The Food and Drug Administration (FDA) has accepted for Priority Review the supplemental New Drug Application for setmelanotide for the treatment of patients 6 years of age and older with Bardet-Biedl syndrome (BBS) and Alström syndrome.

Bardet-Biedl syndrome (BBS) and Alström syndrome are rare genetic disorders that affect multiple organ systems. The common feature for both of these diseases is hyperphagia, which is believed to be related to impaired signaling via the melanocortin 4 receptor (MC4R) pathway in the hypothalamus. Setmelanotide is a MC4R agonist that re-establishes MC4 receptor pathway activity to reduce hunger and promote weight loss through decreased caloric intake and increased energy expenditure. 

The application is supported by data from a phase 3 study ( Identifier: NCT03746522) that evaluated the efficacy and safety of setmelanotide for the treatment of obesity and hyperphagia in patients 6 years of age and older with BBS and Alström syndrome. Patients were randomly assigned to receive either setmelanotide or placebo for 14 weeks, followed by an open-label treatment period in which all patients received setmelanotide for 38 weeks.

The primary endpoint was the proportion of patients 12 years and older at baseline who achieved greater than or equal to 10% reduction in body weight after 52 weeks of treatment with setmelanotide.

Results showed that among 31 evaluable patients (28 with BBS and 3 with Alström syndrome), 34.5% (n=11/31) achieved a 10% reduction in body weight at approximately 52 weeks of therapy (P =.0024); this included 11 of 28 patients with BBS and 0 of 3 patients with Alström syndrome. Setmelanotide was also associated with a 6.2% mean reduction in body weight (P <.0001) and a 30.8% mean reduction in most hunger rating (P <.0001); 60.2% of patients achieved at least 25% reduction in most hunger scores from baseline at approximately 52 weeks (P <.0001).

As for safety, setmelanotide was generally well tolerated with no treatment-related serious adverse events. Treatment-emergent adverse events related to setmelanotide included mild injection site reactions and nausea with infrequent vomiting.

“The FDA’s decision to grant Priority Review to the application aligns with our belief in the potential of Imcivree to deliver clinically meaningful and statistically significant reductions in body weight and hunger for patients with BBS and Alström syndrome while also substantially improving quality of life for these patients and their families,” said Linda Shapiro, MD, PhD, Chief Medical Officer of Rhythm Pharmaceuticals. 

A Prescription Drug User Fee Act (PDUFA) target date of March 16, 2022 has been set for the application.

Setmelanotide is currently marketed under the brand name Imcivree® and is approved for chronic weight management in patients 6 years of age and older with obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance.


  1. Rhythm Pharmaceuticals announces FDA acceptance for filing and Priority Review of supplemental New Drug Application for Imcivree® (setmelanotide) for patients with Bardet-Biedl syndrome and Alström syndrome. News release. Rhythm Pharmaceuticals, Inc. Accessed November 15, 2021.
  2. Rhythm Pharmaceuticals announces positive topline results from pivotal phase 3 clinical trial evaluating setmelanotide in Bardet-Biedl and Alström syndromes. News release. Rhythm Pharmaceuticals, Inc. December 22, 2020. Accessed November 15, 2021.