The investigators plan to test the efficacy and safey of 6-months of open-label setmelanotide to treat obesity in a single patient with pseudohypoparathyroidism type 1a due to a GNAS mutation.

This is a sub-study of Study RM-493-040 (NCT05774756). The goal of this sub-study is to learn how well Setmelanotide works to improve weight reduction, hunger, and quality of life in patients 4 years of age and older with congenital Hypothalamic Obesity (cHO). To determine how well setmelanotide works and how safe it is, patients with cHO will take a daily injection of either setmelanotide or placebo and complete trial assessments for up to 26 weeks on a therapeutic regimen.

Bardet-Biedl syndrome (BBS) and other rare disorders associated with impairment of the melanocortin-4 receptor (MC4R) pathway are characterized by severe early-onset obesity, hyperphagia, and substantial morbidity. Setmelanotide, an MC4R agonist, is approved in Europe for selected genetic obesity disorders and reimbursed in Germany for eligible patients. This study aims to evaluate the effectiveness, safety, treatment persistence, metabolic outcomes, and patient-reported outcomes of Setmelanotide under real-world conditions. The registry is designed to allow future inclusion of additional MC4R…

This is a Phase 2, open-label study designed to assess the safety and efficacy of setmelanotide in patients with obesity due to Prader-Willi Syndrome (PWS) who are 6 to 65 years of age. Up to 20 patients are planned to be enrolled. Patients will take a daily subcutaneous dose of open-label setmelanotide for up to 52 weeks.

The goal of this trial is to learn how well Setmelanotide works to improve weight reduction, hunger, and quality of life in patients 4 years of age and older with acquired Hypothalamic Obesity (HO). To determine how well setmelanotide works and how safe it is, patients with HO will take a daily injection of either setmelanotide or placebo and complete trial assessments for 52 weeks on a therapeutic regimen. A separate sub-study in patients with congenital HO is detailed under NCT06760546.

The purpose of the study was to determine the effect of setmelanotide (RM-493) on weight, hunger assessments, and other factors in participants with rare genetic disorders of obesity.

This was a long-term extension trial to study the safety and tolerability of continued setmelanotide treatment in participants who had completed a previous clinical trial on treatment with setmelanotide for obesity associated with genetic defects upstream of the Melanocortin-4 (MC4) receptor in the leptin-melanocortin pathway.

The purpose of this study was to evaluate the safety and efficacy of once daily subcutaneous (SC) administration of setmelanotide in participants with obesity and specific gene variants in the MC4R pathway.

The purpose of this study is to evaluate the effects of a new daily subcutaneous (SC) injectable formulation of setmelanotide (RM-493) in healthy participants with obesity on mean percent body weight loss and other weight loss parameters, as well as pharmacokinetic (PK) profile. The study is designed to evaluate the efficacy and tolerability of setmelanotide administered once or twice daily. The study drug (setmelanotide and placebo) will be administered in a blinded fashion.

This was a double-blind, randomized, placebo- and positive-controlled, parallel group, 3-arm study that assessed the potential for therapeutic and supratherapeutic concentrations of setmelanotide to affect the QTc corrected by the Fredericia method (QTcF) interval.

The purpose of this study is to evaluate the effects of RM-493 on mean percent body weight loss, and other weight loss parameters as well as Pharmacokinetic (PK) profile, and ambulatory blood pressure in obese participants. The study is designed to evaluate the efficacy and tolerability of a single dose of RM-493. The study drug (RM-493 and placebo) will be administered subcutaneously in a blinded fashion.

This pivotal, phase 3 study is designed to confirm the efficacy and safety of setmelanotide, a potent melanocortin receptor type 4 (MC4R) agonist, for the treatment of obesity and hyperphagia in participants with Bardet Biedl syndrome (BBS) or Alström syndrome (AS). The study's primary efficacy endpoint is to evaluate the proportion of participants (≥ 12 years of age at baseline) who lose ≥ 10% of their baseline body weight following approximately (\~) 52 weeks of treatment with setmelanotide compared to a historical control rate.

