Longer-term results back Rhythm’s ultrarare obesity drug

Rhythm Pharma has additional data for its first-in-class obesity therapy setmelanotide—published in the prestigious journal Nature Medicine—showing that the drug’s effects can extend for over a year.

The new data comes just a few months after the Boston-based biotech’s oversubscribed IPO driven by enthusiasm for setmelanotide, which works as a melanocortin-4 receptor (MCR4) agonist and is being developed for ultrarare genetic diseases that cause obesity.

The new phase 2 data are from three patients with leptin receptor deficiency (LepR) obesity, which affects around 2,000 people in the U.S. and along with severe weight gain is associated with an uncontrollable desire to eat (hyperphagia). According to the authors, the results match earlier clinical experience with setmelanotide in pro-opiomelanocortin (POMC) deficiency obesity.

Setmelanotide given as a daily subcutaneous injection achieved significant reductions in hunger feelings as well as weight for two young adult male patients, one of whom lost more than 21% body weight over the first 26 weeks of treatment, which was sustained for another 35 weeks.

He also saw a reduction from 9 to 1 or 2 on a 10-point hunger scale—with zero being no hunger and 10 being ravenously hungry. The second man also experienced significant weight loss and also saw his hunger score slashed from 9.5 to 2.

A third patient, an adolescent female who was sister to one of the other subjects, initially did well on weight and hunger scores but midstudy started to take the drug at the wrong time and dose, resulting in weight gain presumably because the drug’s effects were occurring at night. She’s back on the correct regimen now and data is being collected, according to the authors of the study.

Setmelanotide was also well-tolerated, a crucial finding as earlier-generation MCR4 agonists such as Eli Lilly’s LY2112688 had significant side effects including elevations in blood pressure and heart rate.

Rhythm says its precise mechanism of action differentiates it from these earlier candidates. Also, lab data from the new study suggests that it could have activity in other forms of obesity, specifically those caused by mutations in the MCR4 receptor that the natural ligand (melanocyte stimulating hormone or MSH) doesn’t seem to affect.

The new data are "an important milestone for our clinical development program and for people living with rare genetic disorders of obesity who currently do not have approved treatment options," according to Rhythm’s CEO Keith Gottesdiener, M.D., who notes that the drug is in a phase 3 trial in LepR obesity that should complete enrollment later this year.

The company—a 2016 Fierce15 winner—is also expecting its phase 3 trial in POMC obesity to read out in the first half of next year, setting up a possible marketing application afterwards.

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