Inclusion Criteria:  Patients must have a pre-identified:  Heterozygous genetic variant in the POMC gene or PCSK1 gene (Sub-study 035a) Heterozygous genetic variant in the LEPR gene (Sub-study 035b), Homozygous, heterozygous, or compound heterozygous variant in the SRC1 (Sub-study 035c), Homozygous, heterozygous, or compound heterozygous variant in SH2B1 gene, or chromosomal 16p11.2 deletion encompassing the SH2B1 gene (Sub-study 035d), Heterozygous N221D variant in the PCSK1 gene (Sub-study 035e). 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, based on the United States (US) Centers for Disease Control and Prevention criteria. Patient and/or parent or guardian is able to communicate well with the Investigator, understand and comply with the requirements of the study (including once daily [QD] injection regimen and all other study procedures), and is able to understand and sign the written informed consent/assent. Patients who are unable to comply with all study procedures due to cognitive limitations or any other reason should not be enrolled into the study. 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. For women of child-bearing potential (WOCBP), agrees 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 (Partial list):  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 or oncologic disease that may interfere with the study and/or confound the results. 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). Patient is, in the opinion of the Study Investigator, not suitable to participate in the study. Participation in any clinical study with an investigational drug/device within 3 months or 5 half-lives, whichever is longer, 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.