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

Key Points

• IMCIVREE’s U.S. AHO launch is showing early traction: Rhythm received more than 400 patient start forms from over 300 physicians, while its Phase III study showed an 18.8% body-weight reduction versus placebo. The company estimates the U.S. opportunity at approximately 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.

Rhythm Pharmaceuticals NASDAQ: RYTM is expanding commercialization of its rare-disease obesity treatment IMCIVREE while advancing additional melanocortin-4 receptor, or MC4R, agonists through development, Chief Financial Officer Hunter Smith said during a Canaccord Genuity fireside chat.

Smith said Boston-based Rhythm has just under 500 employees, 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. Smith said 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.

Acquired Hypothalamic Obesity Launch

Smith highlighted the U.S. launch of IMCIVREE for acquired hypothalamic obesity, or AHO, as 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, according to Smith. He said the study supported regulatory filings and was the subject of a July 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, Smith said, 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, he said. Rhythm had coverage policies in place for roughly 25% of commercial lives and 35% of Medicaid lives, and Smith said reimbursement progress was ahead of the comparable stage of the BBS launch.

“We genuinely believe this is a sustainable opportunity based on the Q2 results,” Smith said. He added that 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. Smith said the company’s confidence in the upper end of its prior 5,000-to-10,000-patient estimate increased as it identified additional tumor types and non-tumor causes that can lead to hypothalamic obesity. As of September 2025, the company had identified more than 2,000 diagnosed or suspected hypothalamic-obesity patients treated by its tier 1 and tier 2 physicians, though it has not provided an updated figure since then.

To maintain growth in BBS while its commercial team focuses on AHO, Rhythm is establishing a dedicated BBS field force of 10 territory managers. Smith said part of that team is already in place and the company expects to complete the buildout relatively soon.

International Expansion

Rhythm expects approval and reimbursement for IMCIVREE in Japan around the end of the year, which could enable a launch at that time. Smith said Japan has an elevated incidence of craniopharyngioma and that hypothalamic-obesity prevalence is estimated at 50% to 80% of U.S. prevalence despite Japan’s smaller population.

The Japanese regulator allowed Rhythm to amend its Phase III study to include a cohort of 12 Japanese patients, which Smith said was sufficient for registration. Rhythm is fully staffed in Japan, with hospital-affairs liaisons working to identify patients at major treatment centers ahead of a potential launch.

In Europe, the company has paid early-access programs in France and Italy. France granted early access based on Phase II data, while Italy’s program covers certain patients up to age 24 who developed hypothalamic obesity due to craniopharyngioma. Rhythm is also approved in Europe and, as of the day before the fireside chat, in the United Kingdom.

Germany remains a key near-term market. Smith said Rhythm has requested an exemption from Germany’s restrictions on reimbursement for lifestyle therapies, an exemption it has obtained for prior indications. The company expects a decision by year-end and hopes to launch in Germany during the first quarter if the exemption is granted.

Pipeline and Prader-Willi Syndrome

Rhythm is developing two additional clinical-stage MC4R agonists: bivamelagon, a daily oral drug, and RM-718, a weekly injectable. The company expects to begin a global Phase III study of bivamelagon in AHO before year-end, initially in patients ages 12 and older. A cohort for younger children may be added after a chewable formulation is ready.

Smith said Rhythm recently announced Phase III data for RM-718 and is evaluating whether to advance that product immediately or stage its development later.

The company is also considering a Phase III program in Prader-Willi syndrome, a genetic condition associated with severe hyperphagia and obesity. In an 18-patient single-site open-label study, with data available for 17 patients, Rhythm reported improvements after six months in body mass index, hyperphagia scores, adiposity and anxiety measures. Smith said the results were less dramatic and less uniform than those observed in AHO, reflecting the complexity of Prader-Willi syndrome.

Rhythm has not selected which of its three agents it would use in a potential Phase III Prader-Willi study, but Smith said the company expects to provide an update before year-end. The company estimates that 8,000 to 12,500 obese Prader-Willi patients are in the U.S., with diagnosis rates of approximately 85% to 90%.

Smith also said Rhythm ended the quarter with roughly $330 million in cash and believes it has sufficient cash such that additional equity should not be required, although it could pursue financing to manage balance-sheet liquidity.

About Rhythm Pharmaceuticals (NASDAQ:RYTM)

Rhythm Pharmaceuticals, Inc is a clinical‐stage biotechnology company dedicated to developing targeted therapies for rare genetic diseases of obesity and metabolic dysfunction. The company's research focuses on the melanocortin‐4 receptor (MC4R) pathway, which plays a central role in regulating appetite, energy expenditure and body weight. Using proprietary peptide technology, Rhythm aims to provide precision treatments to patients with specific genetic variants that disrupt normal weight regulation.

The company's lead investigational product, setmelanotide, is a selective MC4R agonist designed to restore signaling in patients with deficiencies in genes such as POMC, LEPR and PCSK1.

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