Promising Data For Setmelanotide For Genetic Obesity

rhythm logoOne of the most common genetics variations related to obesity found in the general population involves the melanocortin-4  (MC4) receptor, which plays  a key role in appetite regulation.

Now Rhythm Pharmaceuticals released its first data on the use of their novel MC4-R agonist setmelanotide in patients with obesity and proven MC4-R defects.

According to their press release,

“In this pilot study, obese (BMI >/= 30kg/m2) patients with a heterozygous MC4R loss-of-function mutation were enrolled in a double-blind, placebo-controlled, randomized, parallel-group study for 4 weeks.  Eight patients (six active, two placebo) received placebo or RM-493 at 0.01 mg/kg/day (~ 1 mg/day) by continuous subcutaneous infusion. Key endpoints were safety, weight loss, waist circumference, and caloric intake. Setmelanotide was well tolerated over 4 weeks, with no serious adverse events or discontinuations. The most common side effects were headache and skin tanning, with the latter believed to be due to off-target activity at the related melanocortin-1 receptor. Setmelanotide demonstrated strong trends for placebo-subtracted weight loss (2.62 kg; p=0.088); WC (5.1 cm; p=0.188) and daily caloric intake (351 kCal/day; p=not significant), without clinically important effects on heart rate or blood pressure.”

Overall, the company has taken (the perhaps wise) option of focussing their development program on genetic forms of obesity.

Currently they have an ongoing Phase 2 setmelanotide trial for the treatment of Prader-Willi syndrome and a second Phase 2 trial for the treatment of pro-opiomelanocortin (POMC) deficiency obesity, a very rare, life-threatening genetic disorder of the MC4 pathway associated with unrelenting appetite and obesity.

Clearly, this will be a space to watch.

Edmonton, AB