Rhythm Pharmaceuticals Eyes AHO Growth, Global IMCIVREE Expansion and Pipeline Catalysts

Rhythm Pharmaceuticals is expanding commercialization of its rare-disease obesity treatment IMCIVREE while advancing additional melanocortin-4 receptor, or MC4R, agonists through development. The company has operations in more than a dozen countries and market access in approximately 24 countries. Its primary therapy, setmelanotide, marketed as IMCIVREE, is an MC4R agonist approved for rare forms of obesity associated with disruptions in the hypothalamic pathway that regulates hunger. IMCIVREE was initially developed for ultra-rare genetic obesity conditions including POMC and leptin receptor deficiencies. Rhythm later received approval in 2022 for Bardet-Biedl syndrome, or BBS, following a global Phase III study. The company had been operating at a quarterly revenue run rate of about $60 million during a period driven primarily by BBS and certain POMC/LEPR revenue.

The U.S. launch of IMCIVREE for acquired hypothalamic obesity, or AHO, is a major development for the company. AHO can result from hypothalamic damage caused by tumors, including craniopharyngioma, or from injury, radiation or trauma. Rhythm’s Phase III study in AHO enrolled 130 patients globally and showed that patients receiving setmelanotide lost 18.8% of body weight compared with placebo. The study supported regulatory filings and was the subject of an article in the New England Journal of Medicine, along with an editorial discussing the MC4R pathway’s role in obesity treatment.

During the first full quarter following the U.S. AHO launch, Rhythm received more than 400 patient start forms over 14 weeks, including the period between approval and the beginning of the quarter. Those forms were written by more than 300 physicians, indicating broad prescriber participation rather than concentrated prescribing activity. Approximately two-thirds of prescriptions approved as of the quarter-end had been approved through prior authorization. Rhythm had coverage policies in place for roughly 25% of commercial lives and 35% of Medicaid lives, and reimbursement progress was ahead of the comparable stage of the BBS launch. Incoming start-form activity had not slowed after the quarter ended and that the company had not yet reached or activated all targeted specialty centers and community physicians. Rhythm estimates the U.S. AHO opportunity at about 10,000 patients.

Rhythm is pursuing international expansion, with potential Japanese approval and reimbursement by year-end and a possible Germany launch in the first quarter if a reimbursement exemption is granted. The pipeline includes daily oral bivamelagon and weekly injectable RM-718, with a global Phase III AHO study for bivamelagon expected before year-end. Rhythm is also evaluating a Phase III program in Prader-Willi syndrome and ended the quarter with roughly $330 million in cash.