Announcement • Jun 15
Rhythm Pharmaceuticals Presents Interim Six-Month Data from Phase 2 Trial of Setmelanotide in Patients with Prader-Willi Syndrome
Rhythm Pharmaceuticals announced preliminary data from a Phase 2 trial evaluating setmelanotide in patients with Prader-Willi syndrome (PWS) delivered during the Endocrine Society’s Annual Meeting (ENDO 2026) in Chicago. Rhythm enrolled 18 patients with PWS aged 6-23 years old with a BMI =30 kg/m2 for patients =18 years of age or BMI =95th percentile for age and sex for patients younger than 18 in this Phase 2 trial. The 52-week trial remains ongoing, and 17 patients remain on active therapy as of June 12, 2026. Results from the six-month analysis demonstrate that treatment with setmelanotide was associated with improvements across multiple clinically relevant endpoints, as of a data cut off date of May 7, 2026. Highlights include: Consistent BMI reductions in pediatric and adult patients at Month 6: -3.06% mean reduction in BMI (N=17 pts); -3.11% mean reduction in BMI in adult patients (n=10); with six achieving >2.5% BMI reduction, and four achieving >4% BMI reduction; -3.00% mean reduction in BMI in pediatric patients (n=7); -0.35 mean reduction in BMI z-score from baseline in pediatric patients (n=7); Five (5) of seven pediatric patients achieved clinically meaningful BMI z-score reduction >0.2; Setmelanotide achieved preservation of lean mass and reductions in fat mass across 16 patients with data available from DEXA scans: +0.74% mean gain in lean mass and -4.19% mean loss in fat mass across 16 patients; Six (6) of nine adult patients achieved >5% reduction in fat mass; Five (5) of seven pediatric patients gained =2.95% in lean mass; Clinically meaningful improvement in hyperphagia score observed in patients with moderate to severe hyperphagia, defined as a =7-point reduction in Hyperphagia Questionnaire for Clinical Trials (HQ-CT) score. Eight (8) of 10 patients who entered trial with moderate to severe hyperphagia (>13 at baseline) achieved clinically meaningful improvement of 7 points or better. Improvement in PWS Anxiousness and Distress Behaviors Questionnaire (PADQ) which measures anxiousness, emotional distress, and behavioral dysregulation. Of the 15 patients who had a baseline score >11, 10 patients achieved clinically meaningful improvement of =11 points; and Safety and tolerability results have been consistent with the well-established profile observed with setmelanotide. Setmelanotide is an MC4R agonist designed to treat hyperphagia and severe obesity, and is approved by the U.S. Food and Drug Administration (FDA) to reduce excess body weight and maintain weight reduction long term in adult and pediatric patients aged 4 years and older with acquired hypothalamic obesity, adult and pediatric patients 2 years of age and older with syndromic or monogenic obesity due to Bardet-Biedl syndrome (BBS) or genetically confirmed pro-opiomelanocortin (POMC), including proprotein convertase subtilisin/kexin type 1 (PCSK1), deficiency or leptin receptor (LEPR) deficiency. The European Commission (EC) has authorized setmelanotide for the treatment of obesity and control of hunger in patients 4 years of age and above with acquired hypothalamic obesity; and both the EC and the UK’s Medicines & Healthcare Products Regulatory Agency (MHRA) have authorized setmelanotide for the treatment of obesity and the control of hunger associated with genetically confirmed BBS or genetically confirmed loss-of-function biallelic POMC, including PCSK1, deficiency or biallelic LEPR deficiency in adults and children 2 years of age and above. Additionally, Rhythm is advancing a broad clinical development program for setmelanotide in other rare diseases, as well as investigational MC4R agonists bivamelagon and RM-718, and a preclinical suite of small molecules for the treatment of congenital hyperinsulinism. In the United States, setmelanotide is indicated to reduce excess body weight and maintain weight reduction long term in adults and pediatric patients aged 4 years and older with acquired hypothalamic obesity, in adult and pediatric patients aged 2 years and older with syndromic or monogenic obesity due to Bardet-Biedl syndrome (BBS) or Pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS). In the European Union and the United Kingdom, setmelanotide is indicated for the treatment of obesity and the control of hunger associated with genetically confirmed BBS or loss-of-function biallelic POMC, including PCSK1, deficiency or biallelic LEPR deficiency in adults and children 2 years of age and above. In the European Union and the United Kingdom, setmelanotide should be prescribed and supervised by a physician with expertise in obesity with underlying genetic etiology. Setmelanotide is not indicated for the treatment of patients with the following conditions as setmelanotide would not be expected to be effective: Obesity due to suspected POMC, PCSK1, or LEPR deficiency with POMC, PCSK1, or LEPR variants classified as benign or likely benign; Other types of obesity not related to acquired HO, BBS, or POMC, PCSK1 or LEPR deficiency, including obesity associated with other genetic syndromes and general (polygenic) obesity. Contraindications include prior serious hypersensitivity to setmelanotide or any of the excipients in IMCIVREE. Warnings and precautions include disturbance in sexual arousal, depression and suicidal ideation, hypersensitivity reactions, skin hyperpigmentation, darkening of pre-existing nevi, and development of new melanocytic nevi, acute adrenal insufficiency with acquired HO, sodium imbalance in patients with acquired HO and central diabetes insipidus. Most common adverse reactions (incidence =20% in at least 1 indication) included skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection. Treatment with IMCIVREE is not recommended when breastfeeding. Discontinue IMCIVREE when pregnancy is recognized unless the benefits of therapy outweigh the potential risks to the fetus.
