Rhythm Pharmaceuticals (NASDAQ:RYTM) executives highlighted continued commercial growth for IMCIVREE and outlined a series of near-term regulatory and clinical milestones during the company’s fourth quarter and fiscal year 2025 earnings call. Management also provided updated longer-term development plans for next-generation MC4R agonists, including additional data from the Phase 2 bivamelagon program in hypothalamic obesity (HO).
IMCIVREE sales growth and inventory dynamics
Chief Financial Officer Hunter Smith said IMCIVREE net product revenue totaled $57.3 million in the fourth quarter of 2025, up 12% sequentially, and $194.8 million for the full year, an increase of approximately 50% versus 2024. Smith attributed sequential growth primarily to an increase of approximately 10% in the number of patients on reimbursed therapy globally.
Smith also discussed channel inventory effects. In the fourth quarter, vials shipped to the specialty pharmacy in the U.S. exceeded vials dispensed to patients by about 1.7 million, and inventory days on hand increased to about 20 days versus a normalized level of 10–15 days. He said this type of inventory build can represent a pull-forward of revenue and “can, with all other things being equal, have a dampening effect” on first-quarter results. On the Q&A, management also pointed to typical first-quarter payer plan renewals and patient transitions onto and off the company’s bridge program.
Commercial update: BBS and launch preparations for acquired HO
Executive Vice President and Head of North America Jennifer Lee said the company saw another “steady quarter of growth in prescriptions” in Bardet-Biedl syndrome (BBS), driven by continued efforts to educate healthcare providers and work with payers to secure reimbursement approvals. She emphasized IMCIVREE is the only approved therapy targeting the root cause of rare MC4R pathway diseases like BBS.
Looking ahead to acquired hypothalamic obesity, Lee said the company continues preparing for a potential launch pending a March 20 PDUFA goal date. She described acquired HO as a post-injury neuroendocrine disease characterized by impairment of the MC4R pathway, leading to hyperphagia and accelerated, sustained weight gain, and cited an estimated U.S. prevalence of 10,000 patients.
Lee said Rhythm expanded its sales force from 16 to 42 and has used claims data to identify providers caring for acquired HO patients. She said the company has engaged with healthcare providers who care for more than 2,000 patients diagnosed with or suspected to have acquired HO. In addition, Rhythm identified about 40 priority medical centers nationally that manage a significant concentration of acquired HO patients, with about one-third of identified patients managed within those centers. Lee also said the company expects payer policy updates following approval to occur within three to nine months.
International expansion and HO plans in Europe and Japan
Executive Vice President and Head of International Yann Mazabraud said Rhythm’s international organization grew to more than 100 employees across 13 countries during 2025. He said IMCIVREE is available in more than 25 countries outside the U.S., including eight newly added during the year, supported by ongoing BBS and POMC/LEPR access as well as reimbursed early access programs for acquired HO in France and Italy.
For Europe, Mazabraud said the company’s EMA submission for HO is under review, with an anticipated CHMP opinion in Q2 and potential EU marketing authorization in the second half of 2026. He added that French authorities renewed authorization for the reimbursed early access program, which management said reflects perceived patient benefit and unmet need.
In Japan, Mazabraud estimated acquired HO prevalence of 5,000–8,000 patients and described Japan as a “meaningful long-term opportunity.” He said the company had a positive in-person meeting with the PMDA and expects top-line data from the Phase 3 Japanese HO cohort in March. He also said that after data readout, Rhythm expects roughly 12 months of regulatory and market access work, implying a potential launch timeline “in the next 12 months from now.”
Bivamelagon HO Phase 2: 40-week data and Phase 3 requirements
CEO David Meeker highlighted an end-of-Phase 2 meeting with the FDA for the bivamelagon HO study and said the company shared nine-month data showing “persistent BMI reductions” and “consistent safety and tolerability.” He said Rhythm aims to present full 52-week data at a medical meeting mid-year.
Meeker reviewed the Phase 2 design: a 14-week randomized period across placebo and three dosing cohorts, followed by a blinded redose escalation into an open-label extension, with patients uptitrated to a target dose of 600 mg. He reiterated previously announced 14-week results in which the 400 mg and 600 mg arms achieved mean BMI reductions of 7.7% and 9.3%, respectively.
At the time of the update, Meeker said 26 of 28 patients remained active in the trial (including retained dropouts), and 25 of 28 remained on active drug. He noted one discontinuation after the first visit due to rectal bleeding judged unrelated to study drug, and one patient in the 600 mg cohort who chose not to continue into the open-label period for personal reasons.
At 40 weeks, Meeker said the mean BMI decrease was 10.8% for the original 400 mg cohort (including a non-compliant patient) and 14.3% for the original 600 mg cohort (including a non-compliant patient who gained weight and a patient who dropped at 14 weeks). He also compared those figures to a 15% 40-week result from the setmelanotide Phase 3 HO data in patients not on a concomitant GLP-1, as discussed on the call.
On tolerability, Meeker said bivamelagon is better tolerated when taken with a small amount of food, and the side effect profile “continues to mimic” setmelanotide, with nausea and vomiting tending to occur early and then improving, and diarrhea described as sporadic and mild, with no discontinuations due to diarrhea. He said compliance issues in the trial were predominantly in younger teenagers due to pill size, and the company plans easier-to-swallow single-pill formulations (200 mg, 400 mg, and 600 mg) and a chewable tablet for younger patients.
Regarding Phase 3, Meeker characterized the FDA meeting as “highly constructive” and said the agency confirmed bivamelagon is ready to move to Phase 3. However, he said the FDA was firm that, as a new chemical entity, the program would require a full 12-month double-blind randomized controlled trial and a larger patient number to build the safety database—closer to the 142-patient setmelanotide trial—rather than a shorter six-month blinded period. Meeker said Rhythm expects to initiate the Phase 3 HO study by year-end 2026 and plans to run it largely in countries where setmelanotide will not be available for acquired HO in the near future to facilitate enrollment.
Pipeline milestones: HO PDUFA, Japan cohort, EMANATE, PWS, and RM-718
Meeker listed multiple upcoming milestones, including the HO PDUFA, top-line data from the Japanese HO cohort, and the EMANATE readout, all expected in March. For EMANATE, he said the company is working to release top-line data by the end of March. He also said the Prader-Willi syndrome (PWS) trial remains on track for a six-month data update by mid-year, with 17 of 18 patients remaining on treatment and no additional data cut available for this call.
Management also said RM-718, a weekly formulation, continues enrolling in HO, with initial three-month data expected by mid-year.
In guidance, Smith said Rhythm expects 2026 non-GAAP operating expenses of $385 million to $415 million, including non-GAAP R&D of $197 million to $213 million and non-GAAP SG&A of $188 million to $202 million. He attributed the increase to investments in next-generation MC4R agonist development and manufacturing, U.S. commercial support for the HO launch, and building operations in Japan. Rhythm ended 2025 with about $389 million in cash, cash equivalents, and short-term investments, which Smith said should fund planned operations for at least 24 months.
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.
