Rhythm's Obesity Drug Shows Promise in Rare Form of Excess Weight

Rhythm Pharmaceuticals has announced positive results from a Phase 3 clinical trial of setmelanotide, marketed as Imcivree, for the treatment of obesity caused by hypothalamic injury. The study's success could pave the way for expanded use of the drug, which is already approved for certain genetically driven forms of obesity.

Trial Results Demonstrate Significant Weight Loss

The Phase 3 trial, which enrolled 120 participants with obesity resulting from damage to the hypothalamic region of the brain, showed that patients treated with Imcivree lost an average of 16.5% of their body weight over 52 weeks. This contrasted sharply with the placebo group, which saw a 3.3% weight gain during the same period.

Notably, 80% of participants receiving Imcivree achieved a weight loss of 5% or more, meeting a key secondary endpoint of the study. These results have been described by Stifel analyst Paul Matteis as "very strong" and "above expectations."

Expanding the Market for Imcivree

Rhythm Pharmaceuticals plans to leverage these positive results to seek regulatory approval for Imcivree in treating obesity caused by hypothalamic injury. This condition can occur following tumor removal, brain injury, stroke, or inflammation from infections.

Imcivree, which earned $130 million in sales in 2024, is currently approved for use in three types of genetically driven obesity and Bardet-Biedl Syndrome, a rare metabolic disorder. The potential expansion into hypothalamic obesity represents what Matteis calls "a blockbuster opportunity with the potential for a fast ramp" in sales.

Unique Mechanism of Action in the Obesity Drug Landscape

Unlike popular GLP-1 drugs such as Wegovy and Zepbound, which modulate gut hormones, Imcivree targets the melanocortin-4 receptor (MC4R) pathway. This pathway, active in the hypothalamus, plays a crucial role in regulating hunger, caloric intake, and energy expenditure.

Imcivree's mechanism of action makes it particularly suited for treating conditions where the MC4R pathway is impaired, leading to hyperphagia – an insatiable hunger resulting in overeating.

As the obesity drug market continues to expand, with GLP-1 drugs recording billions in sales and analysts forecasting annual sales of up to $100 billion, Rhythm's focus on specialized niches could provide a competitive edge in this rapidly growing field.