Setmelanotide for Obesity

Enrolling by invitation 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the long-term safety of setmelanotide, a treatment for rare forms of obesity linked to specific genetic conditions affecting the MC4R pathway, which helps regulate body weight. Participants will receive a daily injection to evaluate the treatment's effectiveness over time. Ideal candidates are those who completed a previous study with setmelanotide and found it beneficial for their condition. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to the potential availability of this treatment.

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.

Is there any evidence suggesting that setmelanotide is likely to be safe for humans?

Research has shown that setmelanotide is generally safe for patients. Studies have found it can lead to significant weight loss and better hunger control. The FDA has already approved this medication for certain obesity-related conditions, indicating its safety for those uses.

In past studies, patients, including young children, used setmelanotide for up to a year and experienced meaningful weight loss without major safety concerns. While all treatments can have side effects, current data suggests that setmelanotide is safe enough for further study in clinical trials. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Setmelanotide is unique because it targets specific genetic causes of obesity by activating the melanocortin-4 receptor (MC4R), a mechanism not used by existing treatments. Most current options for obesity, such as lifestyle changes or medications like orlistat and phentermine, focus on reducing appetite or absorption of fat without addressing genetic factors directly. Researchers are excited about setmelanotide because it offers a targeted approach for those whose obesity is driven by genetic conditions, potentially providing a more effective solution for a subgroup of patients who don't respond well to traditional treatments. Additionally, it is administered via a once-daily subcutaneous injection, which could offer a convenient option for long-term management.

What evidence suggests that setmelanotide might be an effective treatment for obesity?

Research has shown that setmelanotide, which participants in this trial will receive, aids in weight loss, particularly for those with rare genetic types of obesity. Studies have found that setmelanotide leads to significant weight loss and reduces hunger. For example, one patient with a specific type of obesity lowered their BMI (body mass index, a measure of body fat based on height and weight) by nearly 15% after six months of treatment. Another study found that many participants lost at least 5 kilograms or 5% of their body weight. Overall, setmelanotide has demonstrated promising results in helping patients with certain obesity conditions lose weight. ^{1 4 6 7 8}

Who Is on the Research Team?

David Meeker, MD

Principal Investigator

Rhythm Pharmaceuticals, Inc.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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, 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 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10608339/

Efficacy and Safety of Setmelanotide, a Melanocortin-4 ... Our results show that setmelanotide (MC4R agonist) is associated with significant weight loss, body measurement, and hunger improvements in individuals who ...

2. ir.rhythmtx.com ir.rhythmtx.com/news-releases/news-release-details/rhythm-pharmaceuticals-announces-new-data-presentations-patients

Release Details One adult patient with congenital hypothalamic obesity achieved a -14.8% BMI reduction baseline at month 6 of setmelanotide therapy.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02896192

NCT02896192 | Setmelanotide for the Treatment of Early- ... Participants who achieved at least a 5 kilograms (kg) weight loss (or at least 5% weight loss if baseline body weight was <100 kg) at the end of the open label ...

4. firstwordpharma.com firstwordpharma.com/story/6523681

Rhythm Pharmaceuticals Announces Presentation of Four ... Phase 3 TRANSCEND trial data showed setmelanotide achieved significant BMI reductions in patients with acquired hypothalamic obesity on ...

5. imcivree.com imcivree.com/hcp/bbs/adults/

BBS in Adults | IMCIVREE® (setmelanotide) injection | For ... In patients ≥18 years of age with obesity due to BBS, IMCIVREE® delivered early, significant, and sustained weight reduction. Please see full Prescribing ...

6. imcivree.com imcivree.com/

IMCIVREE® (setmelanotide) injection IMCIVREE is the first and only FDA-approved treatment to target the impaired MC4R pathway, a root cause of obesity and hunger in people living with Bardet-Biedl ...

7. ir.rhythmtx.com ir.rhythmtx.com/news-releases/news-release-details/rhythm-pharmaceuticals-presents-data-mc4r-agonists-setmelanotide

Rhythm Pharmaceuticals Presents Data on MC4R Agonists ... Rhythm Pharmaceuticals Presents Data on MC4R Agonists Setmelanotide and Bivamelagon at ENDO 2025 · -9.3% BMI reduction from baseline in the 600mg ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2213858724002730

Setmelanotide in patients aged 2–5 years with rare MC4R ... 52 weeks of treatment with the MC4R agonist setmelanotide was associated with meaningful reduction in age-appropriate weight-related measures in paediatric ...