BOSTON, August 4, 2026
Rhythm Pharmaceuticals announced encouraging preliminary Phase 2 clinical trial results for RM-718, its investigational once-weekly MC4R agonist, in patients with acquired hypothalamic obesity (HO). The study demonstrated a mean 11.6% reduction in body mass index (BMI) from baseline after 16 weeks among evaluable patients, highlighting the therapy’s potential as a next-generation treatment for rare neuroendocrine disorders. The company noted that the magnitude of BMI reduction was consistent with previously observed outcomes for both setmelanotide and bivamelagon, supporting continued development of RM-718. Importantly, the investigational therapy exhibited a favorable preliminary safety profile, with only two mild cases of injection-site hyperpigmentation and no generalized skin pigmentation observed. These findings reinforce Rhythm’s strategy of developing MC1R-sparing MC4R agonists designed to minimize pigmentation-related side effects while delivering meaningful weight-loss benefits.
Phase 2 Trial Demonstrates Strong Early Efficacy and Favorable Safety
The ongoing open-label Phase 2 study enrolled 11 patients diagnosed with acquired hypothalamic obesity, a rare disorder caused by damage to the hypothalamus that results in uncontrolled hunger and severe weight gain. Of the participants, seven patients completed 16 weeks of treatment, achieving a mean BMI reduction of 11.6%. According to the company, these efficacy results compare favorably with historical data from bivamelagon, which demonstrated a 10.1% BMI reduction at 14 weeks, and setmelanotide, which achieved a 10.1% reduction after 16 weeks across Phase 2 and Phase 3 studies. RM-718 was generally well tolerated, with the most common adverse events including injection-site reactions, nausea, and vomiting. Two participants discontinued treatment because of adverse events, while one patient withdrew during the extension phase. As of mid-July 2026, eight participants remained on active treatment, including two who had not yet completed the 16-week evaluation period, allowing the study to continue generating additional clinical evidence.
Next-Generation MC4R Agonist Designed to Improve Patient Experience
RM-718 has been engineered as a highly selective MC4R agonist that avoids significant activation of the MC1R receptor, a mechanism believed to reduce the frequency and severity of hyperpigmentation, one of the known challenges associated with existing therapies targeting the melanocortin pathway. The preliminary Phase 2 data support this design strategy, as only localized mild injection-site pigmentation was reported. Rhythm Pharmaceuticals believes that RM-718 could become an important addition to its expanding portfolio of therapies for rare MC4R pathway diseases, complementing its marketed product IMCIVREE® (setmelanotide) and other investigational candidates such as bivamelagon. Beyond improving weight management, the company aims to deliver therapies that address the underlying biological mechanisms responsible for hyperphagia and severe obesity in rare neuroendocrine disorders while improving long-term tolerability and patient adherence.
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Rhythm Expands Pipeline for Rare Neuroendocrine Disorders
The encouraging preliminary findings strengthen Rhythm Pharmaceuticals’ leadership in developing therapies targeting the melanocortin-4 receptor pathway. The company continues advancing multiple clinical-stage and preclinical programs focused on rare obesity disorders and congenital endocrine diseases. With RM-718 demonstrating clinically meaningful BMI reductions alongside a favorable early safety profile, Rhythm expects the program to contribute to its long-term strategy of delivering differentiated treatments for patients with limited therapeutic options. Additional follow-up data from the ongoing study are expected to further define the drug’s efficacy and safety profile, while the company continues to expand its research efforts across rare neuroendocrine diseases where targeted MC4R activation may provide significant clinical benefit.
Source:Rhythm Pharmaceuticals press release
