Rhythm Pharmaceuticals And Setmelanotide In Rare Obesity

Summary

• Liver Therapy Forum weekly digest provides an overview of what's happening in therapeutics for obesity in 2019. The focus this week is Rhythm Pharmaceuticals.
• Rare genetic obesity differs from normal obesity in that these individuals have an “insatiable abnormal hunger” and document weight increase even with a restricted diet and exercise regimen.
• Setmelanotide, a melanocortin-4 receptor agonist, represents a novel drug candidate that affects appetite regulation to impact breakthrough weight loss (>10%) in genetically obese individuals.

Market Assessment

Rhythm Pharmaceuticals (NASDAQ:RYTM) is a small-cap ($695M) biopharma developing anti-obesity therapeutics for rare and ultra-rare genetic obesity disorders. The lead drug candidate, setmelanotide (formerly RM-493), is a melanocortin-4 receptor (MC4R) agonist peptide in clinical trials for rare genetic obesity disorders associated with pro-opiomelanocortin (POMC), leptin receptor (LEPR) deficiency as well as Bardet-Biedl syndrome (BBS) and Alström syndrome. The global prevalence of rare genetic obesity is not fully known, but misdiagnosis and/or underdiagnosis could be contributing factors.

In Q3/2019, Rhythm reported that setmelanotide was clinically successful in a Phase 3 study in patients diagnosed with POMC and LEPR deficiency-mediated obesity disorders. Setmelanotide binds to and activates the MC4R. In POMC, the Q3/2019 top-line data from the pivotal Phase 3 study confirmed the clinically meaningful benefits of setmelanotide in POMC-deficient individuals:

Eight of 10 patients with POMC deficiency obesity achieved the primary endpoint of greater than 10 percent weight loss over approximately one year (p<0.0001). The mean reduction from baseline in body weight for POMC deficiency obesity patients was -25.4 percent (p<0.0001), and the mean reduction from baseline in most hunger rating for POMC deficiency obesity patients was -27.8 percent (p=0.0005). In addition, 50 percent of the POMC deficiency obesity patients in the trial met or exceeded a 25 percent improvement in self-reported hunger scores (p=0.0004). Mean weight loss for these patients was 31.9 kg, or 70.2 pounds, over one year on therapy.

Data from the pivotal Phase 3 study in LEPR-deficient individuals confirmed the therapeutic promise of setmelanotide:

Five of 11 patients with LEPR deficiency obesity achieved the primary endpoint of greater than 10 percent weight loss over one year (p=0.0001). The mean reduction from baseline in body weight for LEPR deficiency obesity patients was -12.5 percent (p<0.0001), and the mean reduction from baseline in most hunger rating for LEPR deficiency obesity patients was -41.9

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