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MC4R agonist promising for treatment of rare form of obesity
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Two patients with a rare congenital proopiomelanocortin deficiency, which leads to increased hunger, experienced weight loss while treated with the melanocortin-4 receptor agonist setmelanotide, according to results from a phase 2 study of the drug.
“POMC is a gene that is cleaved into a hormone called [melanocyte-stimulating hormone] (MSH),” Peter Khnen, MD, a pediatrician with the Institute for Experimental Pediatric Endocrinology at Charité–Universitätsmedizin Berlin, told Endocrine Today. “This peptide is able to activate the satiety center within the brain. If there is a lack of MSH, as in patients with a mutation in the POMC gene, this leads to persistent hunger and, based on this hyperphagia, to severe early onset obesity. By restoring this lost function of MSH it is possible to activate the satiety center, which in turn leads to a reduction of hyperphagia and weight loss. This study was focused on patients with the very rare disease of a POMC deficiency. In this patient cohort we have evidence that setmelanotide has a transformational impact on hyperphagia and body weight.”
Khnen and colleagues studied two patients with POMC deficiency who were treated with setmelanotide (Rhythm Pharmaceuticals). Both patients had sustained reduction in hunger and weight loss. Patient 1 (baseline weight, 155 kg) lost 51 kg after 42 weeks, and Patient 2 (baseline weight, 152.8 kg) lost 20.5 kg after 12 weeks.
“The efficacy of setmelanotide to reduce body weight in the two patients suggests that this melanocortin-4 receptor agonist might be effective in the treatment of other monogenic defects of the hypothalamic leptin-melanocortin pathway, such as leptin-receptor deficiency and PCSK1 deficiency, for which no effective pharmacologic therapy is available,” researchers wrote. – by Cassie Homer
Disclosure: Khnen reports no relevant financial disclosures. Please see the full study for all other authors’ relevant financial disclosures.
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