This is an open-label extension study designed to evaluate the long-term safety and tolerability of continued setmelanotide treatment in male and female patients ≥2 years of age who have completed or transitioned from a previous study with setmelanotide for rare genetic, syndromic, or acquired diseases of obesity upstream of the MC4R pathway.

Key Inclusion Criteria:

• Males and females ≥2 years of age who have completed a previous setmelanotide clinical study and who have a condition or indication for which Rhythm plans further clinical development.
• Agree to use a highly effective form of contraception and follow the study contraception requirements throughout study duration and for 90 days after.
• Demonstrated clinical benefit in the previous setmelanotide study, as determined by the Investigator.

Key Exclusion Criteria:

• Any gene variant, syndromic, or acquired disease for which setmelanotide is currently approved in the United States (i.e., patients eligible for commercial setmelanotide (IMCIVREE®).
• Any new or worsening depression resulting in suicidal thoughts and/or behaviors.
• Discontinuation from a previous setmelanotide study.
• History or close family history (parents or siblings) of melanoma.
• Pregnant and/or breastfeeding women

Other protocol defined Inclusion/Exclusion criteria may apply.