largest market.

FAQs

What is carglumic acid used for?

Carglumic acid is used to treat hyperammonemia, a condition characterized by elevated levels of ammonia in the blood, often associated with metabolic disorders such as propionic acidemia (PA) and methylmalonic acidemia (MMA).

What was the outcome of the FDA-approved clinical trial for carglumic acid?

The clinical trial showed that patients receiving carglumic acid had a quicker reduction in ammonia levels compared to those receiving a placebo, with a higher proportion reaching the primary endpoint within the first three days of treatment[1].

How does the COVID-19 pandemic impact the carglumic acid market?

The COVID-19 pandemic has increased the demand for carglumic acid due to the potential for hyperammonemia as a complication in severe COVID-19 cases, particularly those involving disseminated cryptococcal infections[3].

What are the main segments of the carglumic acid market?

The market is segmented by dosage form (orally disintegrating tablets, dispersible tablets, etc.), distribution channel (hospital pharmacies, retail pharmacies, etc.), and region (with North America being the largest market)[2].

What is the projected growth rate of the carglumic acid market?

The global carglumic acid market is projected to grow at a CAGR of around 7.1% to 7.38% from 2024 to 2032 or 2033[2][5].

Who are the key players in the carglumic acid market?

Key players include Recordati Rare Diseases Inc. and other pharmaceutical companies involved in the development and distribution of carglumic acid products[2].

Sources

1. Recordati Rare Diseases: CARBAGLU New Indication PA MMA Press Release.
2. Global Market Insights: Carglumic Acid Market Forecasts 2024-2032 | Statistics Report.
3. Mordor Intelligence: Carglumic Acid Market Size & Share Analysis.
4. PubMed: Long-term effectiveness of carglumic acid in patients with propionic acidemia and methylmalonic acidemia.
5. The Brainy Insights: Carglumic Acid Market Size, Trend Analysis, Insights.