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 Phase 1 Study to Evaluate the Pharmacokinetics of Setmelanotide in Subjects With Varying Degrees of Renal Impairment

Phase 1

Completed

Conditions: Renal Insufficiency

Interventions: Drug: Setmelanotide

First Posted Date: 2020-04-16

Last Posted Date: 2021-06-30

Lead Sponsor: Rhythm Pharmaceuticals, Inc.

Target Recruit Count: 32

Registration Number: NCT04348175

Locations: 🇺🇸
University of Miami, Miami, Florida, United States
🇺🇸
Alliance for Multispecialty Research, LLC, Knoxville, Tennessee, United States
🇺🇸
Orlando Clinical Research Center, Orlando, Florida, United States

and more 1 locations

Setmelanotide (RM-493), Melanocortin-4 Receptor (MC4R) Agonist, in Bardet-Biedl Syndrome (BBS) and Alström Syndrome (AS) Participants With Moderate to Severe Obesity

Phase 3

Completed

Conditions: Bardet Biedl Syndrome (BBS)
Alström Syndrome (AS)

Interventions: Drug: Setmelanotide
Drug: Placebo

First Posted Date: 2018-11-19

Last Posted Date: 2023-12-01

Lead Sponsor: Rhythm Pharmaceuticals, Inc.

Target Recruit Count: 52

Registration Number: NCT03746522

Locations: 🇺🇸
Wr-McCr, Llc, San Diego, California, United States
🇺🇸
Columbia University Center, New York, New York, United States
🇺🇸
M3 Wake Research, Raleigh, North Carolina, United States

and more 9 locations

Long Term Extension Trial of Setmelanotide

Phase 2

Completed

Conditions: Obesity Associated With Defects in Leptin-melanocortin Pathway

Interventions: Drug: Setmelanotide

First Posted Date: 2018-08-29

Last Posted Date: 2025-04-08

Lead Sponsor: Rhythm Pharmaceuticals, Inc.

Target Recruit Count: 205

Registration Number: NCT03651765

Locations: 🇺🇸
Obesity Institute, Geisinger Clinic, Danville, Pennsylvania, United States
🇺🇸
Wake Research, Raleigh, North Carolina, United States
🇺🇸
Wake Research TN, Chattanooga, Tennessee, United States

and more 24 locations

Setmelanotide for the Treatment of Leptin Receptor (LEPR) Deficiency Obesity

Phase 3

Completed

Conditions: Leptin Receptor Deficiency Obesity

Interventions: Drug: Setmelanotide
Drug: Placebo

First Posted Date: 2017-09-19

Last Posted Date: 2023-05-23

Lead Sponsor: Rhythm Pharmaceuticals, Inc.

Target Recruit Count: 15

Registration Number: NCT03287960

Locations: 🇳🇱
Erasmus Medical Center, Rotterdam, Netherlands
🇩🇪
University of Ulm, Ulm, Germany
🇨🇦
Markham Stouffville Hospital, Markham, Ontario, Canada

and more 3 locations

Setmelanotide in a Single Patient With Partial Lipodystrophy

Phase 2

Completed

Conditions: Hypertriglyceridemia
Obesity

Interventions: Drug: Setmelanotide

First Posted Date: 2017-08-25

Last Posted Date: 2022-01-04

Lead Sponsor: Rhythm Pharmaceuticals, Inc.

Target Recruit Count: 1

Registration Number: NCT03262610

Locations: 🇺🇸
University of Michigan, Ann Arbor, Michigan, United States

Setmelanotide Phase 2 Treatment Trial in Participants With Rare Genetic Disorders of Obesity

Phase 2

Completed

Conditions: Genetic Obesity
Obesity
Obesity Due to Melanocortin 4 Receptor Deficiency

Interventions: Drug: Setmelanotide

First Posted Date: 2017-01-06

Last Posted Date: 2023-08-18

Lead Sponsor: Rhythm Pharmaceuticals, Inc.

Target Recruit Count: 213

Registration Number: NCT03013543

Locations: 🇺🇸
AXIS South Florida Clinical Trials, Hialeah, Florida, United States
🇺🇸
Synexus Clinical Research US, Inc. - Akron, Akron, Ohio, United States
🇺🇸
Baylor College of Medicine, Houston, Texas, United States

and more 54 locations

Setmelanotide for the Treatment of Early-Onset Pro-Opiomelanocortin (POMC) Deficiency Obesity

Phase 3

Completed

Conditions: Pro-opiomelanocortin (POMC) Deficiency Obesity

Interventions: Drug: Setmelanotide
Drug: Placebo

First Posted Date: 2016-09-12

Last Posted Date: 2023-09-21

Lead Sponsor: Rhythm Pharmaceuticals, Inc.

Target Recruit Count: 15

Registration Number: NCT02896192

Locations: 🇩🇪
Charité Campus Virchow-Klinikum / Institute for Experimental Pediatric Endocrinology, Berlin, Germany
🇬🇧
University of Cambridge Metabolic Research Laboratories, Cambridge, United Kingdom
🇺🇸
Honor Health Research Institute, Scottsdale, Arizona, United States

and more 4 locations

RM-493 Treatment Trial in Proopiomelanocortin (POMC) Deficient Patients

Phase 2

Conditions: Homozygous or Compound Heterozygous POMC, LEPR or PCSK1 Gene Mutation

Interventions: Drug: RM-493

First Posted Date: 2015-07-24

Last Posted Date: 2016-02-22

Lead Sponsor: Charite University, Berlin, Germany

Target Recruit Count: 10

Registration Number: NCT02507492

Locations: 🇩🇪
Charité - Universitätsmedizin Berlin, Berlin, Germany

Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of RM-493 Administered to Healthy, Obese, Non-diabetic Volunteers

Phase 1

Completed

Conditions: Obese
Overweight

Interventions: Drug: Placebo
Drug: RM-493

First Posted Date: 2015-05-01

Last Posted Date: 2015-05-01

Lead Sponsor: Rhythm Pharmaceuticals, Inc.

Target Recruit Count: 57

Registration Number: NCT02431442

Phase 2 Trial to Evaluate Safety and Efficacy of Setmelanotide (RM-493) in Obese Participants With Prader-Willi Syndrome

Phase 2

Completed

Conditions: Prader-Willi Syndrome

Interventions: Drug: Setmelanotide
Drug: Placebo

First Posted Date: 2014-12-08

Last Posted Date: 2023-07-27

Lead Sponsor: Rhythm Pharmaceuticals, Inc.

Target Recruit Count: 40

Registration Number: NCT02311673

Locations: 🇺🇸
Kansas University Medical Center, Kansas City, Kansas, United States
🇺🇸
Winthrop University Hospital, Mineola, New York, United States
🇺🇸
University of California Irvine, Irvine, California, United States

and more 2 locations

Drug Development Updates

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