Setmelanotide for Obesity

Recruiting at 12 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Rhythm Pharmaceuticals, Inc.

Must be taking: Setmelanotide

Disqualifiers: Melanoma, Depression, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Long-term

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This is an open-label extension study designed to evaluate the long-term safety and tolerability of continued setmelanotide treatment in male and female patients ≥2 years of age who have completed or transitioned from a previous study with setmelanotide for rare genetic, syndromic, or acquired diseases of obesity upstream of the MC4R pathway.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What data supports the effectiveness of the drug Setmelanotide for obesity?

Setmelanotide has been shown to cause significant weight loss, with at least a 10% decrease in body weight after one year, and reduced appetite in clinical trials for patients with specific genetic conditions causing obesity. It is approved for use in children and adults with these genetic disorders, demonstrating its effectiveness in managing obesity linked to these conditions. ^{1 2 3 4 5}

Is setmelanotide safe for humans?

Setmelanotide has been tested in clinical trials and is generally considered safe for humans, but it can cause side effects like injection site reactions, skin darkening, nausea, headaches, and diarrhea. No major side effects were observed in a study with a 5-year-old child, except for skin darkening and temporary spontaneous erections. ^{1 2 3 4 6}

How is the drug setmelanotide different from other obesity treatments?

Setmelanotide is unique because it specifically targets and activates the melanocortin-4 receptor (MC4R), which is involved in regulating hunger and body weight, making it effective for obesity caused by rare genetic conditions like POMC, PCSK1, and LEPR deficiencies. Unlike other treatments, it is a daily injection and is the first FDA-approved drug for these specific genetic forms of obesity. ^{1 2 3 4 7}

Research Team

David Meeker, MD

Principal Investigator

Rhythm Pharmaceuticals, Inc.

Eligibility Criteria

This trial is for males and females aged 2 years or older who have obesity due to rare genetic, syndromic, or acquired conditions affecting the MC4R pathway. Participants must have previously completed or transitioned from a setmelanotide study.

Inclusion Criteria

Agree to use a highly effective form of contraception and follow the study contraception requirements throughout study duration and for 90 days after

Demonstrated clinical benefit in the previous setmelanotide study, as determined by the Investigator

I am over 2 years old and have previously participated in a setmelanotide study.

Exclusion Criteria

Pregnant and/or breastfeeding women

I have experienced new or worsening depression with suicidal thoughts or behaviors.

Discontinuation from a previous setmelanotide study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive once daily subcutaneous injections of setmelanotide

Long-term

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Setmelanotide

Trial Overview The trial is testing the long-term safety and effectiveness of continued treatment with Setmelanotide, a medication aimed at treating obesity by targeting specific pathways related to weight regulation.

Participant Groups

Group I: Setelanotide (Open-label) Experimental Treatment 1 Intervention

Once daily (QD) subcutaneous injection of setmelanotide

Who Is Running the Clinical Trial?

Rhythm Pharmaceuticals, Inc.

Lead Sponsor

Trials

31

Recruited

10,400+

Findings from Research

Setmelanotide is an MC4 receptor agonist approved in the USA for chronic weight management in patients aged 6 and older with obesity due to POMC, PCSK1, or LEPR deficiencies, highlighting its targeted efficacy for specific genetic causes of obesity.

The drug has also received PRIME designation from the European Medicines Agency, indicating its potential for treating obesity and hunger control in various rare genetic disorders linked to the MC4 receptor pathway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Setmelanotide: First Approval. Markham, A.[2021]

Setmelanotide is an FDA-approved injectable drug that significantly aids in weight loss, showing at least a 10% decrease in body weight after one year in patients with specific genetic forms of obesity, based on data from multiple clinical trials.

Common side effects include injection site reactions, skin hyperpigmentation, nausea, headache, and diarrhea, indicating that while effective, patients may experience notable adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Setmelanotide: A Novel Targeted Treatment for Monogenic Obesity. Pressley, H., Cornelio, CK., Adams, EN.[2023]

Setmelanotide significantly aids in weight loss for patients with severe obesity linked to MC4R deficiency, with an average weight loss of 6.91% over a mean follow-up of 52 weeks among 328 patients.

While effective for weight loss, setmelanotide is associated with an increased risk of skin hyperpigmentation, indicating a need for monitoring side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Setmelanotide, a Melanocortin-4 Receptor Agonist, for Obese Patients: A Systematic Review and Meta-Analysis. Ferraz Barbosa, B., Aquino de Moraes, FC., Bordignon Barbosa, C., et al.[2023]

Setmelanotide, a melanocortin-4 receptor activator, has led to significant weight loss in two patients with pro-opiomelanocortin deficiency, a rare condition causing severe obesity.

While setmelanotide shows promise for treating obesity, caution is advised due to its potential effects on other melanocortin receptors, which could lead to unintended consequences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic Precision Medicines: Curing POMC Deficiency. Müller, TD., Tschöp, MH., O'Rahilly, S.[2022]

Setmelanotide has been approved for treating specific genetic conditions that cause obesity, representing a significant step in personalized medicine for obesity management.

Semaglutide, which has shown to produce approximately twice the weight loss compared to older antiobesity medications, is under regulatory review for treating obesity and is already used for diabetes, highlighting its dual efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Next Generation Antiobesity Medications: Setmelanotide, Semaglutide, Tirzepatide and Bimagrumab: What do They Mean for Clinical Practice? Ryan, DH.[2021]

Setmelanotide, a melanocortin-4 receptor agonist, led to significant weight loss of 30 kg (36% of body weight) in a 5-year-old child with obesity due to POMC deficiency after 12 months of treatment, demonstrating its efficacy in managing genetic obesity.

The treatment not only improved the child's hyperphagia and metabolic status but also positively impacted the quality of life for the parents, highlighting the broader benefits of early intervention with setmelanotide in young children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beneficial Effects of Setmelanotide in a 5-Year-Old Boy With POMC Deficiency and on His Caregivers. Dubern, B., Lourdelle, A., Clément, K.[2023]

Setmelanotide is a potent MC4R agonist that effectively promotes weight loss in obese individuals with MC4R deficiency, as demonstrated in a 28-day Phase 1b clinical trial.

The drug showed greater efficacy in patients with POMC defects compared to those with MC4R mutations, indicating that while Setmelanotide can aid weight loss in MC4R deficiency, further research is needed to determine its effectiveness across different genetic backgrounds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of a melanocortin-4 receptor (MC4R) agonist (Setmelanotide) in MC4R deficiency. Collet, TH., Dubern, B., Mokrosinski, J., et al.[2022]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Setmelanotide: First Approval. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Setmelanotide: A Novel Targeted Treatment for Monogenic Obesity. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Setmelanotide, a Melanocortin-4 Receptor Agonist, for Obese Patients: A Systematic Review and Meta-Analysis. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Metabolic Precision Medicines: Curing POMC Deficiency. [2022]

5. Korea (South) pubmed.ncbi.nlm.nih.gov

Next Generation Antiobesity Medications: Setmelanotide, Semaglutide, Tirzepatide and Bimagrumab: What do They Mean for Clinical Practice? [2021]

6. England pubmed.ncbi.nlm.nih.gov

Beneficial Effects of Setmelanotide in a 5-Year-Old Boy With POMC Deficiency and on His Caregivers. [2023]

7. Germany pubmed.ncbi.nlm.nih.gov

Evaluation of a melanocortin-4 receptor (MC4R) agonist (Setmelanotide) in MC4R deficiency. [2022]