Setmelanotide for Obesity

Recruiting at 56 trial locations

Overseen By Daniel Mogford

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Rhythm Pharmaceuticals, Inc.

Disqualifiers: Psychiatric disorders, Suicidal ideation, Pulmonary, Cardiac, Endocrine, 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: 12 weeks

400 Participants Needed

Trial Summary

What is the purpose of this trial?

The protocol describes a randomized, double-blind, placebo-controlled trial with independent sub-studies of setmelanotide in patients with obesity and at least one of the specific gene variants in the Melanocortin-4 Receptor pathway: * POMC or PCSK1 (Sub-study 035a) * LEPR (Sub-study 035b) * SRC1 (Sub-study 035c) * SH2B1 (Sub-study 035d) The objectives and endpoints are identical for these sub-studies.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, it excludes participants with certain health conditions and those who have recently participated in other clinical studies, which might imply some restrictions. Please consult with the trial coordinators for specific guidance.

Do I need to stop my current medications to join the trial?

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

What data supports the idea that Setmelanotide for Obesity is an effective drug?

The available research shows that Setmelanotide is effective for treating obesity caused by specific genetic conditions. In clinical trials, patients experienced significant weight loss, with at least a 10% decrease in body weight after one year. It also helped reduce appetite. Setmelanotide is the first FDA-approved drug for obesity related to certain genetic deficiencies, making it a unique option for those conditions. Compared to other drugs like semaglutide, which is also used for obesity, Setmelanotide is specifically targeted for rare genetic causes of obesity. ^{1 2 3 4 5}

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

Setmelanotide has been shown to help people with certain genetic conditions lose weight, with studies showing at least a 10% decrease in body weight after one year and reduced appetite. It is approved for use in children and adults with specific genetic causes of obesity, and has demonstrated significant weight loss in clinical trials. ^{1 2 3 4 5}

What safety data is available for Setmelanotide in treating obesity?

Setmelanotide has been evaluated in several clinical trials, including two phase 2, two phase 3, and one ongoing trial. Common adverse effects reported include injection site reactions (96%), skin hyperpigmentation (78%), nausea (56%), headache (41%), and diarrhea (37%). In a case study of a 5-year-old with POMC deficiency, no major side effects were observed except for hyperpigmentation and transient spontaneous erections. Overall, Setmelanotide is considered effective for treating obesity in patients with specific genetic disorders, but it may have side effects that need to be monitored. ^{1 2 3 4 6}

Is setmelanotide safe for treating obesity?

Setmelanotide is generally safe for treating obesity, but common side effects include reactions at the injection site, skin darkening, nausea, headache, and diarrhea. In a study with a 5-year-old, no major side effects were observed, except for skin darkening and temporary spontaneous erections. ^{1 2 3 4 6}

Is the drug Setmelanotide a promising treatment for obesity?

Yes, Setmelanotide is a promising drug for treating obesity, especially in people with certain genetic conditions. It helps reduce weight and control hunger by targeting specific pathways in the body. It has shown significant weight loss in clinical trials and is approved for use in both children and adults with these genetic disorders. ^{1 2 3 4 7}

How is the drug Setmelanotide unique in treating obesity?

Setmelanotide is unique because it specifically targets and activates the melanocortin-4 receptor (MC4R), which is involved in regulating body weight, and is the first FDA-approved drug for treating obesity caused by specific genetic deficiencies like POMC, PCSK1, and LEPR. It is administered as a daily injection and is particularly effective for individuals with these rare genetic conditions. ^{1 2 3 4 7}

Research Team

David Meeker, MD

Principal Investigator

Rhythm Pharmaceuticals, Inc.

Eligibility Criteria

This trial is for people aged 6-65 with obesity and specific genetic variants affecting the MC4R pathway. They should have tried diet and exercise, experienced childhood obesity, and not be pregnant or breastfeeding. Exclusions include recent bariatric surgery, severe psychiatric or medical conditions, a history of melanoma or certain skin lesions, significant weight loss recently, or participation in other drug trials within the last three months.

Inclusion Criteria

Patient and/or parent or guardian must be able to understand and comply with the requirements of the study and must be able to understand and sign the written informed consent/assent

My genetic test shows a variant in the NCOA1 gene.

I have a genetic variant in the POMC or PCSK1 gene.

Exclusion Criteria

I or my immediate family have a history of melanoma, or I have oculocutaneous albinism.

I have had weight loss surgery recently.

Patients with glycated hemoglobin (HbA1C) >10% at Screening

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive setmelanotide or placebo in a double-blind, randomized manner

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Setmelanotide

Trial Overview The EMANATE trial is testing Setmelanotide against a placebo to see if it helps with weight loss in patients who have certain gene variants linked to obesity. It's randomized (participants are put into groups by chance), double-blind (neither participants nor researchers know who gets what treatment), and has identical goals across different sub-studies focusing on various genes.

Participant Groups

Group I: SH2B1 variant Experimental Treatment 2 Interventions

1:1 Randomization

Group II: POMC or PCSK1 variant Experimental Treatment 2 Interventions

1:1 Randomization

Group III: NCOA1 (SRC1) variant Experimental Treatment 2 Interventions

1:1 Randomization

Group IV: LEPR variant Experimental Treatment 2 Interventions

1:1 Randomization

Setmelanotide is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Imcivree for:

• Chronic weight management in adult and pediatric patients 6 years of age and older with obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS).

Approved in European Union as Imcivree for:

• Chronic weight management in adult and pediatric patients 6 years of age and older with obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS).

Approved in Canada as Imcivree for:

• Chronic weight management in adult and pediatric patients 6 years of age and older with obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS).

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]