The purpose of this study is to evaluate the effects of a once daily subcutaneous (SC) injection of RM-493, in subjects with POMC (propiomelanocortin) or other related rare genetic mutations, on body weight, metabolic function and blood pressure. Patients who respond during the initial 84 days of treatment can enter into long-term (2-year) extensions. The study drug (RM-493) will be administered in an unblinded fashion.

Inclusion Criteria:

• Written informed consent

• Homozygous or compound heterozygous (different gene mutation on both alleles) POMC, LEPR or PCSK1 gene mutation

• Obesity (BMI > 30 kg/m2; + 2 BMI SDS)

• No other therapeutic option, which might cure the patient (e.g. bariatric surgery (see chapter 8))

• Negative Pregnancy test

• Highly effective contraception in women (defined as pearl index < 1), if necessary also for partners of test persons)

• No participation in other clinical trials according to AMG (Arzneimittelgesetz) (2 months before and after) at the time of this trial

• Normal or minimally elevated blood pressure (measured in 24RR monitoring or similar methods) according the guidelines of the ESH (European Society of Hypertension) and Deutsche Hochdruckliga: systolic > 159 mmHg/diastolic 99 mmHg

• sufficient kidney and liver function (Creatinine, ALT, AST)

  • normal values Alanine-Aminotransferase (ALT) (female): < 31 U/l
  • normal values Alanine-Aminotransferase (ALT) (male): < 41 U/l
  • normal values Aspartate-Aminotransferase (AST) (female > 17 years): < 35 U/l; (female < 17 years): 16- 46 U/l
  • normal values Aspartate-Aminotransferase (AST) (male > 17 years): < 50 U/l; (male < 17 years): 16-46 U/l
  • normal values bilirubins (male and female) up to 1,2 mg/dl
  • normal values Creatinine (female > 15 years): 0,51-0,95 mg/dl) ; (female < 15 years): 0,46-0,77 mg/dl
  • normal values Creatinine (male > 15 years): 0,67 - 1,17 mg/dl) ; (male < 15 years): 0,46-0,77 mg/dl

Exclusion Criteria:

• Pregnancy or Breastfeeding
• All contraindications against study medication (including auxiliary substances)
• Interactions with study medication
• Participation of the patient in a clinical study within the last 2 months
• Intolerance against albumin
• Concomitant diseases, impaired organ functions, except for known, concurrent GI disorders or other clinical findings expected in PCSK1 or LEPR gene disorders
• Renal insufficiency (Creatinine > 0,95 mg/dl (female), > 1,17 mg/dl (male))
• Impaired liver function (Bilirubins > 1.2 mg/dl)
• Neurological / psychiatric diseases
• HIV Infection
• Active Hepatitis B or C
• Melanoma or Melanoma occurrence in the family history
• Non-compliance
• Subjects who are legally detained in an official institution