Setmelanotide Yields 18.9% BMI Drop in HO, 9.8% Loss in BBS, 3.06% in PWS

RYTM•2026-06-15

Setmelanotide therapy delivered a mean 18.9% BMI reduction over 2.5 years in 11 acquired hypothalamic obesity patients, while bivamelagon yielded up to a 16.6% BMI decline at one year in 26 participants. Real-world data in 286 Bardet-Biedl syndrome patients showed a 9.8% mean weight loss with 62% of adults achieving ≥10% body weight reduction, and six-month Phase 2 Prader-Willi results in 18 patients reported a 3.06% BMI drop with consistent safety.

1. Setmelanotide Delivers 18.9% BMI Reduction in Acquired HO

In a Phase 2 study with up to 2.5 years of extension, setmelanotide achieved a mean 18.9% BMI reduction in 11 acquired hypothalamic obesity patients, lowering BMI z-scores by 1.60. Reported adverse events included nausea, skin hyperpigmentation, upper respiratory tract infections and vomiting.

2. Bivamelagon Yields Up to 16.6% BMI Loss at One Year

Oral bivamelagon produced progressive BMI reductions at one year in 26 acquired HO patients. Cohorts receiving up to 600 mg throughout saw a 16.6% decline, while hunger scores fell 1.9–4.8 points; common adverse events were vomiting, nausea, diarrhea and headache.

3. BBS Real-World Data: 9.8% Mean Weight Loss

A retrospective analysis of 286 US Bardet-Biedl syndrome patients treated with setmelanotide showed a 9.8% mean body weight loss after 12 months, with 62% of adults achieving ≥10% weight loss and a significant reduction in outpatient obesity-related visits.

4. Prader-Willi Six-Month Data Spurs 5.47% Stock Surge

Six-month Phase 2 data in 18 Prader-Willi syndrome patients demonstrated a 3.06% mean BMI reduction, improvements in hyperphagia and behavioral measures, and consistent safety in 17 active participants, triggering a 5.47% stock jump on presentation day.