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.
Highlights
Individuals with proopiomelanocortin (POMC) or leptin receptor (LEPR) deficiency are young and experience severe obesity, hyperphagia, and comorbidities, which can impair quality of life (QOL)
Study design Two pivotal Phase 3, single-arm, open-label trials with a double-blind placebo-controlled, withdrawal period investigated the effect of setmelanotide on body weight in individuals with obesity due to POMC or LEPR deficiency
Participant demographics A total of 21 patients were enrolled in the pivotal cohorts of the POMC and LEPR trials, with mean (SD) age and body mass index (BMI) of 21.2 (7.7) years and 44.5 (10.4) kg/m2, respectively; 16 patients were included in the designated use set (DUS) population
Summary
Individuals with proopiomelanocortin (POMC) or leptin receptor (LEPR) deficiency are young and experience severe obesity, hyperphagia, and comorbidities, which can impair quality of life (QOL). Kühnen et al Orphanet Journal of Rare Diseases (2022) 17:38 disease), the burden of social stigma, and impaired quality of life (QOL) [1,2,3,4,5,6] These burdens do not exist in isolation, but rather, impaired health status and social stigma can impact an individual’s QOL [1, 7]. Individuals with obesity are approximately twice as likely to have health concerns, chronic diseases, physical disability, or limitations to their daily life activities compared with nonobese individuals [7]. Individuals with severe obesity were 4 times as likely to have limitations to their daily life activities and were 30% more likely (odds ratio, 1.3) to have depression compared with nonobese individuals. Individuals with severe obesity were 4 times as likely to have limitations to their daily life activities and were 30% more likely (odds ratio, 1.3) to have depression compared with nonobese individuals. [7, 10]
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