Setmelanotide

Generic Name: Setmelanotide

Brand Names: Imcivree

Drug Type: Small Molecule

Chemical Formula: C_₄₉H_₆₈N_₁₈O_₉S_₂

CAS Number: 920014-72-8

Unique Ingredient Identifier: N7T15V1FUY

Background: Setmelanotide is the first available treatment for patients with pro-opiomelanocortin, proprotein subilisin/kexin type 1, or leptin deficiencies. It is an agonist of the melanocortin 4 receptor. Earlier attempts at agonizing MC4R (such as LY2112688) lead to successful weight loss, but also an increase in blood pressure and heart rate. Other earlier treatments for these patients included gastric bypass surgery. Patients taking setmelanotide experienced an average weight loss of 0.6 kg/week.

Imcivree was granted EMA orphan designation on November 19, 2018 and FDA approval on November 25, 2020. On May 4, 2023, it was approved by Health Canada.

Indication: Setmelanotide is indicated for chronic weight management in patients 6 years and older with obesity due to pro-opiomelanocortin (POMC) deficiency, proprotein subtilisin/kexin type 1 (PCSK1) deficiency, or leptin receptor (LEPR) deficiency as determined by an approved test demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance. These conditions affect the MC4R signalling pathway.

Setmelanotide is also indicated for chronic weight management in patients 6 years and older with obesity due to Bardet-Biedl syndrome.

The drug is not reported to be effective in patients with POMC, PCSK1, or LEPR variants classified as benign or likely benign, as well as other types of obesity not listed above.

Associated Conditions: Leptin Receptor Deficiency Obesity, Obesity, Pro-opiomelanocortin (POMC) Deficiency Obesity, Proprotein convertase subtilisin/kexin type 1 (PCSK1) deficiency obesity

Associated Therapies: Chronic Weight Management therapy

Clinical Trials

A Single-center Study of Setmelanotide in Patients With Prader-Willi Syndrome

Phase 2

Recruiting

Conditions: Prader-Willi Syndrome
Obesity
Hyperphagia

Interventions: Drug: Setmelanotide

First Posted Date: 2025-01-13

Last Posted Date: 2025-03-19

Lead Sponsor: Rhythm Pharmaceuticals, Inc.

Target Recruit Count: 20

Registration Number: NCT06772597

Locations: 🇺🇸
University of Florida, Gainesville, Florida, United States

A Trial of Setmelanotide in Patients With Congenital Hypothalamic Obesity (Sub-study of NCT05774756)

Phase 3

Not yet recruiting

Conditions: Hypothalamic Obesity
Multiple Pituitary Hormone Deficiency Genetic Form
Septo-Optic Dysplasia
Optic Nerve Hypoplasia
Childhood-onset Combined Pituitary Hormone Deficiency
Pituitary Stalk Interruption Syndrome

Interventions: Drug: Setmelanotide
Drug: Placebo

First Posted Date: 2025-01-07

Last Posted Date: 2025-03-21

Lead Sponsor: Rhythm Pharmaceuticals, Inc.

Target Recruit Count: 39

Registration Number: NCT06760546

Open-Label Extension Study of Setmelanotide

Phase 3

Conditions: Obesity Associated With Defects in Leptin-melanocortin Pathway

Interventions: Drug: Setmelanotide

First Posted Date: 2024-09-19

Last Posted Date: 2025-05-16

Lead Sponsor: Rhythm Pharmaceuticals, Inc.

Target Recruit Count: 30

Registration Number: NCT06596135

Locations: 🇺🇸
HonorHealth Research Institute, Scottsdale, Arizona, United States
🇺🇸
UC San Diego- Rady Children's Hospital, San Diego, California, United States
🇺🇸
University of Florida at Gainesville, Gainesville, Florida, United States

and more 10 locations

A Trial of Setmelanotide in Acquired Hypothalamic Obesity

Phase 3

Active, not recruiting

Conditions: Hypothalamic Obesity

Interventions: Drug: Placebo
Drug: Setmelanotide

First Posted Date: 2023-03-20

Last Posted Date: 2025-04-17

Lead Sponsor: Rhythm Pharmaceuticals, Inc.

