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

Inclusion Criteria:

Patients must have a pre-identified:

1. Heterozygous genetic variant in the POMC gene or PCSK1 gene
2. Heterozygous genetic variant in the LEPR gene
3. Homozygous, heterozygous, or compound heterozygous variant in the NCOA1 (SRC1)
4. Homozygous, heterozygous, or compound heterozygous variant in SH2B1 gene, or chromosomal 16p11.2 deletion encompassing the SH2B1 gene
5. Between 6 and 65 years of age at the time of provision of informed consent/assent
6. 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
7. 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
8. 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
9. Agree to use a highly effective form of contraception throughout the study and for 90 days following the study
10. Reported history of lifestyle intervention of diet and exercise
11. Reported history of hyperphagia

Key Exclusion Criteria:

1. Weight loss of 2% or greater in the previous 3 months
2. Recent history of bariatric surgery
3. Significant psychiatric disorder(s)
4. Suicidal ideation, attempt or behavior
5. Clinically significant pulmonary, cardiac, endocrine/metabolic, hepatic or oncologic disease
6. Glycated hemoglobin (HbA1C) >10% at Screening
7. History of significant liver disease or severe kidney disease
8. History or close family history (parents or siblings) of melanoma, or patient history of oculocutaneous albinism
9. Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions (excluding non-invasive basal or squamous cell lesion)
10. Participation in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing
11. Previously enrolled in a clinical study involving setmelanotide or any previous exposure to setmelanotide
12. Significant hypersensitivity to any excipient in the study drug
13. If female, pregnant or breastfeeding