EMANATE: A Study of Setmelanotide in Patients With Specific Gene Variants in the MC4R Pathway

Inclusion Criteria: * Patients must have a pre-identified: * Heterozygous genetic variant in the POMC gene or PCSK1 gene * Heterozygous genetic variant in the LEPR gene * Homozygous, heterozygous, or compound heterozygous variant in the NCOA1 (SRC1) * Homozygous, heterozygous, or compound heterozygous variant in SH2B1 gene, or chromosomal 16p11.2 deletion encompassing the SH2B1 gene * Between 6 and 65 years of age at the time of provision of informed consent/assent * Obesity, defined as BMI ≥30 kg/m2 for patients ≥18 years of age or BMI ≥95th percentile for age and gender for patients 6 up to 17 years of age * Patient and/or parent or guardian is able to understand and comply with the requirements of the study and is able to understand and sign the written informed consent/assent * Patient and/or parent or guardian reports that patient experienced childhood obesity, defined as the patient and/or parent or guardian reporting that the patient was significantly overweight during childhood * Agree to use a highly effective form of contraception throughout the study and for 90 days following the study * Reported history of lifestyle intervention of diet and exercise * Reported history of hyperphagia Key Exclusion Criteria: * Weight loss of 2% or greater in the previous 3 months * Recent history of bariatric surgery * Significant psychiatric disorder(s) * Suicidal ideation, attempt or behavior * Clinically significant pulmonary, cardiac, endocrine/metabolic, hepatic or oncologic disease * Glycated hemoglobin (HbA1C) \>10% at Screening * History of significant liver disease or severe kidney disease * History or close family history (parents or siblings) of melanoma, or patient history of oculocutaneous albinism * Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions (excluding non-invasive basal or squamous cell lesion) * Participation in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing * Previously enrolled in a clinical study involving setmelanotide or any previous exposure to setmelanotide * Significant hypersensitivity to any excipient in the study drug * If female, pregnant or breastfeeding