Natural History of Obesity Due to POMC, PCSK1, and LEPR Deficiency and the Impact of Setmelanotide.

ABSTRACT:

Context

Rare homozygous or biallelic variants in POMC, PCSK1, and LEPR can disrupt signaling through the melanocortin-4 receptor (MC4R) pathway, resulting in hyperphagia and severe early-onset obesity. In pivotal Phase 3 clinical trials, treatment with the MC4R agonist setmelanotide reduced hunger and weight in patients with obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency.

Objective

To characterize the historical weight trajectory in these patients.

Methods

This analysis included data from 2 pivotal single-arm, open-label, Phase 3 trials (NCT02896192, NCT03287960). These were multicenter trials. Patients had obesity due to POMC/PCSK1 or LEPR deficiency. During t

SUBMITTER: Wabitsch M 

PROVIDER: S-EPMC9070354 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature