Rhythm Pharmaceuticals Reports Promising Phase 2 Results for Once-Weekly RM-718 in Acquired Hypothalamic Obesity

Rhythm Pharmaceuticals has announced preliminary findings from its ongoing Phase 2 clinical trial evaluating RM-718, an investigational once-weekly MC4R agonist, in patients with acquired hypothalamic obesity (HO). The open-label study enrolled 11 participants to assess the therapy's safety and effectiveness in treating this rare neuroendocrine disorder.

Among the seven patients who completed 16 weeks of treatment, RM-718 achieved a mean body mass index (BMI) reduction of 11.6% from baseline. The company noted that these results are comparable to previously reported outcomes for bivamelagon and setmelanotide, two therapies studied for hypothalamic obesity, suggesting RM-718 may offer similar clinical benefits with a once-weekly dosing schedule.

“These encouraging results suggest that RM-718 has the potential to deliver clinically meaningful BMI reductions in patients with acquired HO,” said David Meeker, M.D., Chair, President and Chief Executive Officer of Rhythm Pharmaceuticals. “The magnitude of BMI reduction observed to date is consistent with what we have seen with both setmelanotide and bivamelagon at similar treatment durations. Importantly, we have observed very limited hyperpigmentation, with two mild cases reported isolated to the injection site. We look forward to continuing to advance RM-718 as a potential next-generation treatment option for patients living with rare MC4R pathway diseases.” 

The investigational treatment was generally well tolerated. The most frequently reported side effects included injection site reactions, nausea, and vomiting. Two mild cases of injection-site hyperpigmentation were observed without any generalized skin discoloration. As of July 16, 2026, eight patients remained on treatment, while two discontinued due to adverse events and one withdrew during the trial's extension phase.