A Trial of Setmelanotide in Acquired Hypothalamic Obesity

Pivotal Cohort: Mean Percent Change From Baseline in Body Mass Index (BMI) After 52 Weeks on a Therapeutic Regimen

Time frame · Baseline, after approximately 52 Weeks on a Therapeutic Regimen (up to approximately 60 weeks)

BMI was calculated as weight (kg)/height (m\^2). Least square (LS) mean and standard error (SE) were calculated using analysis of covariance (ANCOVA) model.

Pivotal Cohort: Percentage of Participants With ≥5% Reduction From Baseline in BMI (≥18 Years of Age) or ≥0.2-point Reduction From Baseline in BMI Z-score (<18 Years of Age)

Time frame · After approximately 52 Weeks on a Therapeutic Regimen (baseline up to approximately 60 weeks)

BMI was calculated as weight (kg)/height (m\^2). BMI Z-Score calculated for participants \<18 years old only is a measure of relative weight adjusted for child's age, sex and height at the time of data collection. The Z-Scores were calculated using the World Health Organization's WHO 2007 BMI SAS Macro Package. A Z-score of 0 is equal to the mean of a reference population (i.e., healthy, age and sex-matched individuals). A decrease in BMI Z-score (\< 0) indicates a reduction in BMI from Baseline whereas an increase in BMI-Z score (\> 0) indicated an increase in BMI from Baseline. Baseline was defined as the most recent measurement prior to the first administration of study drug. Results below represent the percentage of estimated participants with either ≥5% BMI reduction or ≥0.2 point reduction in BMI Z-score by age in each treatment arm as calculated through the MIANALYZE SAS procedure.

Pivotal Cohort: Percentage of Participants With ≥5% Reduction From Baseline in BMI

Time frame · After approximately 52 Weeks on a Therapeutic Regimen (baseline up to approximately 60 weeks)

BMI was calculated as weight (kg)/height (m\^2). Results below represent the percentage of estimated participants with ≥5% BMI reduction in each treatment arm as calculated through the MIANALYZE SAS procedure.

Pivotal Cohort: Change From Baseline in Weekly Average Daily Most Hunger Score in Participants ≥12 Years of Age

Time frame · Baseline, after approximately 52 Weeks on a Therapeutic Regimen (up to approximately 60 weeks)

Change from baseline in hunger scores for participants ≥12 years of age with acquired hypothalamic obesity was evaluated. Hunger score ranged from 0= "not hungry at all" to 10= "hungriest possible" on an 11-point numeric rating scale. On Daily Hunger Questionnaire, each of the 2 items (average hunger and most hunger) was scored separately and averaged on weekly basis. LSM and SE were calculated using ANCOVA model.

Pivotal Cohort: Percentage of Participants (≥12 Years of Age) With a ≥2-point Reduction From Baseline in the Weekly Average Daily Most Hunger Score

Time frame · After approximately 52 Weeks on a Therapeutic Regimen (baseline up to approximately 60 weeks)

Hunger score ranged from 0= "not hungry at all" to 10= "hungriest possible" on an 11-point numeric rating scale. On Daily Hunger Questionnaire, each of the 2 items (average hunger and most hunger) was scored separately and averaged on weekly basis. Results below represent the percentage of estimated participants ≥12 years of age with ≥2-point reduction in each treatment arm as calculated through the MIANALYZE SAS procedure.

Pivotal Cohort: Mean Change From Baseline in the Weekly Average of the Symptoms of Hyperphagia Composite Score in Participants ≥12 Years of Age

Time frame · Baseline, after approximately 52 Weeks on a Therapeutic Regimen (up to approximately 60 weeks)

Participants ≥12 years of age who were able to self-report were administered the Symptoms of Hyperphagia: Patient (Version 1.0). The questionnaire consisted of 4 items related to the frequency of a participant's hunger symptoms on a scale (Never, 1 or 2 times, 3 or more times) over the past 24 hours. The scores on this scale range from 0 to 2 with higher scores indicating more hyperphagia. Daily composite score was derived as the sum of daily answered questions divided by the number of answered questions per day. The weekly average of the daily composite scores equals to the sum of daily composite scores divided by the number of days with a composite score within the 7 identified days prior to the visit. LSM and SE were calculated using ANCOVA model.

Pivotal Cohort: Percentage of Participants With a ≥10% Reduction From Baseline in BMI

Time frame · After approximately 52 Weeks on a Therapeutic Regimen (baseline up to approximately 60 weeks)

BMI was calculated as weight (kg)/height (m\^2). Results below represent the percentage of estimated participants with ≥10% BMI reduction in each treatment arm as calculated through the MIANALYZE SAS procedure.

Pivotal Cohort: Percentage of Participants With a ≥10% Reduction From Baseline in Body Weight

Time frame · After approximately 52 Weeks on a Therapeutic Regimen (baseline up to approximately 60 weeks)

Body weight was captured for analysis in kilograms. Results below represent the percentage of estimated participants with ≥10% reduction in body weight in each treatment arm as calculated through the MIANALYZE SAS procedure.

Pivotal Cohort: Mean Percent Change From Baseline in Body Weight in Participants ≥18 Years

Time frame · Baseline, after approximately 52 Weeks on a Therapeutic Regimen (up to approximately 60 weeks)

Body weight was captured for analysis in kilograms. LSM and SE were calculated using ANCOVA model.

Pivotal Cohort: Mean Change From Baseline in BMI Z-Score in Participants <18 Years of Age

Time frame · Baseline, after approximately 52 Weeks on a Therapeutic Regimen (up to approximately 60 weeks)

BMI was calculated as weight (kg)/height (m\^2). BMI Z-Score calculated for participants \<18 years old only is a measure of relative weight adjusted for child's age, sex and height at the time of data collection. The Z-Scores were calculated using the World Health Organization's WHO 2007 BMI SAS Macro Package. A Z-score of 0 is equal to the mean of a reference population (i.e., healthy, age and sex-matched individuals). A decrease in BMI Z-score (\< 0) indicates a reduction in BMI from Baseline whereas an increase in BMI-Z score (\> 0) indicates an increase in BMI from Baseline. Baseline was defined as the most recent measurement prior to the first administration of study drug. LSM and SE were calculated using ANCOVA model.

Pivotal Cohort: Mean Change From Baseline in Percent of BMI 95th Percentile in Participants <18 Years of Age

Time frame · Baseline, after approximately 52 Weeks on a Therapeutic Regimen (up to approximately 60 weeks)

BMI was calculated using participant's weight and height assessments, using the following formula: BMI = kg/m\^2. BMI percentile scores are measures of relative weight adjusted for child's age and gender. The percent of the BMI 95th percentile score expresses the participant's BMI as a percentage of the Centers for Disease Control (CDC) 95th percentile reference population. Baseline was defined as the most recent measurement prior to the first administration of study drug. LSM and SE were calculated using ANCOVA model.