CLINICAL TRIALS PROFILE FOR DEMSER

All Clinical Trials for DEMSER

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00581477 ↗	Treatment of Orthostatic Hypotension	Completed	Vanderbilt University	Phase 3	2004-01-01	The purpose of this study is to try different medications in patients with low blood pressure and other problems with their involuntary (autonomic) nervous system. The pharmacological trials in this study will perhaps lead to more effective treatment. This study consists of single dose trials, dose selection trials, 5-day trials and chronic (approximately 2 months) trials.
NCT00581477 ↗	Treatment of Orthostatic Hypotension	Completed	Vanderbilt University Medical Center	Phase 3	2004-01-01	The purpose of this study is to try different medications in patients with low blood pressure and other problems with their involuntary (autonomic) nervous system. The pharmacological trials in this study will perhaps lead to more effective treatment. This study consists of single dose trials, dose selection trials, 5-day trials and chronic (approximately 2 months) trials.
NCT00028106 ↗	131MIBG to Treat Malignant Pheochromocytoma	Completed	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)	Phase 2	2001-12-05	This study will evaluate the effectiveness of 131MIBG in treating malignant pheochromocytoma and whether sensitization medications improve the response to treatment. Pheochromocytoma is a rare type of tumor that usually occurs in the adrenal glands. The tumor cells release chemicals like adrenaline that can cause large increases in blood pressure and pulse rate, with serious health consequences. Tumor in the adrenal glands usually can be removed surgically, but if the pheochromocytoma is malignant-i.e., has spread to many sites in the body-or is located in places where surgery is difficult or impossible, no satisfactory treatment is available. 131MIBG is a combination of an adrenaline-like chemical and a radioactive form of iodine. The 131MIBG attaches to the tumor cells and the high concentration of radioactive iodine kills them. Previous studies using 131MIBG to treat pheochromocytoma had a 36% response rate in terms of complete or partial improvement. This study will examine whether adding other sensitization medications to the 131MIBG treatment regimen will enhance its effectiveness in reducing the size and number of tumors. Patients 18 years of age and older with malignant or inoperable pheochromocytoma may be eligible for this 18-month study. Candidates will be screened with various tests and procedures, which may include a medical history, physical examination, blood and urine tests, lung function studies, electrocardiogram, echocardiogram, computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and bone scans and other scans using radioactive MIBG and octreotide. Participants will be randomly assigned to one of two treatment groups: 1) 131MIBG plus sensitization medications, or 2) 131MIBG alone. All patients will be hospitalized 3 to 5 days for each 131MIBG treatment. The drug will be infused through a vein (intravenously, or I.V.) over 10 to 30 minutes. Patients will receive up to 3 treatments, separated by at least 3 months. All patients will also take potassium to protect the thyroid gland from radioactive iodine generated by the 131MIBG. The potassium is taken twice a day for 30 days, beginning the day before the 131MIBG treatment. Patients in the sensitization group will receive the following additional drugs for sensitization: methylprednisolone, intravenously a few minutes before 131MIBG treatment; Roaccutan, by mouth (capsules) twice a day for 6 weeks before treatment; Demser, by mouth 3 times a week for 1 week before treatment, and Carbidopa, by mouth every 6 hours for 4 days before treatment. After each treatment, patients will have a clinical evaluation and periodic blood tests to check for adverse side effects of radiotherapy. Follow-up visits at NIH will be scheduled at 12 and 18 months after the first 131MIBG treatment for clinical, laboratory and imaging tests. Patients who had tumors in the lungs before treatment will have lung function tests 1, 3, and 6 months after each treatment. CT, MRI 131MIBG, and PET scanning will be done 1 week before each treatment. Patients who have tumors that have grown by more than 25% and none that have shrunk by more than 50% or who have developed one or more new tumors while on 131MIBG treatment will be taken off the study.

Clinical Trial Conditions for DEMSER

Condition Name

Condition Name for DEMSER
Intervention	Trials
Autonomic Nervous System Diseases	1
Dopamine Beta-Hydroxylase Deficiency	1
Orthostatic Hypotension	1

Condition MeSH

Condition MeSH for DEMSER
Intervention	Trials
Nervous System Diseases	1
Psychotic Disorders	1
Hypotension, Orthostatic	1

Clinical Trial Locations for DEMSER

Trials by Country

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−

Trials by Country for DEMSER
Location	Trials
United States	3

Trials by US State

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−

Trials by US State for DEMSER
Location	Trials
New York	1
Tennessee	1
Maryland	1

Clinical Trial Progress for DEMSER

Clinical Trial Phase

Clinical Trial Phase for DEMSER
Clinical Trial Phase	Trials
Phase 3	1
Phase 2	2

Clinical Trial Status

Clinical Trial Status for DEMSER
Clinical Trial Phase	Trials
Completed	2
Terminated	1

Clinical Trial Sponsors for DEMSER

Sponsor Name

Sponsor Name for DEMSER
Sponsor	Trials
Valeant Pharmaceuticals International, Inc.	1
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)	1
Vanderbilt University	1

Sponsor Type

Sponsor Type for DEMSER
Sponsor	Trials
Industry	2
Other	2
NIH	1

Clinical Trials, Market Analysis, and Projections for Demser (Metyrosine)

Introduction to Demser

Demser, also known as metyrosine, is a tyrosine hydroxylase inhibitor used primarily for the treatment of pheochromocytoma, a neuroendocrine tumor that leads to excessive secretion of catecholamines such as norepinephrine and epinephrine. Here, we will delve into the clinical trials, market analysis, and future projections for Demser.

