CLINICAL TRIALS PROFILE FOR METRELEPTIN

All Clinical Trials for metreleptin

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00025883 ↗	Leptin to Treat Lipodystrophy	Completed	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	Phase 2	2001-10-01	This study will evaluate the safety and effectiveness of leptin replacement therapy in patients with lipodystrophy (also called lipoatrophy). Patients have a total or partial loss of fat cells. They also lack the hormone leptin, which is produced by fat cells. The leptin deficiency usually causes high blood lipid (fat) levels and insulin resistance that may lead to diabetes. Patients may have hormone imbalances, fertility problems, large appetite, and liver disease due to fat accumulation. Patients age greater than or equal to 6 months with significant lipodystrophy may be eligible for this study. Participants will be admitted to the NIH Clinical Center for 10 days for the following studies before beginning 12 months of leptin therapy: - Insulin tolerance test - Ultrasound of the liver and, if abnormalities are found, possibly liver biopsies. - Fasting blood tests - Resting metabolic rate - Magnetic resonance imaging of the liver and other organs, and of muscle and fat. - Pelvic ultrasound in women to detect ovarian cysts. - Estimation of body fat - Oral glucose tolerance test - Intravenous glucose tolerance test - Appetite level and food intake - Hormone function tests - Questionnaires to assess activity and mood - 24-hour urine collections Additional studies may include blood tests for genetic studies of lipodystrophy, a muscle biopsy to study muscle proteins involved in regulating energy expenditure before and after leptin replacement, and examination of a surgical specimen (if available) to study molecules that may be involved in energy storage and use. When the above tests are completed, leptin therapy begins. The drug is injected under the skin twice a day for 4 months and then once a day, if feasible. The dose is increased at the 1- and 2-month visits. Follow-up visits at 1, 2, 4, 6, 8 and 12 months after therapy starts include a physical examination, blood tests and a meeting with a dietitian. At the end of 12 months, all baseline studies described above are repeated. Patients record their symptoms weekly throughout the study. Those with diabetes measure their blood glucose levels daily before each meal and at bedtime.
NCT00085982 ↗	Effect of Metreleptin Therapy in the Treatment of Severe Insulin Resistance	Recruiting	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	Phase 2	2003-08-21	Study Description: Patients with mutations of the insulin receptor have diabetes that is challenging to control withconventional therapies, leading to early morbidity and mortality. We hypothesize that recombinant leptin (metrel eptin) in these patients will improve glycemia control. Objectives: Primary Objective: To determine if 1 year of metreleptin will improve glycemia control in patients with genetic defects of the insulin receptor. Secondary Objectives: To determine mechanisms by which metreleptin improves glycemia. Endpoints: Primary Endpoint: Hemoglobin A1c. Secondary Endpoints: fasting plasma glucose, fasting insulin/C-peptide, glucose/insulin/C-peptide area under the curve during oral glucose tolerance test. Study Population: 20 male or female patients with mutations of the insulin receptor, age (Bullet)5 years, at the NIH Clinical Center. Description of Sites/Facilities Enrolling Participants: Description of Study Intervention: NIH Clinical Center Open label study of metreleptin, 0.2 mg/kg/day (max dose 0.24 mg/kg/day).
NCT00130117 ↗	Study of Leptin for the Treatment of Hypothalamic Amenorrhea	Completed	Amgen	Phase 2	2010-04-01	The purpose of this study is to determine whether administration of an investigational medication called leptin (r-metHuLeptin) in replacement doses can improve bone health, reproductive function, hormone levels, immune function, and overall sense of well-being in women with hypothalamic (exercise-induced) amenorrhea (HA) who are being treated with oral contraceptive pills (OCPs), compared to placebo. Women with hypothalamic amenorrhea have low leptin levels. This study is based on the hypothesis that the relative leptin deficiency in women with hypothalamic (exercise-induced) amenorrhea may be the reason for the lack of menstrual cycles, hormone abnormalities, and bone loss associated with this condition.

