Timing of Onset of Adverse Events With Setmelanotide, an MC4R Agonist, in Patients With Severe Obesity Due to LEPR or POMC Deficiency

Clément K, van den Akker E, Gordon G, Yuan G, Kühnen P

Journal of the Endocrine Society3 May 2021

PMCIDPMC8265764PepBankPUB-95645849

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Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: CC BY-NC-ND. Results still quote short attributed sentences.

Results from this study16

16 results from studies that gave the peptide. 16 results from people.

01HumanNon-randomized trialSafety outcome
All patients with POMC/PCSK1 or LEPR deficiency experienced at least one treatment-emergent adverse event during setmelanotide treatment.
In plain wordsAll patients with these genetic deficiencies experienced at least one adverse event during setmelanotide treatment.
Peptide
Setmelanotide
Outcome
Not applicableAny treatment-emergent adverse event
Study
n = 35
Outcome group
Adverse events · Whole body
Studied dose
0.25 to 3.0 mg dailyAs given in this study (human).
Source sentences
Summary
All patients experienced ≥1 TEAE, the most common being skin hyperpigmentation (85.7%), injection site erythema (68.6%), nausea (57.1%), and headache (51.4%).
2 context sentences(design, population, supporting numbers)
Summary · context
The timing of AE onset with setmelanotide was evaluated in a pooled set of patients with POMC/PCSK1 or LEPR deficiency who received setmelanotide in Phase 2 (RM-493-011 [NCT02507492]) or Phase 3 (RM-493-012 [NCT02896192] and RM-493-015 [NCT03287960]) clinical trials.
Summary · context
Daily setmelanotide dose ranged from 0.25 to 3.0 mg.
Report a problemFND-9564584901
02HumanNon-randomized trialSafety outcome
During setmelanotide treatment, skin hyperpigmentation occurred in 85.7% of patients with POMC/PCSK1 or LEPR deficiency.
In plain wordsDuring setmelanotide treatment, skin darkening occurred in 85.7% of patients with these genetic deficiencies.
Peptide
Setmelanotide
Outcome
Not applicableSkin hyperpigmentation
Study
n = 35
Outcome group
Adverse events · Skin and wound
Studied dose
0.25 to 3.0 mg dailyAs given in this study (human).
Measurements
Patients with skin hyperpigmentation
85.7%
Pooled phase 2 and 3 trials, 35 patients, daily dose 0.25 to 3.0 mg
Source sentences
Summary
All patients experienced ≥1 TEAE, the most common being skin hyperpigmentation (85.7%), injection site erythema (68.6%), nausea (57.1%), and headache (51.4%).
2 context sentences(design, population, supporting numbers)
Summary · context
The timing of AE onset with setmelanotide was evaluated in a pooled set of patients with POMC/PCSK1 or LEPR deficiency who received setmelanotide in Phase 2 (RM-493-011 [NCT02507492]) or Phase 3 (RM-493-012 [NCT02896192] and RM-493-015 [NCT03287960]) clinical trials.
Summary · context
Daily setmelanotide dose ranged from 0.25 to 3.0 mg.
Report a problemFND-9564584902
03HumanNon-randomized trialSafety outcome
During setmelanotide treatment, injection site erythema occurred in 68.6% of patients with POMC/PCSK1 or LEPR deficiency.
In plain wordsDuring setmelanotide treatment, injection site redness occurred in 68.6% of patients with these genetic deficiencies.
Peptide
Setmelanotide
Outcome
Not applicableInjection site erythema
Study
n = 35
Outcome group
Adverse events · Skin and wound
Studied dose
0.25 to 3.0 mg dailyAs given in this study (human).
Measurements
Patients with injection site erythema
68.6%
Pooled phase 2 and 3 trials, 35 patients, daily dose 0.25 to 3.0 mg
Source sentences
Summary
