Imcivree (setmelanotide) / Rhythm Pharma - LARVOL DELTA

Rhythm Pharmaceuticals Announces Health Canada Approval of IMCIVREE (setmelanotide) for Weight Management in Adult and Pediatric Patients 4 years of Age and Older with Acquired Hypothalamic Obesity (Yahoo Finance) - "IMCIVREE, a melanocortin-4 receptor (MC4R) agonist, is the first targeted therapy approved in Canada to treat acquired HO. The Health Canada approval is based on the positive pivotal Phase 3 TRANSCEND trial of setmelanotide in 142 patients with acquired HO. The global study met its primary endpoint, demonstrating a statistically significant 18.8% placebo-adjusted reduction in body mass index (BMI)....Following this approval, Rhythm will continue with supporting access to IMCIVREE for patients with acquired HO across Canada."

Canada approval • Hypothalamic Injury-associated Obesity

Setmelanotide-induced hyperpigmentation and nevus changes in two adult siblings with Bardet-Biedl syndrome (EADV 2026) - No abstract available

Clinical • Bardet–Biedl Syndrome • Inherited Retinal Dystrophy • Ophthalmology

Recent Advances in Glucagon-Like Peptide-1 Receptor and Melanocortin-4 Receptor Agonists for the Treatment of Obesity and Type 2 Diabetes. (PubMed, Horm Metab Res) - "Glucagon-like peptide-1 receptor agonists, such as semaglutide and liraglutide, promote insulin secretion, suppress appetite, and result in effective weight loss and glycemic control...Melanocortin-4 receptor agonists act via the central nervous system to reduce appetite and increase energy expenditure, with setmelanotide showing efficacy in genetic obesity...Glucagon-like peptide-1 receptor and melanocortin-4 receptor agonists, particularly when used as dual or triple agents, represent promising therapeutic innovations for obesity and type 2 diabetes. The development of oral formulations further enhances treatment convenience and adherence, paving the way for improved clinical outcomes."

Journal • Cardiovascular • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Setmelanotide Response Variability in Two Genetically Confirmed Pediatric Kidney Transplant Recipients with Bardet-Biedl Syndrome. (PubMed, Int J Mol Sci) - "In these two patients, setmelanotide was not associated with graft deterioration or altered cyclosporine trough concentrations, although two cases cannot establish safety. The divergent trajectories highlight interindividual variability; the role of PCSK1 N221D remains uncertain, and these observations are hypothesis-generating."

Journal • Bardet–Biedl Syndrome • Genetic Disorders • Inherited Retinal Dystrophy • Nephrology • Obesity • Ophthalmology • Pediatrics • Transplantation • PCSK1

Sequential liraglutide and setmelanotide therapy in Bardet-Biedl Syndrome: metabolic and renal outcomes in a real-world case report and literature review. (PubMed, Nephron) - "Setmelanotide promoted clinically meaningful weight loss and improved liver, kidney, and metabolic parameters in an adult patient carrying BBS10-likely pathogenic variants. Together with emerging evidence for interventional studies, these findings suggest that MC4R agonism may confer organ-level and cardiometabolic benefits beyond weight reduction."

Journal • Real-world evidence • Bardet–Biedl Syndrome • Dyslipidemia • Genetic Disorders • Hepatology • Hypertriglyceridemia • Inherited Retinal Dystrophy • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Nephrology • Obesity • Ophthalmology • Renal Disease • MC4R

Two-Year Phase 3 Trial Results of Setmelanotide in Patients with Acquired Hypothalamic Obesity (OBESITY WEEK 2026) - No abstract available

Clinical • P3 data • Genetic Disorders • Hypothalamic Injury-associated Obesity • Obesity

In addition, the following oral and poster presentations will be presented at ESPE (Rhythm Press Release) - "Weight outcomes at 5–6 years of setmelanotide in paediatric patients with POMC or LEPR deficiency or Bardet–Biedl syndrome and obesity; Post hoc analysis to determine the impact of setmelanotide on metabolic syndrome severity and risk score in patients with acquired hypothalamic obesity from the Phase 3 TRANSCEND trial; The association of clinical features of Bardet–Biedl syndrome in a large population of patients with obesity and a positive genetic test for biallelic BBS variants; and Clinical features associated with pathogenic or likely pathogenic biallelic Bardet–Biedl syndrome gene variants in a large population of patients with obesity."

Clinical data • P3 data • Bardet–Biedl Syndrome • Hypothalamic Injury-associated Obesity • Leptin Receptor Deficiency Obesity • Obesity • POMC-null Obesity

Paediatric Patients with Acquired Hypothalamic Obesity Treated with Setmelanotide: Real-World BMI and Hunger Data for up to 18 Months in France (Rhythm Press Release) - "-11.5% reduction in mean BMI from baseline (p<0.0001) in patients who reached 6 months (n=17); -13.4% reduction in mean BMI from baseline (p<0.001) in patients who reached 9 months (n=14); -10.5% reduction in mean BMI from baseline (p<0.01) in patients who reached 12 months (n=13); -9.0% reduction in BMI from baseline (p<0.13) in patients who reached 18 months (n=5); More than 88% of patients achieved a ≥0.2-point reduction in BMI z-score after 6, 9, or 12, and 18 months of treatment, with 100% of patients achieving ≥0.2-point reduction in BMI z-score at 12 months (n=13) and 18 months (n=5); Patient-reported hunger decreased after 6, 12, and 18 months of treatment in patients aged ≥12 to <18 years; No new safety concerns were observed and reported adverse events were consistent with Phase 3 trial data."