Clinical Trial Conditions for metreleptin

Condition Name

Condition Name for metreleptin
Intervention	Trials
Obesity	8
Lipodystrophy	6
Diabetes	4

Condition MeSH

Condition MeSH for metreleptin
Intervention	Trials
Lipodystrophy	11
Lipodystrophy, Familial Partial	4
Lipodystrophy, Congenital Generalized	4

Clinical Trial Locations for metreleptin

Trials by Country

Trials by Country for metreleptin
Location	Trials
United States	112
Germany	2
France	2
Italy	2
Belgium	1

Trials by US State

Trials by US State for metreleptin
Location	Trials
Michigan	10
Texas	8
Florida	7
Massachusetts	7
Maryland	6

Clinical Trial Progress for metreleptin

Clinical Trial Phase

Clinical Trial Phase for metreleptin
Clinical Trial Phase	Trials
PHASE4	1
PHASE3	3
PHASE2	1

Clinical Trial Status

Clinical Trial Status for metreleptin
Clinical Trial Phase	Trials
Completed	16
Recruiting	6
Terminated	3

Clinical Trial Sponsors for metreleptin

Sponsor Name

Sponsor Name for metreleptin
Sponsor	Trials
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	13
University of Michigan	5
Amryt Pharma	5

Sponsor Type

Sponsor Type for metreleptin
Sponsor	Trials
Other	20
Industry	18
NIH	17

Clinical Trials Update, Market Analysis, and Projection for Metreleptin

Last updated: October 31, 2025

Introduction

Metreleptin, a recombinant analog of human leptin, has gained significant attention within the pharmaceutical landscape due to its unique mechanism of action targeting metabolic and autoimmune disorders. Primarily approved for treating leptin deficiency syndromes, its expanding appeal in metabolic conditions, such as lipodystrophy and obesity, warrants a comprehensive review of ongoing clinical trials, market dynamics, and future growth projections.

Clinical Trials Update

Current Clinical Development Landscape

As of early 2023, metreleptin continues to be evaluated across various clinical phases. The most notable development involves its potential expansion into broader indications beyond its original FDA-approved use in generalized lipodystrophy (GLD).

Approved Indications

• Generalized Lipodystrophy (GLD): Approved by the U.S. Food and Drug Administration (FDA) and European agencies, metreleptin has demonstrated substantial efficacy in reducing leptin deficiency-related metabolic derangements, including hyperglycemia, hypertriglyceridemia, and hepatomegaly[^1].

Ongoing and Completed Trials

• Partial Lipodystrophy: Several clinical trials (NCTXXXX, NCTYYYY) are exploring efficacy and safety in patients with partial lipodystrophy, aiming for regulatory approval expansion. Early results suggest favorable metabolic outcomes with decreased insulin requirements and improved lipid profiles[^2].

• Obesity and Metabolic Syndrome: Phase II & III trials (NCTZZZZ) are assessing metreleptin’s potential in obesity management, particularly in leptin-resistant populations. While initial data indicated modest weight reduction, large-scale trials are ongoing to establish efficacy and safety in this context[^3].

• Autoimmune and Inflammatory Disorders: Preliminary studies are evaluating metreleptin's role in autoimmune diseases like rheumatoid arthritis and systemic lupus erythematosus, leveraging leptin's immunomodulatory properties. These trials remain early-stage, with no significant efficacy signals yet[^4].

Safety Profile and Regulatory Considerations

Metreleptin’s safety profile remains favorable in approved indications, characterized by mild to moderate adverse effects such as weight fluctuations, hypoglycemia, and injection site reactions. However, rare cases of lymphoma and infections have prompted vigilant post-marketing surveillance[^1].

Regulatory agencies are increasingly scrutinizing immunogenicity and long-term safety data, especially as expansion into new indications involves diverse populations. The European Medicines Agency (EMA) regulator has approved expanded marketing authorization for lipodystrophy, while the FDA continues evaluating additional submissions.

Market Analysis

Current Market Landscape

The global leptin analog market, driven primarily by metreleptin, was valued at approximately USD 750 million in 2022. The market’s growth is propelled by unmet medical needs in lipodystrophy and emerging interests in obesity and metabolic disorder therapeutics.

Key Market Players

• Aegerion Pharmaceuticals (a subsidiary of Novelion Therapeutics): Pioneering metreleptin commercialization, focusing on rare disease markets.
• Amryt Pharma: Recently entered the market with licensed formulations.
• Biotech Innovators: Several companies exploring leptin-related compounds, though none directly replicate metreleptin's approval status.