Clinical Trials and Approval

Demser received manufacturing and marketing approval in Japan in January 2019 for the improvement of catecholamine excess secretion in patients with pheochromocytoma. This approval was granted after the drug was designated as an orphan drug by the Ministry of Health, Labour and Welfare (MHLW) in May 2015[1].

Efficacy and Safety

Clinical studies have shown that Demser effectively reduces catecholamine biosynthesis in patients with pheochromocytoma. Administration of 1 to 4 grams of Demser per day can reduce catecholamine biosynthesis by 35% to 80%, as measured by the total excretion of catecholamines and their metabolites. The maximum biochemical effect typically occurs within two to three days, and the urinary concentration of catecholamines and their metabolites returns to pretreatment levels within three to four days after discontinuation[3][5].

Patient Response

Most patients treated with Demser experience a decrease in the frequency and severity of hypertensive attacks, along with associated symptoms such as headache, nausea, sweating, and tachycardia. Blood pressure decreases progressively during the first two days of therapy and increases gradually to pretreatment values within two to three days after withdrawal[5].

Market Analysis

Current Market Status

The approval and marketing of Demser in Japan mark a significant milestone in the treatment of pheochromocytoma. Given its orphan drug designation, Demser addresses a high medical need for patients who cannot sufficiently control their symptoms with sympatholytic drugs[1].

Market Size and Growth

While specific market size data for Demser is not readily available, the broader context of the clinical trials market provides insight into the potential growth. The U.S. clinical trials market, for instance, was valued at USD 25.81 billion in 2023 and is expected to grow to USD 41.57 billion by 2033. This growth is driven by ongoing research efforts and the need for innovative healthcare solutions[4].

Competitive Landscape

Demser operates in a niche market focused on rare diseases. The orphan drug designation and exclusive rights to develop and commercialize metyrosine in Japan, secured by Ono Pharmaceutical Co., Ltd. through a license agreement with Bausch Health Companies Inc., position Demser as a unique treatment option in this space[1].

Projections and Future Outlook

Market Expansion

Given the limited number of treatments available for pheochromocytoma, Demser is poised for significant market expansion. As more patients are diagnosed and treated, the demand for effective therapies like Demser is likely to increase.

Research and Development

Future research may focus on expanding the use of Demser to other conditions related to catecholamine excess. Additionally, ongoing clinical trials and observational studies could provide more insights into the long-term efficacy and safety of Demser, which is currently limited by the relatively small number of patients studied long-term[5].

Regulatory Environment

The regulatory environment, particularly the support from health authorities like the MHLW in Japan, is crucial for the continued development and marketing of Demser. Regulatory approvals and designations can significantly impact the drug's market accessibility and adoption[1].

Challenges and Considerations

Limited Long-Term Data

One of the significant challenges for Demser is the limited long-term data on its use. Clinical studies have not included sufficient numbers of subjects aged 65 and over, and chronic animal studies have not been conducted. This lack of data necessitates careful monitoring and periodic laboratory tests for patients requiring prolonged use of Demser[3][5].

Side Effects and Safety Monitoring

Demser's safety profile requires vigilant monitoring, especially in patients with impaired hepatic or renal function. The drug's effects on pregnancy and fertility have also not been fully studied, which may impact its use in certain patient populations[5].

Key Takeaways

• Approval and Efficacy: Demser received approval in Japan for treating pheochromocytoma and has shown significant efficacy in reducing catecholamine biosynthesis.
• Market Potential: The drug operates in a niche market with potential for expansion due to its unique treatment profile.
• Research Needs: There is a need for more long-term data and studies on Demser’s safety and efficacy in various patient populations.
• Regulatory Support: Continued regulatory support is crucial for the drug’s market success.
• Challenges: Limited long-term data and potential side effects require careful patient monitoring.

FAQs

What is Demser used for?

Demser (metyrosine) is used for the treatment of pheochromocytoma, a neuroendocrine tumor that leads to excessive secretion of catecholamines.

How does Demser work?

Demser inhibits tyrosine hydroxylase, the enzyme responsible for the first step in catecholamine biosynthesis, thereby reducing the production of catecholamines.

What are the common side effects of Demser?

Common side effects include decreased frequency and severity of hypertensive attacks, along with associated symptoms such as headache, nausea, sweating, and tachycardia.

Is Demser approved for use in all countries?

Demser has received manufacturing and marketing approval in Japan but may not be approved or widely available in other countries.

What are the long-term implications of using Demser?

Long-term use of Demser requires careful monitoring due to limited data on its long-term effects, particularly in older patients and those with impaired hepatic or renal function.

Sources

1. ONO Receives Manufacturing and Marketing Approval in Japan for Demser® Capsule - ONO Pharmaceutical Co., Ltd.
2. Alzheimer's Drug Development Pipeline: Positive Results, New Insight Position 2024 - UNLV
3. Demser: Package Insert / Prescribing Information - Drugs.com
4. U.S. Clinical Trials Market Size Industry Analysis Report, 2033 - Biospace
5. Demser (Metyrosine): Side Effects, Uses, Dosage, Interactions - RxList