All patients experienced ≥1 TEAE, the most common being skin hyperpigmentation (85.7%), injection site erythema (68.6%), nausea (57.1%), and headache (51.4%).
2 context sentences(design, population, supporting numbers)
Summary · context
The timing of AE onset with setmelanotide was evaluated in a pooled set of patients with POMC/PCSK1 or LEPR deficiency who received setmelanotide in Phase 2 (RM-493-011 [NCT02507492]) or Phase 3 (RM-493-012 [NCT02896192] and RM-493-015 [NCT03287960]) clinical trials.
Summary · context
Daily setmelanotide dose ranged from 0.25 to 3.0 mg.
Report a problemFND-9564584903
04HumanNon-randomized trialSafety outcome
During setmelanotide treatment, nausea occurred in 57.1% of patients with POMC/PCSK1 or LEPR deficiency (20/35).
In plain wordsDuring setmelanotide treatment, nausea occurred in 57.1% of patients with these genetic deficiencies.
Peptide
Setmelanotide
Outcome
Not applicableNausea
Study
n = 35
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
0.25 to 3.0 mg dailyAs given in this study (human).
Measurements
Patients with nausea
57.1%
Pooled phase 2 and 3 trials, 35 patients, daily dose 0.25 to 3.0 mg
Patients with nausea
20 patients
Pooled phase 2 and 3 trials, 35 patients, daily dose 0.25 to 3.0 mg
Source sentences
Summary
For AEs of special interest, hyperpigmentation disorders occurred in 85.7% of patients (30/35), disturbances in sexual arousal in 17.1% (6/35), nausea in 57.1% (20/35), vomiting in 28.6% (10/35), and ISRs in 88.6% (31/35).
2 context sentences(design, population, supporting numbers)
Summary · context
The timing of AE onset with setmelanotide was evaluated in a pooled set of patients with POMC/PCSK1 or LEPR deficiency who received setmelanotide in Phase 2 (RM-493-011 [NCT02507492]) or Phase 3 (RM-493-012 [NCT02896192] and RM-493-015 [NCT03287960]) clinical trials.
Summary · context
Daily setmelanotide dose ranged from 0.25 to 3.0 mg.
Report a problemFND-9564584904
05HumanNon-randomized trialSafety outcome
During setmelanotide treatment, headache occurred in 51.4% of patients with POMC/PCSK1 or LEPR deficiency.
In plain wordsDuring setmelanotide treatment, headache occurred in 51.4% of patients with these genetic deficiencies.
Peptide
Setmelanotide
Outcome
Not applicableHeadache
Study
n = 35
Outcome group
Adverse events · Nervous system and cognition
Studied dose
0.25 to 3.0 mg dailyAs given in this study (human).
Measurements
Patients with headache
51.4%
Pooled phase 2 and 3 trials, 35 patients, daily dose 0.25 to 3.0 mg
Source sentences
Summary
All patients experienced ≥1 TEAE, the most common being skin hyperpigmentation (85.7%), injection site erythema (68.6%), nausea (57.1%), and headache (51.4%).
2 context sentences(design, population, supporting numbers)
Summary · context
The timing of AE onset with setmelanotide was evaluated in a pooled set of patients with POMC/PCSK1 or LEPR deficiency who received setmelanotide in Phase 2 (RM-493-011 [NCT02507492]) or Phase 3 (RM-493-012 [NCT02896192] and RM-493-015 [NCT03287960]) clinical trials.
Summary · context
Daily setmelanotide dose ranged from 0.25 to 3.0 mg.
Report a problemFND-9564584905
06HumanNon-randomized trialSafety outcome
During setmelanotide treatment, hyperpigmentation disorders occurred in 85.7% of patients with POMC/PCSK1 or LEPR deficiency (30/35).
In plain wordsDuring setmelanotide treatment, pigmentation disorders occurred in 85.7% of patients with these genetic deficiencies.
Peptide
Setmelanotide
Outcome
Not applicableHyperpigmentation disorders
Study
n = 35
Outcome group
