Rhythm Pharmaceuticals announced that its exploratory Phase 2 study of setmelanotide in patients with Prader‑Willi syndrome (PWS) produced encouraging preliminary results, with measurable reductions in body mass index (BMI) and hyperphagia at both three‑ and six‑month time points. The study enrolled 18 participants aged 6‑65 years who had a BMI of at least 30 kg/m² (or the 95th percentile for those under 18). At month 3, 6 of 8 evaluable patients achieved a BMI reduction, and at month 6, 3 of 5 patients maintained a BMI decline, while 6 of 7 patients showed meaningful decreases in the Hyperphagia Questionnaire for Clinical Trials (HQ‑CT) score. Seventeen of the 18 participants remained on therapy through the data cut‑off of November 14, 2025.
The company’s CEO, David Meeker, said the data give Rhythm confidence to advance setmelanotide into a Phase 3 registrational trial for PWS, pending successful completion of the current study. Meeker highlighted that the trial’s positive signals address a critical unmet need in a rare genetic disorder characterized by relentless hunger and severe obesity, and that a new indication would broaden the drug’s addressable market beyond its existing approvals for Bardet‑Biedl syndrome, POMC, PCSK1, and LEPR deficiencies. Principal investigator Jennifer Miller noted that the interim data “offer meaningful insight into the potential for a future treatment option that could help address the unique and critical needs of patients living with PWS.”
In addition to the PWS study, Rhythm announced the launch of a Part D arm in its Phase 1 program for the weekly MC4R agonist RM‑718. The new arm will enroll up to 20 PWS patients and is expected to begin screening in December 2025, further diversifying the company’s pipeline in rare neuroendocrine obesity disorders. The RM‑718 program underscores Rhythm’s strategy to expand its MC4R platform across multiple indications while leveraging its expertise in rare disease therapeutics.
Market reaction to the announcement was robust, with analysts noting that the positive Phase 2 data could accelerate the company’s path to a new indication and unlock a sizable revenue stream. The news was cited as a key driver behind the recent surge in investor interest, reflecting confidence in Rhythm’s ability to translate early clinical signals into a registrational program. Analysts also emphasized the company’s strong track record of bringing MC4R agonists to market, which bolsters expectations for the PWS indication.
Looking ahead, Rhythm’s next milestones include the completion of the Phase 2 study, the initiation of the Phase 3 trial, and the ongoing development of RM‑718. The company’s focus on rare obesity disorders positions it to capture a niche but high‑impact market, while the expansion of its MC4R platform may provide additional growth opportunities in the broader obesity and metabolic disease space. The preliminary data reinforce Rhythm’s strategic narrative of leveraging a proven mechanism of action to address unmet medical needs in rare diseases, potentially reshaping its long‑term revenue trajectory.
The content on BeyondSPX is for informational purposes only and should not be construed as financial or investment advice. We are not financial advisors. Consult with a qualified professional before making any investment decisions. Any actions you take based on information from this site are solely at your own risk.