While pharma giants Novo Nordisk and Eli Lilly may have a solid hold on the obesity arena, Rhythm Pharmaceuticals is looking to corner a subset of the market with its Imcivree.

About 5,000 to 10,000 people in the U.S. live with acquired hypothalamic obesity, or obesity that stems from damage to the part of the brain that controls hunger and weight regulation. Drugs meant for those with general obesity have shown “limited effectiveness” in providing long-term, durable weight loss for those with the rarer condition, pediatric endocrinologist Susan Philips, M.D., explained in an April 7 press release issued by Rhythm.

Enter Imcivree (setmelanotide), a melanocortin-4 receptor (MC4R) agonist that was first approved in 2020 for patients six years and older with obesity due to rare genetic diseases proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1) or leptin receptor (LEPR).

Rhythm tested the drug in what is “believed to be” the largest and longest placebo-controlled study in those with acquired hypothalamic obesity, finding that Imcivree treatment prompted a mean BMI reduction of 16.5% from baseline, compared to a 3.3% BMI increase for those on placebo by week 52. Four out of five patients who took Imcivree cut down on their BMI by 5% or more, Rhythm said.

The “highly clinically meaningful results” from the trial could represent a “transformational milestone for Rhythm,” CEO David Meeker, M.D. said in the release. The company is now gearing up to submit a regulatory bid for a label expansion with the FDA and the European Medicines Agency in the third quarter of this year, which could “pave the way for setmelanotide to become the first-ever approved therapy for these patients.”

Rhythm plans to present full data from the trial at an upcoming medical meeting and is continuing to run the study in a supplemental cohort of 12 Japanese patients, with topline data expected in the first quarter of 2026. The results also serve to boost the company’s confidence in its next-generation MC4R agonists, which are currently being evaluated in ongoing phase 1/ 2 trials in acquired hypothalamic obesity, Meeker added.

Outside of the U.S., Rhythm estimates that there are some 5,000 to 8,000 people who have the condition in Japan and about 3,500 to 10,000 in Europe. Hypothalamic obesity typically follows brain tumors or other brain injuries and manifests in accelerated weight gain, a decline in energy expenditure and hyperphagia, a pathological condition defined by insatiable hunger and abnormal food-seeking behaviors. 

After its initial approval, Imcivree picked up another nod in 2022 for adult and pediatric patients with obesity linked to another rare genetic disease, Bardet-Biedl syndrome. Late last year, the FDA expanded the drug’s use in its current indications to children as young as two. 

In 2024, Imcivree racked up sales of $130.1 million, a boost from 2023’s $77.4 million haul. An approval for hypothalamic obesity would be the first non-genetic disease population the drug is cleared to cover, marking a significant new opportunity for the drug.