Adverse events · Skin and wound
Studied dose
0.25 to 3.0 mg dailyAs given in this study (human).
Measurements
Patients with hyperpigmentation disorders
85.7%
Pooled phase 2 and 3 trials, 35 patients, daily dose 0.25 to 3.0 mg
Patients with hyperpigmentation disorders
30 patients
Pooled phase 2 and 3 trials, 35 patients, daily dose 0.25 to 3.0 mg
Source sentences
Summary
For AEs of special interest, hyperpigmentation disorders occurred in 85.7% of patients (30/35), disturbances in sexual arousal in 17.1% (6/35), nausea in 57.1% (20/35), vomiting in 28.6% (10/35), and ISRs in 88.6% (31/35).
2 context sentences(design, population, supporting numbers)
Summary · context
The timing of AE onset with setmelanotide was evaluated in a pooled set of patients with POMC/PCSK1 or LEPR deficiency who received setmelanotide in Phase 2 (RM-493-011 [NCT02507492]) or Phase 3 (RM-493-012 [NCT02896192] and RM-493-015 [NCT03287960]) clinical trials.
Summary · context
Daily setmelanotide dose ranged from 0.25 to 3.0 mg.
Report a problemFND-9564584906
07HumanNon-randomized trialSafety outcome
During setmelanotide treatment, disturbances in sexual arousal occurred in 17.1% of patients with POMC/PCSK1 or LEPR deficiency (6/35).
In plain wordsDuring setmelanotide treatment, sexual arousal disturbances occurred in 17.1% of patients with these genetic deficiencies.
Peptide
Setmelanotide
Outcome
Not applicableDisturbances in sexual arousal
Study
n = 35
Outcome group
Adverse events · Reproductive and sexual health
Studied dose
0.25 to 3.0 mg dailyAs given in this study (human).
Measurements
Patients with disturbances in sexual arousal
17.1%
Pooled POMC/PCSK1 and LEPR deficiency patients (n=35)
Patients with disturbances in sexual arousal
6 patients
Pooled POMC/PCSK1 and LEPR deficiency patients (n=35)
Source sentences
Summary
For AEs of special interest, hyperpigmentation disorders occurred in 85.7% of patients (30/35), disturbances in sexual arousal in 17.1% (6/35), nausea in 57.1% (20/35), vomiting in 28.6% (10/35), and ISRs in 88.6% (31/35).
2 context sentences(design, population, supporting numbers)
Summary · context
The timing of AE onset with setmelanotide was evaluated in a pooled set of patients with POMC/PCSK1 or LEPR deficiency who received setmelanotide in Phase 2 (RM-493-011 [NCT02507492]) or Phase 3 (RM-493-012 [NCT02896192] and RM-493-015 [NCT03287960]) clinical trials.
Summary · context
Daily setmelanotide dose ranged from 0.25 to 3.0 mg.
Report a problemFND-9564584907
08HumanNon-randomized trialSafety outcome
During setmelanotide treatment, vomiting occurred in 28.6% of patients with POMC/PCSK1 or LEPR deficiency (10/35).
In plain wordsDuring setmelanotide treatment, vomiting occurred in 28.6% of patients with these genetic deficiencies.
Peptide
Setmelanotide
Outcome
Not applicableVomiting
Study
n = 35
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
0.25 to 3.0 mg dailyAs given in this study (human).
Measurements
Patients with vomiting
28.6%
Pooled POMC/PCSK1 and LEPR deficiency patients (n=35)
Patients with vomiting
10 patients
Pooled POMC/PCSK1 and LEPR deficiency patients (n=35)
Source sentences
Summary
For AEs of special interest, hyperpigmentation disorders occurred in 85.7% of patients (30/35), disturbances in sexual arousal in 17.1% (6/35), nausea in 57.1% (20/35), vomiting in 28.6% (10/35), and ISRs in 88.6% (31/35).
2 context sentences(design, population, supporting numbers)
Summary · context
