Rhythm Presents Cardiovascular Safety Data from Phase 1b/2a Clinical Trials of Setmelanotide in Obesity

Nov 06, 2015, 08:42 ET from Rhythm

BOSTON, Nov. 6, 2015 /PRNewswire/ -- Rhythm Pharmaceuticals, Inc. announced today the presentation of results from an evaluation of cardiovascular safety in three Phase 1b/2a clinical trials of setmelanotide (RM-493), the company's novel melanocortin-4 receptor (MC4R) agonist, in obese patients. Analysis of the data indicates that setmelanotide treatment resulted in little, if any, evidence of blood pressure or heart rate change from baseline versus placebo at doses that resulted in weight loss in short-term trials. The study results were disclosed in a poster presentation at the ObesityWeek 2015 conference in Los Angeles.

In the poster presentation at ObesityWeek 2015 entitled, "Analysis of the Synthetic Peptide RM-493, a Melanocortin-4 Receptor (MC4R) Agonist, on Cardiovascular Parameters in Three Phase1b/2a Studies," Rhythm presented data assessing blood pressure and heart rate from one single-dose Phase 1, randomized, placebo-controlled crossover study; and three Phase 1b/Phase 2a randomized, double-blind, placebo-controlled, parallel-group, multiple-dose studies, all designed to evaluate the safety, tolerability, and efficacy of subcutaneously administered setmelanotide in a total of 159 obese (92 treated with setmelanotide and 62 with placebo) but otherwise healthy patients with a body mass index (BMI) of >/= 30 kg/m2. Rhythm monitored blood pressure and heart rate primarily by 24-hour ambulatory blood pressure at baseline and at one to two weeks postdose. In addition, pharmacokinetic (PK) and pharmacodynamic (PD) analyses on blood pressure and heart rate were conducted. 

Clinical highlights from the study include:

  • There was little, if any, evidence of blood pressure or heart rate change from baseline versus placebo across setmelanotide clinical studies
  • There was no evidence of a PK/PD relationship for blood pressure or heart rate

"From the outset of the setmelanotide development program, we have focused carefully on assessing any potential effects on cardiovascular function," said Keith Gottesdiener, CEO of Rhythm. "We have seen little, if any, evidence of blood pressure or heart rate changes compared with placebo in clinical trials to date, preliminarily supporting an important differentiation of setmelanotide from first-generation MC4 agonists. We are greatly encouraged by these assessments, and we will continue to carefully monitor the safety of setmelanotide in ongoing and future clinical trials."

About Setmelanotide (RM-493)
Setmelanotide is a potent, first-in-class MC4R agonist in development for the treatment of obesity caused by genetic deficiencies in the MC4 pathway, a key pathway in humans that regulates energy expenditure, homeostasis, and appetite. The critical role of the MC4 pathway in weight regulation was validated with the discovery that single genetic defects along this pathway result in early onset and severe obesity. A Phase 2 setmelanotide trial is ongoing for the treatment of Prader-Willi syndrome (PWS), a rare genetic disorder that causes life-threatening obesity. Recent scientific evidence implicates defects in the MC4 pathway as the likely cause of the weight and appetite abnormalities in PWS. A second Phase 2 trial is ongoing 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.

About Rhythm (www.rhythmtx.com)
Rhythm is a biopharmaceutical company focused on developing peptide therapeutics for the treatment of rare genetic deficiencies that result in life‑threatening metabolic disorders. Rhythm's lead peptide product candidate is setmelanotide, a first‑in‑class melanocortin‑4 receptor, or MC4R, agonist for the treatment of rare genetic disorders of obesity. The company is based in Boston, Massachusetts.