Evidence map›Paper›PMID 35123544›Full record

Trial reportOrphanet journal of rare diseases2022

Quality of life outcomes in two phase 3 trials of setmelanotide in patients with obesity due to LEPR or POMC deficiency.

Peter Kühnen, Martin Wabitsch, Julia von Schnurbein, Costel Chirila, Usha G Mallya, Patrick Callahan, Ari Gnanasakthy, Christine Poitou, Philipp M Krabusch, Murray Stewart and 1 more

2 registry-linked trialsOpen access · goldAbstract readClinical Trial, Phase III
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Orphanet journal of rare diseases, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
3.1field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02896192 phase3completednot on this map

An Open-Label, 1-Year Trial, Including a Double-Blind Placebo-Controlled Withdrawal Period, of Setmelanotide (RM-493), a Melanocortin 4 Receptor (MC4R) Agonist, in Early Onset POMC Deficiency Obesity Due to Bi-Allelic Loss-of-Function POMC or PCSK1 Genetic Mutation

TypeinterventionalSponsorRhythm Pharmaceuticals, Inc.Ran2017 to 2020Enrolled15ConditionsPro-opiomelanocortin (POMC) Deficiency ObesityArmsSetmelanotide, Placebo
NCT03287960 phase3completednot on this map

An Open Label, 1-Year Trial, Including a Double-Blind Placebo-Controlled Withdrawal Period, of Setmelanotide (RM-493), a Melanocortin 4 Receptor (MC4R) Agonist, in Leptin Receptor (LEPR) Deficiency Obesity Due to Bi-Allelic Loss-of-Function LEPR Genetic Mutation

TypeinterventionalSponsorRhythm Pharmaceuticals, Inc.Ran2018 to 2020Enrolled15ConditionsLeptin Receptor Deficiency ObesityArmsSetmelanotide, Placebo
3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.

  1. Pooled it
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  4. Management of Childhood Obesity.International journal of molecular sciences · 2026
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  7. Weight Loss-Associated Remodeling of Adipose Tissue Immunometabolism.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 5 institutions in 3 countries.

Peter KühnenCharité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin und Humboldt-Universität zu Berlin, Institute for Experimental Pediatric Endocrinology, CVK, Augustenburger Platz 1, 13353, Berlin, Germany.
Martin WabitschDivision of Pediatric Endocrinology and Diabetes, Center for Rare Endocrine Diseases, Department of Pediatrics and Adolescent Medicine, University of Ulm, Eythstraße 24, 89075, Ulm, Germany.
Julia von SchnurbeinDivision of Pediatric Endocrinology and Diabetes, Center for Rare Endocrine Diseases, Department of Pediatrics and Adolescent Medicine, University of Ulm, Eythstraße 24, 89075, Ulm, Germany.
Costel ChirilaRTI Health Solutions, 3040 East Cornwallis Road, P.O. Box 12194, Research Triangle Park, NC, 27709-2194, USA.
Usha G MallyaRhythm Pharmaceuticals, Inc., 222 Berkeley Street, Suite 1200, Boston, MA, 02116, USA.
Patrick CallahanGenesis Research, 111 River Street, Suite 1120, Hoboken, NJ, 07030, USA.
Ari GnanasakthyRTI Health Solutions, 3040 East Cornwallis Road, P.O. Box 12194, Research Triangle Park, NC, 27709-2194, USA.
Christine PoitouNutrition Department, Assistance Publique Hôpitaux de Paris, Pitié-Salpêtrière Hospital, IE3M Building, Room 637, 6th floor, 91 boulevard de l'Hôpital, 75013, Paris, France.
Philipp M KrabuschCharité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin und Humboldt-Universität zu Berlin, Institute for Experimental Pediatric Endocrinology, CVK, Augustenburger Platz 1, 13353, Berlin, Germany.
Murray StewartRhythm Pharmaceuticals, Inc., 222 Berkeley Street, Suite 1200, Boston, MA, 02116, USA.
Karine ClémentNutrition Department, Assistance Publique Hôpitaux de Paris, Pitié-Salpêtrière Hospital, IE3M Building, Room 637, 6th floor, 91 boulevard de l'Hôpital, 75013, Paris, France. karine.clement@psl.aphp.fr.ORCID 0000-0002-2489-3355
Humboldt-Universität zu Berlin · DEInserm · FRJazz Pharmaceuticals (United States) · USRTI Health Solutions · USUniversität Ulm · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionIndividuals with proopiomelanocortin (POMC) or leptin receptor (LEPR) deficiency are young and experience severe obesity, hyperphagia, and comorbidities, which can impair quality of life (QOL).

methodsTwo pivotal Phase 3 trials explored the effect of setmelanotide on body weight and hunger in individuals with obesity due to POMC (NCT02896192) or LEPR (NCT03287960) deficiency. QOL and depression were investigated in parallel using the disease-specific, age-appropriate Impact of Weight on Quality of Life-Lite (IWQOL-Lite), Pediatric Quality of Life Inventory (PedsQL), and Patient Health Questionnaire-9 (PHQ-9).

resultsIn total, the POMC and LEPR trials enrolled 21 patients. Adults (≥ 18 years old; n = 7) had moderate-to-severe impairment in QOL at baseline, with mean (standard deviation [SD]) IWQOL-Lite total score 60.3 (13.2; maximum IWQOL-Lite total score = 100). The effect of setmelanotide on IWQOL-Lite total score was observed as soon as Week 5. Among those with scores at Week 52, 5 of 6 adults experienced a clinically meaningful improvement, with mean (SD) total scores increased from baseline by 24.2 (12.1) points. Children (6-12 years old; n = 2) and adolescents (13-17 years old; n = 4) had impaired QOL at baseline, with mean (SD) self-reported PedsQL total scores 53.3 (6.2) and 63.3 (29.1), respectively (maximum PedsQL total score = 100). Three of 5 patients experienced clinically meaningful improvement in PedsQL, with 2 children whose PedsQL total score increased by 28.3 and 3.3 points and 3 adolescents whose mean (SD) total score increased from baseline by 5.8 (18.3) points. Baseline mean (SD) PHQ-9 score (in those ≥ 12 years old) was 5.3 (3.8) and was generally maintained through Week 52.

conclusionsPatients with POMC or LEPR deficiency had impaired, and in some cases severely impaired, QOL before setmelanotide treatment. Setmelanotide improved QOL in patients as early as Week 5, with some patients no longer experiencing impaired QOL at Week 52. Improvements in QOL may be related to a reduction in hunger and body weight associated with setmelanotide. Because of the highly complex psychological consequences of rare genetic diseases of obesity, some patients may require a long period of treatment to improve QOL and benefit from interdisciplinary care.

Indexed as

Pro-OpiomelanocortinQuality of LifeAdolescentAdultalpha-MSHChildHumansObesityReceptors, LeptinSurveys and Questionnairesalpha-MSHPro-OpiomelanocortinReceptors, LeptinsetmelanotideDisease burdenHyperphagiaIWQOL-LiteMelanocortin receptorPedsQLPHQ-9Rare genetic diseases of obesity

Identifiers

PMID35123544
PMCPMC8817523
OpenAlexW4210264838

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.