The timing of AE onset with setmelanotide was evaluated in a pooled set of patients with POMC/PCSK1 or LEPR deficiency who received setmelanotide in Phase 2 (RM-493-011 [NCT02507492]) or Phase 3 (RM-493-012 [NCT02896192] and RM-493-015 [NCT03287960]) clinical trials.
Summary · context
Daily setmelanotide dose ranged from 0.25 to 3.0 mg.
Report a problemFND-9564584908
09HumanNon-randomized trialSafety outcome
During setmelanotide treatment, injection site reactions occurred in 88.6% of patients with POMC/PCSK1 or LEPR deficiency (31/35).
In plain wordsDuring setmelanotide treatment, injection site reactions occurred in 88.6% of patients with these genetic deficiencies.
Peptide
Setmelanotide
Outcome
Not applicableInjection site reactions
Study
n = 35
Outcome group
Adverse events · Skin and wound
Studied dose
0.25 to 3.0 mg dailyAs given in this study (human).
Measurements
Patients with injection site reactions
88.6%
Pooled POMC/PCSK1 and LEPR deficiency patients (n=35)
Patients with injection site reactions
31 patients
Pooled POMC/PCSK1 and LEPR deficiency patients (n=35)
Source sentences
Summary
For AEs of special interest, hyperpigmentation disorders occurred in 85.7% of patients (30/35), disturbances in sexual arousal in 17.1% (6/35), nausea in 57.1% (20/35), vomiting in 28.6% (10/35), and ISRs in 88.6% (31/35).
2 context sentences(design, population, supporting numbers)
Summary · context
The timing of AE onset with setmelanotide was evaluated in a pooled set of patients with POMC/PCSK1 or LEPR deficiency who received setmelanotide in Phase 2 (RM-493-011 [NCT02507492]) or Phase 3 (RM-493-012 [NCT02896192] and RM-493-015 [NCT03287960]) clinical trials.
Summary · context
Daily setmelanotide dose ranged from 0.25 to 3.0 mg.
Report a problemFND-9564584909
10HumanNon-randomized trialSafety outcome
Eighteen serious adverse events occurred in setmelanotide-treated patients with POMC/PCSK1 or LEPR deficiency, none interpreted as drug-related.
In plain wordsEighteen serious adverse events occurred during setmelanotide treatment in these patients, none interpreted as drug-related.
Peptide
Setmelanotide
Outcome
Not applicableSerious adverse events
Study
n = 35
Outcome group
Adverse events · Whole body
Studied dose
0.25 to 3.0 mg dailyAs given in this study (human).
Measurements
Serious adverse events
18 events
Pooled POMC/PCSK1 and LEPR deficiency patients (n=35)
Source sentences
Summary
Eighteen serious AEs occurred, none were interpreted as related to the study drug.
2 context sentences(design, population, supporting numbers)
Summary · context
The timing of AE onset with setmelanotide was evaluated in a pooled set of patients with POMC/PCSK1 or LEPR deficiency who received setmelanotide in Phase 2 (RM-493-011 [NCT02507492]) or Phase 3 (RM-493-012 [NCT02896192] and RM-493-015 [NCT03287960]) clinical trials.
Summary · context
Daily setmelanotide dose ranged from 0.25 to 3.0 mg.
Report a problemFND-9564584915
11HumanNon-randomized trialSafety outcome
In patients with POMC/PCSK1 or LEPR deficiency receiving setmelanotide, all adverse events of special interest except hyperpigmentation occurred intermittently.
In plain wordsIn patients with these genetic deficiencies receiving setmelanotide, all tracked adverse events of special interest except skin darkening occurred intermittently.
Peptide
Setmelanotide
Outcome
Not applicableIntermittent adverse events
Study
n = 35
Outcome group
Adverse events · Whole body
Studied dose
0.25 to 3.0 mg dailyAs given in this study (human).
Source sentences
Summary
Apart from hyperpigmentation, all AEs occurred intermittently.
2 context sentences(design, population, supporting numbers)