The purpose of this study was to evaluate the effects of a once daily subcutaneous injectable formulation of setmelanotide in obese participants with Prader-Willi syndrome on tolerability, weight loss, and hyperphagia-related behavior. The study drug (setmelanotide and placebo) was administered in a blinded fashion.

A trial to compare the weekly and daily formulations of setmelanotide in participants with genetic defects in the melanocortin-4 receptor pathway.

Open-label, single-arm study designed to evaluate the body weight response to setmelanotide administered subcutaneously (SC) daily in participants with hypothalamic obesity (HO).

To demonstrate statistically significant and clinically meaningful effects of setmelanotide on percent body weight change in participants with LEPR deficiency obesity due to rare bi-allelic or loss-of function mutations at the end of 1 year of treatment.

To demonstrate statistically significant and clinically meaningful effects of setmelanotide on percent body weight change in participants with pro-opiomelanocortin (POMC) deficiency or proprotein convertase subtilisin/kexin type 1 (PCSK1) deficiency obesity due to rare biallelic or loss-of function mutations at the end of 1 year of treatment.

This is a phase 3 open-label, clinical study to evaluate the efficacy, safety and tolerability of setmelanotide over 1 year of treatment, in pediatric participants aged 2 to \<6 years with obesity due to either biallelic variants of the pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1) or leptin receptor (LEPR) genes or Bardet-Biedl Syndrome (BBS).

The protocol describes a randomized, double-blind, placebo-controlled trial with independent sub-studies of setmelanotide in patients with obesity and at least one of the specific gene variants in the Melanocortin-4 Receptor pathway: * POMC or PCSK1 (Sub-study 035a) * LEPR (Sub-study 035b) * SRC1 (Sub-study 035c) * SH2B1 (Sub-study 035d) The objectives and endpoints are identical for these sub-studies.

The purpose of this study is to evaluate the multiple dose safety and tolerability of RM-493 (setmelanotide) as well as pharmacokinetic (PK) and pharmacodynamic (PD; weight loss) profile, in healthy obese patients for 2 to 4 weeks. In addition, one panel of patients with a specific genetic deficiency in the hypothalamic leptin- proopiomelanocortin (POMC) - melanocortin-4 receptor (MC4R) pathway, those with heterozygous partial or full loss of function (LOF) of the MC4R gene, will also be studied. The study drug (RM-493 and placebo) will be administered subcutaneously in a blinded fashion by su…

This is a Phase 1, multi-center, open-label, single-dose study designed to assess the effect of renal impairment on the PK of setmelanotide. A total of approximately 32 subjects (approximately 8 subjects in each renal impairment group and 8 healthy subjects with normal renal function) are planned to be enrolled across 4 centers in the United States. At screening, subjects will be assigned to a study group according to eGFR. Cohort A - Mild Renal Impairment Cohort B - Moderate Renal Impairment Cohort C - Severe Renal Impairment Cohort D - Normal Renal Function (control)

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.

Background: \- RM-493 is a drug that stimulates parts of the brain that control eating and metabolism. It has helped to reduce body weight and improve insulin sensitivity in lab tests. However, it is not fully known whether RM-493 causes weight loss by just decreasing appetite or by increasing metabolism or both. Researchers want to see how RM-493 affects metabolism and hormones that affect the metabolic rate. They also want to see how RM-493 affects appetite by assessing feelings of hunger and fullness. They will study this drug in people who are obese but are otherwise in good health. Obje…

The objective of this single patient study is to assess the safety and efficacy of setmelanotide as a treatment of severe metabolic abnormalities resulting from LD, especially refractory hypertriglyceridemia leading to recurrent bouts of pancreatitis.

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.

An open-label, single-arm, multicenter, Expanded Access Protocol \[EAP\] designed to provide treatment access to setmelanotide (3 mg, administered subcutaneously \[SC\], once daily) for eligible patients with BBS who have no alternative treatment options. All patients will continue to receive setmelanotide at the discretion of the Treating Physician and while they are deriving clinical benefit.