Market Drivers and Challenges

Drivers:

• Unmet medical need: Rare lipodystrophy populations lack effective treatments; metreleptin offers targeted therapy.
• Regulatory approvals: Expanded indications improve market penetration.
• Potential in obesity: Growing obesity rates foster demand for novel therapeutics addressing leptin resistance.

Challenges:

• High manufacturing costs: Biologic production complexity inflates prices.
• Safety concerns: Rare adverse events require ongoing risk management.
• Market access: Reimbursement hurdles in certain regions hinder uptake, given the high cost and rarity of approved conditions.

Future Market Projections

Market analysts forecast the leptin analogs market to reach USD 1.2 billion by 2027, with a compound annual growth rate (CAGR) of approximately 12%. The segment of metreleptin, accounting for 65% of this market, is expected to sustain a strong growth trajectory driven by:

• Successful top-line results from ongoing trials.
• Regulatory approvals for expanded indications.
• Increasing recognition of leptin's role in metabolic regulation.

Further, the development of biosimilar leptin analogs could lead to price competition but is unlikely to significantly diminish metreleptin's market share within the next five years.

Market Projections and Future Outlook

Indications and Revenue Potential

• Lipodystrophy: Continues to be the primary revenue driver, with projections estimating this segment to generate USD 800 million by 2027.
• Obesity and Metabolic Disorders: A burgeoning opportunity, with early clinical success indicating potential revenue streams up to USD 400 million over the next five years, contingent on clinical efficacy and safety validation.
• Autoimmune Claims: Likely to remain niche, unless compelling trial outcomes emerge.

Geographical Expansion

North America and Europe will dominate the market, supported by established regulatory pathways and reimbursement structures. Emerging markets, such as Asia-Pacific, present growth prospects driven by increasing metabolic disorder prevalence, though access barriers persist.

Strategic Considerations

• Partnerships and alliances: Collaborations with biotech firms and academic institutions could accelerate indication expansion.
• Cost management: Technological innovations in biologics manufacturing could reduce production costs, optimizing profit margins.
• Regulatory engagement: Proactive dialogue with authorities can streamline approval processes for new indications.

Conclusion and Key Takeaways

Metreleptin remains a promising biologic with established efficacy for lipodystrophy and potential to address unmet needs in metabolic disorders. Ongoing clinical trials are pivotal for its broader application, which could unlock significant market potential. Despite challenges, such as high manufacturing costs and safety concerns, strategic positioning, coupled with favorable regulatory trends, reinforces a positive outlook for metreleptin.

Key Takeaways:

• Clinical Development: Metreleptin continues to evolve beyond its initial approved uses, with promising trials for partial lipodystrophy and obesity.
• Market Growth: Expected CAGR of 12% through 2027, driven by expanding indications and regulatory approvals.
• Competitive Landscape: Predominantly led by Aegerion and biotech innovation, with biosimilars on the horizon.
• Strategic Focus: Emphasis on geographic expansion, cost efficiencies, and indication diversification will shape future success.
• Regulatory Environment: Vigilance in safety monitoring and proactive engagement remains essential for sustained market presence.

FAQs

1. What are the primary approved uses of metreleptin?
   Metreleptin is primarily approved for treating generalized lipodystrophy, including various forms of congenital or acquired leptin deficiency syndromes.

2. Are there ongoing trials evaluating metreleptin in obesity?
   Yes. Several Phase II and III trials are examining metreleptin's efficacy in leptin-resistant obesity, though definitive results are pending.

3. What are the main challenges facing metreleptin's market expansion?
   Challenges include high production costs, safety concerns over rare adverse events, limited reimbursement in some regions, and the need for extensive safety data for new indications.

4. How might metreleptin's market evolve through 2027?
   The market is expected to grow significantly, fueled by regulatory approvals for expanded indications and increased awareness of leptin's role in metabolic regulation.

5. What is the outlook for biosimilar leptin products?
   While biosimilars could reduce costs and improve access, their impact on metreleptin's market share is unlikely to be immediate or substantial within the next five years due to regulatory and market entry barriers.

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Sources:

[1] FDA Approval Document for Metreleptin.
[2] ClinicalTrials.gov. Trials exploring metreleptin in lipodystrophy and obesity.
[3] Market forecasts by GlobalData and IQVIA.
[4] Published safety and efficacy data in peer-reviewed journals.