Summary · context
The timing of AE onset with setmelanotide was evaluated in a pooled set of patients with POMC/PCSK1 or LEPR deficiency who received setmelanotide in Phase 2 (RM-493-011 [NCT02507492]) or Phase 3 (RM-493-012 [NCT02896192] and RM-493-015 [NCT03287960]) clinical trials.
Summary · context
Daily setmelanotide dose ranged from 0.25 to 3.0 mg.
Report a problemFND-9564584916
12HumanNon-randomized trialSafety outcome
In setmelanotide-treated patients, 34/53 hyperpigmentation disorder events (64.2%) began during Month 1.
In plain wordsIn patients receiving setmelanotide, 64.2% of pigmentation disorder events began during Month 1.
Peptide
Setmelanotide
Outcome
Not applicableHyperpigmentation onset in Month 1
Study
n: not reported in source
Outcome group
Adverse events · Skin and wound
Studied dose
0.25 to 3.0 mg dailyAs given in this study (human).
Measurements
Hyperpigmentation disorder events with onset in Month 1
34 events
of 53 events
Hyperpigmentation disorder events with onset in Month 1
64.2%
34/53 events
Source sentences
Summary
The onset of most hyperpigmentation disorder (34/53 events; 64.2%) and disturbances in sexual arousal (6/11 events; 54.6%) AEs were during Month 1 after starting setmelanotide.
2 context sentences(design, population, supporting numbers)
Summary · context
The timing of AE onset with setmelanotide was evaluated in a pooled set of patients with POMC/PCSK1 or LEPR deficiency who received setmelanotide in Phase 2 (RM-493-011 [NCT02507492]) or Phase 3 (RM-493-012 [NCT02896192] and RM-493-015 [NCT03287960]) clinical trials.
Summary · context
Daily setmelanotide dose ranged from 0.25 to 3.0 mg.
Report a problemFND-9564584910
13HumanNon-randomized trialSafety outcome
In setmelanotide-treated patients, 6/11 sexual arousal disturbance events (54.6%) began during Month 1.
In plain wordsIn patients receiving setmelanotide, 54.6% of sexual arousal disturbance events began during Month 1.
Peptide
Setmelanotide
Outcome
Not applicableSexual arousal disturbance onset in Month 1
Study
n: not reported in source
Outcome group
Adverse events · Reproductive and sexual health
Studied dose
0.25 to 3.0 mg dailyAs given in this study (human).
Measurements
Sexual arousal disturbance events with onset in Month 1
6 events
of 11 events
Sexual arousal disturbance events with onset in Month 1
54.6%
6/11 events
Source sentences
Summary
The onset of most hyperpigmentation disorder (34/53 events; 64.2%) and disturbances in sexual arousal (6/11 events; 54.6%) AEs were during Month 1 after starting setmelanotide.
2 context sentences(design, population, supporting numbers)
Summary · context
The timing of AE onset with setmelanotide was evaluated in a pooled set of patients with POMC/PCSK1 or LEPR deficiency who received setmelanotide in Phase 2 (RM-493-011 [NCT02507492]) or Phase 3 (RM-493-012 [NCT02896192] and RM-493-015 [NCT03287960]) clinical trials.
Summary · context
Daily setmelanotide dose ranged from 0.25 to 3.0 mg.
Report a problemFND-9564584911
14HumanNon-randomized trialSafety outcome
In setmelanotide-treated patients, nausea onset was most frequent during Month 1, accounting for 12/34 events (35.3%).
In plain wordsIn patients receiving setmelanotide, nausea onset was most frequent during Month 1, with 35.3% of events.
Peptide
Setmelanotide
Outcome
Not applicableNausea onset in Month 1
Study
n: not reported in source
Outcome group
Adverse events · Gastrointestinal
Studied dose
0.25 to 3.0 mg dailyAs given in this study (human).
Measurements
Nausea events with onset in Month 1
