ESPE2021 Free Communications Fat, Metabolism and Obesity (6 abstracts)
Phase 3 Trial of Setmelanotide in Participants With Bardet-Biedl Syndrome: Placebo-Controlled Results
Jesús Argente 1,2 , Karine Clément 3,4 , Hélène Dollfus 5 , Joan Han 6 , Andrea Haqq 7 , Gabriel Martos-Moreno 1 , Robert Mittleman 8 , Murray Stewart 8 , Matt Webster 8 , Jack Yanovski 9 , Guojun Yuan 8 & Robert Haws 10
1Department of Pediatrics and Pediatric Endocrinology, Universidad Autónoma de Madrid, University Hospital Niño Jesús, CIBER “Fisiopatología de la Obesidad y Nutrición” (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.;2IMDEA Institute, Madrid, Spain.;3Assistance Publique Hôpitaux de Paris, Nutrition Department, Pitié-Salpêtrière Hospital, Human Nutrition Research Center,, Paris, France.;4Sorbonne Université, INSERM, NutriOmics Research Unit, Paris, France.;5Hôpitaux Universitaires de Strasbourg, CARGO and Department of Medical Genetics, Strasbourg, France.;6Division of Pediatric Endocrinology, Department of Pediatrics, Mount Sinai Hospital, Icahn School of Medicine at Mount Sinai, New York, USA.;7Division of Pediatric Endocrinology, University of Alberta, Edmonton, Canada.;8Rhythm Pharmaceuticals, Inc., Boston, USA.;9Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, USA.;10Marshfield Clinic Research Institute, Marshfield, USA
Background: In a Phase 3 trial in participants with obesity due to Bardet-Biedl syndrome (BBS) and Alström syndrome, setmelanotide was associated with significant reduction from baseline in body weight and hunger at Week 52 (primary endpoint), with outcomes driven by responses in individuals with BBS.
Methods: In the same trial (NCT03746522), individuals with BBS or Alström syndrome were randomized and received setmelanotide or placebo for 14 weeks. Obesity was defined as weight >97th percentile in those aged 6–15 years and body mass index ≥30 kg/m2 in those aged ≥16 years. Body weight, hunger, and adverse events (AEs) were assessed. Because all primary endpoint responders were participants with BBS, preliminary data are reported for those participants.
Results: 32 participants with BBS were enrolled, 29 with age ≥12 years. Relative to placebo (negligible weight loss of −0.2 kg), there were significant reductions in body weight (Table 1) and hunger (Table 2) with setmelanotide. There was 1 serious treatment-related AE of anaphylactic reaction that occurred in a participant during placebo treatment. In all participants, including those with Alström syndrome, the most common AE was injection site erythema (setmelanotide, 42.1%; placebo, 36.8%). AEs were generally similar between treatment groups; however, 11 participants (57.9%) receiving setmelanotide experienced skin hyperpigmentation compared with 0 participants receiving placebo.
| Treatment group | |||
| Setmelanotide, mean (SD) (n = 14) | Placebo, mean (SD) (n = 15) | Mean difference (95% CI) | |
| Change, kg | −4.0 (5.3) | −0.2 (2.9) | −3.8 (−7.0, −0.6) P = 0.0113 |
| Percent change | −3.2% (4.5) | −0.2% (2.4) | −3.0% (−5.6, −0.3) P = 0.0164 |
| BBS, Bardet-Biedl syndrome; CI, confidence interval; SD, standard deviation. | |||
| Treatment group | |||
| Setmelanotide, mean (SD) (n = 5) | Placebo, mean (SD)(n = 9) | Mean difference (95% CI) | |
| Change | −2.4 (1.2) | −1.0 (1.2) | −1.4 (−2.8, 0.1) P = 0.0311 |
| Percent change | −34.8% (18.5) | −14.5% (15.8) | −20.4% (−40.7, 0) P = 0.0249 |
| BBS, Bardet-Biedl syndrome; CI, confidence interval; SD, standard deviation.aAged ≥12 years and without cognitive impairment.bWeekly average of hunger scores. | |||
Conclusions: Participants with BBS who received setmelanotide experienced significantly greater weight loss and hunger reduction versus those who received placebo. Of note, participants with BBS who received placebo had negligible weight loss. Setmelanotide may be a promising treatment for obesity in individuals with BBS.
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