Rhythm Pharma setmelanotide shows BMI gains in paediatric HO data
Rhythm Pharmaceuticals presented six data readouts at the 64th Annual European Society for Paediatric Endocrinology (ESPE) meeting in Marseille this week, adding real-world weight and hunger data to the Phase 3 TRANSCEND trial evidence base for its MC4R agonist setmelanotide (IMCIVREE) in paediatric acquired hypothalamic obesity (HO).
The real-world analysis drew on France's early-access programme and followed 30 paediatric patients aged 6 to 17 with acquired HO for up to 18 months. Mean BMI fell 11.5% from baseline at six months (p less than 0.0001, n=17) and 13.4% at nine months (p less than 0.001, n=14). At 12 months, with 13 evaluable patients, mean BMI was 10.5% below baseline (p less than 0.01). The 18-month cohort was small at five patients and the reduction of 9.0% did not reach conventional statistical significance (p=0.13). More than 88% of patients achieved a clinically meaningful BMI z-score reduction of at least 0.2 points across all assessed timepoints, with 100% of the 12- and 18-month cohorts hitting that threshold. Patient-reported hunger also declined among adolescents aged 12 and older. No new safety signals emerged.
Cardiometabolic signals from TRANSCEND post-hoc
A separate post-hoc analysis of the Phase 3 TRANSCEND trial examined composite cardiometabolic risk indices in the same population. Across four validated measures, setmelanotide consistently outperformed placebo. The Lipid Accumulation Product fell by 25.6 points versus a gain of 3.6 in the placebo group (p less than 0.0001); the Triglyceride-Glucose Waist Circumference Index dropped 116.8 units versus a placebo increase of 34.0 (p less than 0.0001); the Fatty Liver Index declined 20.6 points versus a gain of 6.1 (p less than 0.0001); and the Visceral Adiposity Index fell 1.3 versus 0.4 in the placebo arm (p=0.004). The metabolic syndrome z-BMI score also improved significantly versus placebo (p=0.006).
"Real-world data from France show that setmelanotide is associated with sustained improvements in BMI and hunger for up to 18 months," said David Meeker, chairman, chief executive and president of Rhythm Pharmaceuticals. "Together with data from our Phase 3 TRANSCEND trial demonstrating improvements across multiple cardiometabolic risk measures, these findings provide a more comprehensive picture of the treatment's impact in acquired hypothalamic obesity."
Market context and regulatory backdrop
Setmelanotide holds FDA approval for acquired HO as well as for obesity linked to Bardet-Biedl syndrome, POMC deficiency and LEPR deficiency. The European Commission and UK MHRA have both authorised the drug across the same indications. That triple-market approval base is relatively rare for a drug targeting MC4R pathway diseases, which individually affect small patient populations but together represent a commercially meaningful rare-disease franchise.
The broader rare paediatric obesity space remains thinly populated by approved agents. Outside setmelanotide, clinicians managing acquired HO, which typically follows damage to the hypothalamus from tumours such as craniopharyngioma or from their surgical treatment, have few pharmacological options beyond lifestyle intervention and off-label use of agents developed for common obesity. That unmet need has been the central plank of Rhythm's commercial positioning since IMCIVREE's initial approval in 2020.
The ESPE presentations also included five-year weight outcome data in patients with POMC or LEPR deficiency or Bardet-Biedl syndrome, and two analyses of the genetic and clinical features of BBS in large cohorts. Together, the dataset reinforces Rhythm's strategy of building a durable evidence base across its approved indications ahead of potential label expansions and competition from pipeline MC4R-targeting programmes at other companies. Rhythm is also advancing two investigational MC4R agonists, bivamelagon and RM-718, which could eventually broaden the company's reach into adjacent rare neuroendocrine conditions.