12 events
of 34 events
Nausea events with onset in Month 1
35.3%
12/34 events
Source sentences
Summary
Onset of nausea and vomiting were most frequent during Month 1 of treatment (nausea: 12/34 events [35.3%]; vomiting: 6/19 events [31.6%]).
2 context sentences(design, population, supporting numbers)
Summary · context
The timing of AE onset with setmelanotide was evaluated in a pooled set of patients with POMC/PCSK1 or LEPR deficiency who received setmelanotide in Phase 2 (RM-493-011 [NCT02507492]) or Phase 3 (RM-493-012 [NCT02896192] and RM-493-015 [NCT03287960]) clinical trials.
Summary · context
Daily setmelanotide dose ranged from 0.25 to 3.0 mg.
Report a problemFND-9564584912
15HumanNon-randomized trialSafety outcome
In setmelanotide-treated patients, vomiting onset was most frequent during Month 1, accounting for 6/19 events (31.6%).
In plain wordsIn patients receiving setmelanotide, vomiting onset was most frequent during Month 1, with 31.6% of events.
Peptide
Setmelanotide
Outcome
Not applicableVomiting onset in Month 1
Study
n: not reported in source
Outcome group
Adverse events · Gastrointestinal
Studied dose
0.25 to 3.0 mg dailyAs given in this study (human).
Measurements
Vomiting events with onset in Month 1
6 events
of 19 events
Vomiting events with onset in Month 1
31.6%
6/19 events
Source sentences
Summary
Onset of nausea and vomiting were most frequent during Month 1 of treatment (nausea: 12/34 events [35.3%]; vomiting: 6/19 events [31.6%]).
2 context sentences(design, population, supporting numbers)
Summary · context
The timing of AE onset with setmelanotide was evaluated in a pooled set of patients with POMC/PCSK1 or LEPR deficiency who received setmelanotide in Phase 2 (RM-493-011 [NCT02507492]) or Phase 3 (RM-493-012 [NCT02896192] and RM-493-015 [NCT03287960]) clinical trials.
Summary · context
Daily setmelanotide dose ranged from 0.25 to 3.0 mg.
Report a problemFND-9564584913
16HumanNon-randomized trialSafety outcome
In setmelanotide-treated patients, injection site reactions occurred throughout treatment, with 91/219 events (41.6%) beginning within Month 1.
In plain wordsIn patients receiving setmelanotide, injection site reactions occurred throughout treatment, with 41.6% beginning within Month 1.
Peptide
Setmelanotide
Outcome
Not applicableInjection site reaction onset
Study
n: not reported in source
Outcome group
Adverse events · Skin and wound
Studied dose
0.25 to 3.0 mg dailyAs given in this study (human).
Measurements
Injection site reaction events with onset in Month 1
91 events
of 219 events
Injection site reaction events with onset in Month 1
41.6%
91/219 events
Source sentences
Summary
ISRs occurred throughout the trial, with 41.6% (91/219 events) having an onset within Month 1 of treatment.
2 context sentences(design, population, supporting numbers)
Summary · context
The timing of AE onset with setmelanotide was evaluated in a pooled set of patients with POMC/PCSK1 or LEPR deficiency who received setmelanotide in Phase 2 (RM-493-011 [NCT02507492]) or Phase 3 (RM-493-012 [NCT02896192] and RM-493-015 [NCT03287960]) clinical trials.
Summary · context
Daily setmelanotide dose ranged from 0.25 to 3.0 mg.
Report a problemFND-9564584914

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Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
28 Oct 2026, 02:03 UTC
Study results updated
Version 1
27 Oct 2026, 16:36 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

Publication types

Abstract

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