Setmelanotide

Setmelanotide (Imcivree)

Evidence & Status

  • FDA Approved
  • Strong Human Evidence
  • Strong

FDA Approval Scope

Current U.S. labeling: POMC, PCSK1, or LEPR deficiency and Bardet-Biedl syndrome for patients age 2 years and older; acquired hypothalamic obesity for patients age 4 years and older.

At a Glance

A cyclic octapeptide MC4R agonist with label-specific U.S. indications and age boundaries.

Plain English

Setmelanotide is used only within its current product-label scope; it is not a general treatment for common or polygenic obesity.

Overview

A cyclic octapeptide MC4R agonist. Current U.S. labeling includes POMC, PCSK1, or LEPR deficiency and Bardet-Biedl syndrome for patients age 2 years and older, and acquired hypothalamic obesity for patients age 4 years and older. This record does not generalize those indications to common or polygenic obesity.

Research Summary

Direct Phase 3 human evidence includes POMC/PCSK1/LEPR-deficiency obesity and Bardet-Biedl syndrome populations. Administration, pharmacokinetics, and safety remain product- and label-specific.

Research Areas

  • Genetic & hypothalamic obesity (POMC/PCSK1/LEPR deficiency, BBS, acquired HO)
  • MC4R pathway physiology
  • Hypothalamic obesity
  • Melanocortin signaling

Safety & Risks

Serious Risks

  • Depression and suicidal ideation have occurred; monitor for new or worsening depression, suicidal thoughts, or suicidal behavior
  • Serious hypersensitivity reactions, including anaphylaxis, have been reported; prior serious hypersensitivity to setmelanotide or IMCIVREE excipients is a formal contraindication
  • Generalized skin hyperpigmentation, darkening of existing nevi, and development of new melanocytic nevi can occur; full-body skin examination is recommended before treatment and periodically during treatment
  • Spontaneous penile erections and other sexual adverse effects can occur; erections lasting longer than 4 hours require urgent medical attention
  • Patients with acquired hypothalamic obesity require monitoring for acute adrenal insufficiency
  • Patients with acquired hypothalamic obesity and central diabetes insipidus require monitoring for sodium imbalance, including hyponatremia and hypernatremia

Reported Side Effects

  • Skin hyperpigmentation
  • Injection site reactions
  • Nausea
  • Headache
  • Diarrhea
  • Abdominal pain
  • Vomiting
  • Depression
  • Spontaneous penile erection
United States
FDA-approved only for current labeled indications; not generalized to common or polygenic obesity.
United Kingdom
EMA-approved
Australia
TGA-approved
Canada
Health Canada-approved

Citations & Sources