Target Recruit Count: 120

Registration Number: NCT05774756

Locations: 🇬🇧
Birmingham Women and Children's Hospital NHS Trust, Birmingham, United Kingdom
🇺🇸
Ohio State Wexner Medical Center, Columbus, Ohio, United States
🇺🇸
Children's Hospital Colorado, Aurora, Colorado, United States

and more 25 locations

Phase 3 Crossover Trial of Two Formulations of Setmelanotide in Participants With Specific Gene Defects in the MC4R Pathway

Phase 3

Completed

Conditions: Bardet-Biedl Syndrome
POMC Deficiency

Interventions: Drug: Setmelanotide 20 mg
Drug: Setmelanotide 25 mg
Drug: Setmelanotide 30 mg
Drug: Setmelanotide 3 mg
Drug: Setmelanotide 2 mg
Drug: Setmelanotide 2.5 mg

First Posted Date: 2022-01-18

Last Posted Date: 2024-11-26

Lead Sponsor: Rhythm Pharmaceuticals, Inc.

Target Recruit Count: 19

Registration Number: NCT05194124

Locations: 🇵🇷
UPR Medical Sciences Campus, Rio Piedras, Puerto Rico
🇳🇱
Erasmus MC, Rotterdam, Netherlands
🇩🇪
Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany

and more 4 locations

EMANATE: A Study of Setmelanotide in Patients With Specific Gene Variants in the MC4R Pathway

Phase 3

Active, not recruiting

Conditions: Genetic Obesity
Obesity

Interventions: Drug: Setmelanotide
Drug: Placebo

First Posted Date: 2021-10-26

Last Posted Date: 2025-05-09

Lead Sponsor: Rhythm Pharmaceuticals, Inc.

Target Recruit Count: 400

Registration Number: NCT05093634

Locations: 🇺🇸
Phoenix Children's Hospital, Phoenix, Arizona, United States
🇺🇸
HonorHealth Bariatric Center, Scottsdale, Arizona, United States
🇺🇸
Children's Hospital Los Angeles, Los Angeles, California, United States

and more 53 locations

Study of Setmelanotide Effects on QTc (Corrected QT) Interval in Healthy Participants

Phase 4

Completed

Conditions: Healthy

Interventions: Drug: Moxifloxacin
Drug: Setmelanotide
Drug: Oral Placebo
Drug: SC Placebo

First Posted Date: 2021-09-16

Last Posted Date: 2024-05-03

Lead Sponsor: Rhythm Pharmaceuticals, Inc.

Target Recruit Count: 77

Registration Number: NCT05046132

Locations: 🇺🇸
Parexel Early Phase Clinical Unit (Los Angeles), Glendale, California, United States

Setmelanotide in Pediatric Participants With Rare Genetic Diseases of Obesity

Phase 3

Completed

Conditions: Bardet-Biedl Syndrome
PCSK1 Deficiency Obesity
LEPR Deficiency Obesity
POMC Deficiency Obesity

Interventions: Drug: Setmelanotide

First Posted Date: 2021-07-19

Last Posted Date: 2024-11-27

Lead Sponsor: Rhythm Pharmaceuticals, Inc.

Target Recruit Count: 12

Registration Number: NCT04966741

Locations: 🇺🇸
Columbia University Medical Center, Division of Pediatric Endocrinology, Diabetes and Metabolism, New York, New York, United States
🇺🇸
Children's Hospital Colorado, Aurora, Colorado, United States
🇬🇧
Addenbrooke's Hospital, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, United Kingdom

and more 3 locations

DAYBREAK: A Study of Setmelanotide in Participants With Specific Gene Variants in the Melanocortin-4 Receptor (MC4R) Pathway

Phase 2

Completed

Conditions: Genetic Obesity

Interventions: Drug: Setmelanotide
Drug: Placebo

First Posted Date: 2021-07-15

Last Posted Date: 2024-11-08

Lead Sponsor: Rhythm Pharmaceuticals, Inc.

Target Recruit Count: 164

Registration Number: NCT04963231

Locations: 🇺🇸
Ten's Medical Center - Pediatric Endocrinology Clinic, Staten Island, New York, United States
🇺🇸
The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
🇺🇸
Endocrine Associates of Dallas and Plano, Dallas, Texas, United States

and more 33 locations

Open-Label Study of Setmelanotide in Hypothalamic Obesity

Phase 2

Completed

Conditions: Hypothalamic Obesity

Interventions: Drug: Setmelanotide

First Posted Date: 2021-01-26

Last Posted Date: 2025-02-07

Lead Sponsor: Rhythm Pharmaceuticals, Inc.

Target Recruit Count: 18

Registration Number: NCT04725240

Locations: 🇺🇸
Children's Minnesota, Saint Paul, Minnesota, United States
🇺🇸
Seattle Children's Research Institute, Seattle, Washington, United States
🇺🇸
Rady Children's Hospital, San Diego, California, United States

and more 2 locations

Drug Development Updates

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