Real-world • Hypothalamic Injury-associated Obesity

Impact of Setmelanotide on Metabolic Index Scores in Paediatric Participants with Acquired Hypothalamic Obesity – A Phase 3 Trial Post-Hoc Analysis (Rhythm Press Release) - "Metabolic syndrome z-BMI score mean change was -0.8 vs -0.2 for the placebo group (p=0.006) (n=35 vs n=19); The mean change in Lipid Accumulation Product (LAP) (n=41 vs n=22) from baseline was -25.6 compared with +3.6 for the placebo group (p<0.0001); The mean change in Triglyceride-Glucose Waist Circumference Index (TyG-WC) (n=38 vs n=22) was -116.8 vs +34.0 for the placebo group (p<0.0001); The mean change in Visceral Adiposity Index (VAI) (n=40 vs n=22) was -1.3 vs -0.4 for the placebo group (p=0.004); The mean change in the Fatty Liver Index (FLI) (n=39 vs n=22) was -20.6 vs +6.1 for the placebo group (p<0.0001)."

P3 data • Hypothalamic Injury-associated Obesity

Impact of setmelanotide on metabolic index scores in paediatric participants with acquired hypothalamic obesity – A phase 3 trial post-hoc analysis (ESPE 2026) - No abstract available

P3 data • Retrospective data • Genetic Disorders • Hypothalamic Injury-associated Obesity • Obesity • Pediatrics

Long-term weight outcomes of setmelanotide in paediatric participants with Bardet-Biedl syndrome or with POMC or LEPR deficiency and obesity (ESPE 2026) - No abstract available

Bardet–Biedl Syndrome • Genetic Disorders • Inherited Retinal Dystrophy • Leptin Receptor Deficiency Obesity • Obesity • Ophthalmology • Pediatrics

Efficacy and Safety of Setmelanotide in Paediatric Patients With Acquired Hypothalamic Obesity: Final Phase 3 Trial Results (ESPE 2026) - No abstract available

Clinical • Late-breaking abstract • P3 data • Genetic Disorders • Hypothalamic Injury-associated Obesity • Obesity • Pediatrics

Clinical, Metabolic, and Functional Benefits of Setmelanotide in Pediatric Hypothalamic Obesity: Case Report (ESPE 2026) - No abstract available

Case report • Clinical • Genetic Disorders • Hypothalamic Injury-associated Obesity • Obesity • Pediatrics

SAT4 Advancing breakthrough therapy with setmelanotide for patients living with rare hypothalamic MC4R pathway diseases (ESPE 2026) - No abstract available

Clinical

Real-world efficacy and safety of setmelanotide in paediatric patients with Bardet-Biedl syndrome – Improvements in metabolic dysfunction-associated steatotic liver disease (MASLD) and kidney function (ESPE 2026) - No abstract available

Clinical • Real-world • Real-world effectiveness • Real-world evidence • Bardet–Biedl Syndrome • Hepatology • Inherited Retinal Dystrophy • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Ophthalmology • Pediatrics

Real world clinical outcomes of setmelanotide in Russian paediatric patients below 6 years of age with POMC deficiency (ESPE 2026) - No abstract available

Clinical • Clinical data • Real-world • Real-world evidence • Pediatrics • POMC-null Obesity

Real-World Outcomes of Setmelanotide in Children With Craniopharyngioma-Related Hypothalamic Obesity (ESPE 2026) - No abstract available

Clinical • Late-breaking abstract • Real-world • Real-world evidence • Brain Cancer • CNS Tumor • Genetic Disorders • Hypothalamic Injury-associated Obesity • Obesity

3 months Setmelanotide in Early-Onset Obesity Associated with iPPSD2 (GNAS Variants) reduces BMI and improves hunger behavior (ESPE 2026) - No abstract available

Genetic Disorders • Obesity • GNAS

Setmelanotide weight-related outcomes in two adult patients with acquired hypothalamic obesity due to craniopharyngioma under early access program (ESPE 2026) - No abstract available

Clinical • Brain Cancer • CNS Tumor • Genetic Disorders • Hypothalamic Injury-associated Obesity • Obesity

Targeted MC4R Pathway Therapy in Early Childhood: One of the Youngest Patients with LEPR Deficiency Treated with Setmelanotide (ESPE 2026) - No abstract available

Clinical • Late-breaking abstract • Leptin Receptor Deficiency Obesity

Paediatric patients with acquired hypothalamic obesity treated with setmelanotide: real-world BMI and hunger data for up to 12 months in France (ESPE 2026) - No abstract available

Clinical • Real-world • Real-world evidence • Genetic Disorders • Hypothalamic Injury-associated Obesity • Obesity • Pediatrics

Setmelanotide in ROHHAD syndrome: first experiences in a proof-of-concept study (ESPE 2026) - No abstract available

Late-breaking abstract

Targeting Obesity in ROHHAD-NET Syndrome : A Pediatric case treated with Setmelanotide (IMCIVREE®) (ESPE 2026) - No abstract available

Clinical • Genetic Disorders • Obesity • Pediatrics

Experience with Setmelanotide Use in Heterozygous Variants under Compassionate Use (ESPE 2026) - No abstract available

Genetic Disorders • Obesity

Setmelanotide in Pediatric Hypothalamic Obesity Secondary to Craniopharyngioma: Real-World Evidence from Two Cases (ESPE 2026) - No abstract available

Clinical • HEOR • Real-world • Real-world evidence • Brain Cancer • CNS Tumor • Genetic Disorders • Hypothalamic Injury-associated Obesity • Obesity • Pediatrics