Rhythm Pharmaceuticals announced positive topline results from two pivotal phase 3 studies evaluating setmelanotide for the treatment of pro-opiomelanocortin (POMC) and leptin receptor (LEPR) deficiency obesities.
Setmelanotide, a melanocortin-4 receptor (MC4R) agonist, works by activating the MC4R to regulate energy expenditure and appetite. The MC4R pathway consists of variants in genes (eg, POMC and LEPR genes) associated with early-onset obesity.
Both phase 3 trials were multicenter, open-label, single-arm studies that evaluated the efficacy and safety of setmelanotide in patients aged ≥6 years with either POMC or LEPR deficiency obesity for approximately 1 year. The study design included 12 weeks of therapeutic dose, followed by an 8-week blinded, drug withdrawal phase and lastly, 32 weeks of therapeutic dose to complete 1 year of treatment. The primary end point for both studies assessed the percentage of patients with ≥10% weight loss; key secondary end points included the mean percent reduction from baseline of body weight and most hunger rating, and hunger score responder analysis comparing the proportion of patients with ≥25% reduction in hunger score.
Results from the POMC deficiency study showed 8 out of 10 patients met the primary end point of ≥10% weight loss (P <.0001); the mean reduction from baseline in body weight was -25.4% (90% CI: -28.80, -21.98; P <.0001), and the mean reduction in most hunger rating was -27.8% (90% CI: -40.58, -14.96; P =.0005). Additionally, 50% of the patients met or exceeded a 25% improvement in hunger scores (P =.0004). Overall, the mean weight loss for these patients was 70.2lbs, over 1 year.
Results from the LEPR deficiency study showed 5 out of 11 patients met the primary end point of ≥10% weight loss (P =.0001); the mean reduction from baseline in body weight was -12.5% (90% CI: -16.10, -8.83; P <.0001), and the mean reduction in most hunger rating was -41.9% (90% CI: -54.76, -29.09; P <.0001). Additionally, 72.7% of the patients met or exceeded a 25% improvement in hunger scores (P <.0001). Overall, the mean weight loss for these patients was 36.8lbs, over 1 year.
The Company noted that during the 8-week drug withdrawal phase, patients in both trials gained weight and experienced an increase in hunger with an approximate mean weight increase of >11lbs. Full detailed data from both studies will be presented at an upcoming medical meeting.
“We believe these statistically significant data demonstrate setmelanotide’s ability to induce marked weight loss and substantially reduce hunger and we are excited about the potential difference we can make in the lives of people with rare genetic disorders of obesity,” said Keith Gottesdiener, MD, CEO of Rhythm. “We believe these pivotal data are the first step towards making a positive impact for people affected by rare genetic disorders of obesity who have grown up with insatiable hunger and early-onset, rapid weight gain that often leads to debilitating comorbidities.”
Regarding safety, treatment-emergent adverse events included injection site reactions, nausea, vomiting, and increased hyperpigmentation.
The FDA has previously granted Breakthrough Therapy designation to setmelanotide.
For more information visit ir.rhythmtx.com.