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

Inclusion Criteria:

1. Bi-allelic, homozygous or compound heterozygous (a different gene mutation on eachallele) genetic status for either the POMC or PCSK1 genes, with the loss-of-function (LOF) variant for each allele conferring a severe obesity phenotype.
2. Age 6 years and above.
3. If adult age ≥ 18 years, obesity with body mass index (BMI) ≥ 30 kilograms per squaremeter (kg/m^2); if child or adolescent, obesity with BMI ≥ 95th percentile for age ongrowth chart assessment.
4. Study participant and/or parent or guardian is able to communicate well with theinvestigator, to understand and comply with the requirements of the study, and be ableto understand and sign the written informed consent/assent, after being informed aboutthe study.
5. Female participants of child-bearing potential must agree to use contraception asoutlined in the protocol. Female participants of non-childbearing potential, definedas surgically sterile (status post-hysterectomy, bilateral oophorectomy, or bilateraltubal ligation) or post-menopausal for at least 12 months (and confirmed with ascreening follicular stimulating hormone [FSH] level in the post-menopausal labrange), or have delayed pubertal development and failure to have achieved menarche, donot require contraception during the study.
6. Male participants with female partners of childbearing potential must agree to adouble barrier method if they become sexually active during the study. Maleparticipants must not donate sperm during and for 90 days following theirparticipation in the study.

Exclusion Criteria:

1. Recent intensive (within 2 months) diet and/or exercise regimen with or without theuse of weight loss agents, including herbal medications, that has resulted in weightloss or weight stabilization. Participants may be reconsidered approximately 1 monthafter cessation of such intensive regimens.
2. Prior gastric bypass surgery resulting in >10% weight loss durably maintained from thebaseline pre-operative weight with no evidence of weight regain.
3. Diagnosis of schizophrenia, bipolar disorder, personality disorder or other Diagnosticand Statistical Manual of Mental Disorders (DSM-III) disorders that the investigatorbelieves will interfere significantly with study compliance.
4. A Patient Health Questionnaire-9 (PHQ-9) score of ≥ 15.
5. Any suicidal ideation of type 4 or 5 on the Columbia Suicide Severity Rating Scale (C-SSRS). Any lifetime history of a suicide attempt, or any suicidal behavior in thelast month.
6. Current, clinically significant pulmonary, cardiac, or oncologic disease.
7. History of significant liver disease or liver injury, or current liver assessment fora cause of abnormal liver tests (as indicated by abnormal liver function tests,alanine transaminase [ALT], aspartate transaminase [AST], alkaline phosphatase, orserum bilirubin [> 2.0 x upper limit of normal (ULN) for any of these tests]) for anetiology other than non-alcoholic fatty liver disease (NAFLD). Thus, any underlyingetiology besides NAFLD, including diagnosed non-alcoholic steatohepatitis (NASH),other causes of hepatitis, or history of hepatic cirrhosis will be exclusionary, butthe presence of NAFLD would not be exclusionary.
8. History or presence of impaired renal function as indicated by clinically significantabnormal creatinine, blood urea nitrogen (BUN), or urinary constituents (e.g.,albuminuria) or moderate to severe renal dysfunction as defined by the Cockcroft Gaultequation < 30 mL/min.
9. History or close family history (parents or siblings) of skin cancer or melanoma, orparticipant history of ocular-cutaneous albinism.
10. Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions,determined as part of a screening comprehensive skin evaluation performed by aqualified dermatologist.
11. Participant is, in the opinion of the study investigator, not suitable to participatein the study.
12. Participation in any clinical study with an investigational drug/device within 3months prior to the first day of dosing.
13. Significant hypersensitivity to study drug.
14. Inability to comply with every day (QD) injection regimen.