Rhythm Pharmaceuticals, Inc. (NASDAQ: RYTM) has announced positive topline results from its phase 2 trial of bivamelagon, an oral melanocortin-4 receptor (MC4R) agonist, in patients with acquired hypothalamic obesity. The trial demonstrated statistically significant and clinically meaningful reductions in body mass index (BMI) at 14 weeks of treatment.
In the 14-week, double-blind, four-arm, placebo-controlled portion of the trial, bivamelagon achieved the following BMI reductions from baseline: -9.3% in the 600mg cohort (p-value=0.0004) -7.7% in the 400mg cohort (p-value=0.0002) -2.7% in the 200mg cohort (p-value=0.0180) Patients in the placebo cohort experienced a 2.2% increase in BMI over the 14 weeks.
Comparing the results to prior setmelanotide trials, bivamelagon demonstrated BMI reductions consistent with those achieved with setmelanotide therapy in similar patient populations. The mean BMI reductions achieved by patients on bivamelagon were -8.8% and -10.1% in the 400mg and 600mg cohorts, respectively, at 14 weeks, compared to -9.7% and -10.5% in a pooled patient population from phase 2 and phase 3 trials of setmelanotide therapy at 12 weeks and 16 weeks, respectively.
Patients reported meaningful reductions in their ‘most’ hunger scores at 14 weeks on therapy compared to placebo, with those in the 600mg and 400mg cohorts achieving a mean reduction greater than 2.8 points in their ‘most’ hunger scores measured on a 10-point scale.
The safety and tolerability results of bivamelagon were consistent with MC4R agonism and mechanism of action, with the most common reported adverse events being mild episodes of diarrhea and nausea. Limited instances of localized hyperpigmentation were observed, and only one patient discontinued therapy due to a serious adverse event (rectal bleeding).
Following these positive results, Rhythm Pharmaceuticals plans to request an end-of-phase 2 meeting with the U.S. Food and Drug Administration (FDA) and seek scientific advice from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) to advance bivamelagon in acquired hypothalamic obesity.
Acquired hypothalamic obesity is a rare form of obesity that occurs following damage to the hypothalamic region of the brain, and Rhythm estimates there are 5,000 to 10,000 people living with this condition in the U.S., 5,000 to 8,000 people in Japan, and 3,500 to 10,000 people in the E.U.
Rhythm Pharmaceuticals is a commercial-stage biopharmaceutical company focused on transforming the lives of patients and their families living with rare neuroendocrine diseases. The company's lead asset, Imcivree® (setmelanotide), is an MC4R agonist approved by the U.S. FDA to treat hyperphagia and severe obesity in specific patient populations.
Rhythm Pharmaceuticals will be presenting results from the bivamelagon trial at the Endocrine Society’s annual meeting (ENDO 2025) on July 12, 2025, in San Francisco.
The full press release is available on Rhythm Pharmaceuticals' website. Following these announcements, the company's shares moved -0.3%, and are now trading at a price of $88.73. For the full picture, make sure to review RHYTHM PHARMACEUTICALS, INC.'s 8-K report.
