Setmelanotide for the Treatment of Early-Onset Pro-Opiomelanocortin (POMC) Deficiency Obesity

Percentage of Participants Who Reached ≥10% Weight Loss Threshold After 1 Year (Pivotal Cohort)

Time frame · Week 52

The percentage of participants who met the ≥ 10% weight loss threshold after approximately Week 52 (\~1 year) of treatment were analyzed.

Percentage of Participants Who Reached ≥10% Weight Loss Threshold After 1 Year (Pivotal + Supplemental Cohort)

Time frame · Week 52

The percentage of participants who met the ≥ 10% weight loss threshold after approximately Week 52 (\~1 year) of treatment were analyzed.

Mean Percent Change From Baseline in Body Weight at Week 52

Time frame · Baseline, Week 52

The mean percent change from baseline in body weight at 52 weeks was analyzed.

Mean Percent Change From Baseline in Hunger Score (Worst "Most" Hunger in 24 Hours) at Week 52

Time frame · Baseline, Week 52

The mean percent change in hunger scores for participants ≥12 years of age with leptin receptor (LEPR) deficiency obesity in treatment with setmelanotide was evaluated. Hunger score ranged from 0 - 10 on a Likert-type scale; 0 = not hungry at all and 10 = hungriest possible. On the Daily Hunger Questionnaire, each of the 3 items (average hunger, most/worst hunger, and morning hunger) was scored separately and averaged on a weekly basis. The weekly average hunger score of the daily worst (most) hunger score in 24 hours is the hunger score used to assess this study endpoint.

Percentage of Participants Who Achieved at Least 25% Improvement in Daily Hunger From Baseline

Time frame · Baseline, Week 52

The percentage of participants (≥12 years of age) achieving a ≥25% improvement from baseline in hunger score at Week 52 (i.e., after treatment with setmelanotide for 52 weeks at the therapeutic dose) was assessed. Hunger ranged from 0 - 10 on a Likert-type scale; 0 = not hungry at all and 10 = hungriest possible. On the Daily Hunger Questionnaire, each of the 3 items (average hunger, most/worst hunger, and morning hunger) was scored separately and averaged on a weekly basis. The weekly average hunger score of the daily worst (most) hunger score in 24 hours is the hunger score used to assess this study endpoint.

Absolute Change From Baseline in Waist Circumference at Week 52

Time frame · Baseline, Week 52

Waist circumference (centimeters) was measured according to the National Heart, Lung, and Blood Institute (NHLBI) criteria. Waist circumference was measured when participants were fasting at approximately the same time at each visit. The absolute change from baseline in waist circumference was assessed.

Absolute Change in Body Weight (Reversal of Weight Loss) During Double-Blind Placebo-Controlled Withdrawal Period

Time frame · Baseline, 8-week withdrawal period (up to ~Week 20)

A comparison of weight change was evaluated during the 8 week placebo-controlled withdrawal period for each participant, during which each participant received 4 weeks of placebo and 4 weeks active therapy in a blinded fashion.

Absolute Score in Daily Hunger Reduction During the Double-Blind Placebo-Controlled Withdrawal Period

Time frame · 8-week withdrawal period (up to ~Week 20)

The absolute score in daily hunger during the double-blind placebo-controlled withdrawal period (≥12 Years of Age) was assessed. Hunger ranged from 0 - 10 on a Likert-type scale; 0 = not hungry at all and 10 = hungriest possible. On the Daily Hunger Questionnaire, each of the 3 items (average hunger, most/worst hunger, and morning hunger) was scored separately and averaged on a weekly basis. The weekly average hunger score of the daily worst (most) hunger score in 24 hours is the hunger score used to assess this study endpoint. Lower scores represent lower hunger, higher scores represent greater hunger.

Mean Percent Change From Baseline in Body Mass Index (BMI) at Week 52

Time frame · Baseline, Week 52

The mean percent change from baseline in BMI was assessed.

Area Under the Curve (AUC) Change From Baseline in Oral Glucose, Assessed by the Oral Glucose Tolerance Test (OGTT)

Time frame · Baseline, Week 52

The AUC change from baseline for the OGTT was assessed. The AUC was calculated by the linear trapezoidal method and includes pre-dose and post-dose assessments. At each visit, oral glucose was captured pre-meal, and post-meal at the following times: 30 minutes, 60 minutes, 90 minutes, and 120 minutes. OGTT was not performed for participants with a diagnosis of Type 1 or Type 2 diabetes.

Change From Baseline in Serum Glucose at Week 52

Time frame · Baseline, Week 52

Change from baseline in serum glucose at Week 52 was assessed.