Inclusion Criteria:  Patients must have obesity due to either:  POMC, PCSK1, or LEPR deficiency, confirmed by genetic testing demonstrating biallelic variants that are interpreted as pathogenic, likely pathogenic, or of undetermined significance (VUS) by the American College of Medical Genetics and Genomics (ACMG) criteria, or BBS as defined by both (1) the Beales Criteria, 1999 (Beales 1999 [Appendix 16.1]) AND (2) genetic confirmation of homozygous or compound heterozygous loss-of-function mutation in BBS genes. Age between 2 to <6 years at the time of informed consent are eligible for the study. Obese, defined as body mass index (BMI) ≥97th percentile for age and gender AND body weight of at least 20 kg at the time of enrollment Parent or guardian of study participant is able to communicate well with the PI, to 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 consent.  Exclusion Criteria:  HbA1c >9.0% at screening History of significant liver disease other than non-alcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH). Glomerular filtration rate (GFR) <60 mL/min 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), determined as part of a comprehensive skin evaluation performed by the PI during screening. Any concerning lesions identified during screening will be biopsied and results known to be benign prior to enrollment. If the pre-treatment biopsy results are of concern, the patient may need to be excluded from the study. Patient is, in the opinion of the Study PI, not suitable to participate in the study. 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. Inadequate hepatic function as evidenced by elevated Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) values >5 Upper limit of normal (ULN).