POMC Deficiency Obesity
Pro-opiomelanocortin (POMC) deficiency obesity is a life-threatening, ultra-rare orphan disease, with approximately 50 patients reported to date. We estimate that actual prevalence of this disorder could be between 100 and 500 patients in the U.S. Patients with POMC deficiency have unrelenting hunger (hyperphagia) that begins in infancy, and they develop severe, early-onset obesity. POMC deficiency obesity results from two different homozygous genetic defects, both upstream (which refers to the relative position of the defect earlier in the pathway) of the MC4 receptor, which results in loss of function in the MC4 pathway. Currently, there is no approved treatment for the obesity and hyperphagia associated with POMC deficiency obesity.
LepR Deficiency Obesity
Leptin receptor (LepR) deficiency obesity is an ultra-rare orphan disease that results in hyperphagia and severe, early-onset obesity, with an estimated prevalence of 1% of subjects with severe, early-onset obesity. We estimate actual prevalence could be between 500 and 2,000 patients in the U.S. Like other deficiencies upstream in the MC4 pathway, LepR deficiency results in loss of function in the MC4 pathway. Therefore, patients with this indication also manifest hyperphagia and severe obesity from early childhood. Currently, there is no approved treatment for the obesity and hyperphagia associated with LepR deficiency obesity.
Bardet-Biedl syndrome is a life-threatening, ultra-rare orphan disease with a prevalence of approximately one in 100,000 in North America, which we estimate has an addressable patient population of approximately 1,500 to 2,500 patients in the U.S. Bardet-Biedl syndrome is a monogenic disorder that causes severe obesity and hyperphagia as well as vision loss, polydactyly, kidney abnormalities, among other signs and symptoms. Currently, there are no approved or effective therapies for Bardet-Biedl syndrome.
Additional Upstream Genetic Defects in the MC4 Pathway
We are also focusing on additional upstream MC4 pathway deficiencies for which setmelanotide can function as replacement therapy and provide activation of the pathway downstream of the defect, promoting satiety and weight control, including Alström syndrome, POMC heterozygous deficiency obesity, and POMC epigenetic disorders.