A New Drug Class for the Treatment of Rare Genetic Disorders of Obesity
We are focused on developing and commercializing peptide therapeutics for the treatment of rare genetic deficiencies that result in life-threatening metabolic disorders. Our lead peptide product candidate, setmelanotide, is a potent, first-in-class melanocortin-4 receptor (MC4R) agonist for the treatment of rare genetic disorders of obesity. Setmelanotide activates MC4R, which is part of a key pathway that can regulate energy homeostasis (i.e., the body’s energy balance) and appetite. The critical role of the MC4 pathway in weight regulation was validated with the discovery that single genetic defects in this pathway result in early-onset and severe obesity.
First-generation MC4R agonists were small molecules that failed in clinical trials primarily due to safety issues—particularly increases in blood pressure—as well as limited efficacy. In contrast, setmelanotide is a peptide that retains the specificity and functionality of the naturally occurring hormone that activates MC4R.
We are focusing setmelanotide clinical development on obesity related to six single gene-related (i.e., monogenic) MC4 pathway deficiencies: Pro-opiomelanocortin (POMC) deficiency obesity, leptin receptor (LepR) deficiency obesity, Bardet-Biedl syndrome, Alström syndrome, POMC heterozygous deficiency obesity, and POMC epigenetic disorders. We believe setmelanotide has the potential to restore lost activity in the MC4 pathway by bypassing the defects upstream of MC4R and activating the MC4 pathway below such defects. In this way, setmelanotide may serve as replacement therapy to reestablish weight and appetite control in patients with these genetic disorders.
We are currently evaluating setmelanotide for the treatment of the following genetic disorders of obesity: POMC deficiency obesity, LepR deficiency obesity, Prader-Willi syndrome, Bardet-Biedl syndrome, Alström syndrome, POMC heterozygous deficiency obesity, and POMC epigenetic disorders.
Setmelanotide is currently in Phase 3 development for POMC deficiency obesity and for LepR deficiency obesity. We have demonstrated preliminary proof of concept in our Phase 2 clinical trial in Bardet-Biedl syndrome, indicating that this is also a setmelanotide-responsive, upstream MC4 pathway disorder, and this Phase 2 trial is ongoing. In addition, we have initiated Phase 2 proof-of-concept clinical trials for Alström syndrome, POMC heterozygous deficiency obesity, and POMC epigenetic disorders.
To validate the scientific and clinical importance of our Phase 2 findings, the results of this trial were published on July 21, 2016 in the The New England Journal of Medicine, and the accompanying editorial described the trial as demonstrating impressive hunger reduction and weight loss as well as improved insulin sensitivity.