Setmelanotide for the Treatment of Leptin Receptor (LEPR) Deficiency Obesity

Inclusion Criteria: 1. Bi-allelic, homozygous or compound heterozygous (a different gene mutation on each allele) genetic status for the LEPR gene, with the loss-of-function (LOF) variant for each allele conferring a severe obesity phenotype. 2. Age 6 years and above. 6+: Germany, Netherlands, UK. 12+: France 3. If adult age ≥18 years, obesity with body mass index (BMI) ≥ 30 kilograms per meters squared (kg/m\^2); if child or adolescent (\< 18 years of age), obesity with weight \> 97th percentile for age on growth chart assessment. 4. Study participant and/or parent or guardian is able to communicate well with the investigator, to understand and comply with the requirements of the study, and is able to understand and sign the written informed consent/assent, after being informed about the study. 5. Female participants of child-bearing potential must agree to use contraception as outlined in the protocol. Female participants of non-childbearing potential, defined as surgically sterile (status post hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) post-menopausal for at least 12 months (and confirmed with a screening FSH level in the post-menopausal lab range), or failure to have progressed to Tanner Stage V and/or failure to have achieved menarche, do not require contraception during the study. 6. Male participants with female partners of childbearing potential must agree to a double barrier method if they become sexually active during the study. Male participants must not donate sperm during and for 90 days following their participation in the study. Exclusion Criteria: 1. Recent intensive (within 2 months) diet and/or exercise regimen with or without the use of weight loss agents including herbal medications, that has resulted in weight loss or weight stabilization. 2. Prior gastric bypass surgery resulting in \>10% weight loss durably maintained from the baseline pre-operative weight with no evidence of weight regain. 3. Diagnosis of schizophrenia, bipolar disorder, personality disorder or other Diagnostic and Statistical Manual of Mental Disorders (DSM-III) disorders that the investigator believes 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 the last month. 6. Current, severe stable restrictive or obstructive lung disease arising because of extreme obesity, evidence of significant heart failure (New York Heart Association \[NYHA\] Class 3 or greater), or oncologic disease, if these were severe enough to interfere with the study and/or would confound the results. 7. History of significant liver disease or liver injury, or current liver assessment for a cause of abnormal liver tests \[as indicated by abnormal liver function tests, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase, or serum bilirubin (\> 2.0 x upper limit of normal (ULN) for any of these tests)\] for an etiology other than non-alcoholic fatty liver disease (NAFLD). 8. History or presence of impaired renal function as indicated by clinically significant abnormal creatinine, blood urea nitrogen (BUN), or urinary constituents (e.g., albuminuria) or moderate to severe renal dysfunction as defined by the Cockcroft Gault equation \< 30 milliliter/minute (mL/min). 9. History or close family history (parents or siblings) of skin cancer or melanoma, or participant 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 a qualified dermatologist. 11. Volunteer is, in the opinion of the study investigator, not suitable to participate in the study. 12. Participation in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing. 13. Significant hypersensitivity to study drug. 14. Inability to comply with every day (QD) injection regimen. 15. Participants who have been placed in an institution through an official or court order, as well as those who are dependent on the sponsor, Investigator or study site.