Rhythm Pharmaceuticals’ Imcivree reduced fat—while boosting muscle—in patients with Prader-Willi syndrome.
Rhythm Pharmaceuticals’ weight loss injection Imcivree lowered body mass index in a Phase 2 study of Prader-Willi syndrome, helping the drug bounce back from a recent late-stage disappointment.
Already approved for a handful of conditions associated with obesity, Imcivree (setmelanotide) is Rhythm’s only marketed drug, bringing in $194.8 million in 2025. Aside from Prader-Willi syndrome, the biotech is also advancing Imcivree for a host of other rare and genetic obesities.
At the six-month analysis, patients on Imcivree saw a 3.06% mean decrease in body mass index (BMI). This includes a 3.11% average reduction for adult patients and a 3% drop in children, according to data shared Saturday and slated for presentation at the 2026 annual meeting of the Endocrine Society.
Body scans additionally showed that Imcivree’s effects were driven largely by a reduction in fat rather than muscle. Fat mass dropped by 4.19% in 16 patients treated with Imcivree, while lean mass increased by 0.74%, according to Rhythm’s release. Five of the seven pediatric patients saw at least a 2.95% increase in lean mass.
These outcomes “look better than expected,” analysts at Stifel told investors in a note on Sunday, calling the data “encouraging.” In particular, the firm said that Imcivree showed an “improved weight loss vs the prior cut,” pointing to a December 2025 readout showing weight changes ranging from a 4.8% reduction to a 2.4% increase.
“The mean BMI reductions was roughly ~1.8% at the time,” Stifel said Sunday. “The data have improved and reflect positive signal for setmelanotide.”
The analysts also noted Rhythm’s data on hyperphagia, or extreme hunger. Using the Hyperphagia Questionnaire for Clinical Trials score—a validated tool to measure hyperphagia outcomes and symptoms in patients with Prader-Willi syndrome—the biotech documented “clinically meaningful” improvements after treatment with Imcivree.
“The hyperphagia signal here looks encouraging,” Stifel said, noting however that the questionnaire used in the study “is a more subjective endpoint” than BMI. Still, the firm noted that “there may be multiple paths to market here, including a faster path on a hyperphagia driven trial that maybe isn’t 100% derisked but certainly looks like it has a realistic probability-of-success.”
Imcivree is an MC4 receptor agonist that works by regulating hunger and energy expenditure, while also promoting feelings of satiety. The drug was first approved in November 2020 for chronic weight management in patients with obesity linked to deficiency of the POMC, PCSK1 or LEPR proteins.
Imcivree won a label expansion in 2022, allowing its use in Bardet-Biedl Syndrome, a rare genetic disorder that causes obesity in children.
In March, however, the drug failed a Phase 3 basket study that looked at its weight loss efficacy in a clutch of rare obesities linked to mutations in four genes related to the melanocortin-4 receptor pathway: POMC/PCSK1, LEPR, SRC1 (NCOA1) or SH2B1. Across four substudies focused on each of these variants, Imcivree failed to significantly outperform placebo at lowering body weight.
Days later, the drug won the FDA’s go-ahead for hypothalamic obesity.
