Weight reduction in patients with hypothalamic obesity treated with setmelanotide for 12 months

Roth Christian L.; Ashley Shoemaker; Michael Gottschalk; Jennifer Miller; Guojun Yuan; Sonali Malhotra; Cecilia Scimia; Abuzzahab M. Jennifer

doi:10.1530/endoabs.99.EP56

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Endocrine Abstracts (2024) 99 EP56 | DOI: 10.1530/endoabs.99.EP56

ECE2024 Eposter Presentations Diabetes, Obesity, Metabolism and Nutrition (383 abstracts)

Weight reduction in patients with hypothalamic obesity treated with setmelanotide for 12 months

Christian L. Roth ¹ , Ashley Shoemaker ² , Michael Gottschalk ³ , Jennifer Miller ⁴ , Guojun Yuan ⁵ , Sonali Malhotra ⁶ , Cecilia Scimia ⁵ & M. Jennifer Abuzzahab ⁷

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¹Seattle Children’s Research Institute; Division of Endocrinology, Department of Pediatrics, University of Washington, Seattle, Seattle, United States; ²Ian Burr Division of Endocrinology and Diabetes, Vanderbilt University Medical Center, Nashville, United States; ³Pediatric Endocrinology, University of California San Diego/Rady Children’s Hospital, San Diego, United States; ⁴Pediatric Endocrinology, Department of Pediatrics, College of Medicine, University of Florida, Gainesville, United States; ⁵Rhythm Pharmaceuticals, Inc., Boston, United States; ⁶Rhythm Pharmaceuticals, Inc.; Harvard Medical School; Massachussetts General Hospital, Boston, United States; ⁷Pediatric Endocrinology and Diabetes, Children’s Minnesota, Saint Paul, United States

Background: Hypothalamic obesity (HO) is an acquired form of severe obesity characterized by rapid and excessive weight gain resulting from insult to the hypothalamus—primarily caused by tumor invasion, resection, or radiotherapy—that can impair melanocortin-4 receptor (MC4R) pathway signaling. Treatment with setmelanotide, an MC4R agonist, resulted in weight and hunger reduction at 16 weeks in a Phase 2 trial of patients with HO. Here, we report changes in weight-related parameters after 12 months of setmelanotide treatment in patients with HO who entered a long-term extension (LTE) trial.

Methods: The Phase 2, multicenter, open-label study (NCT04725240) was a 16-week trial in patients aged ≥6 to ≤40 years with a clinical diagnosis of HO. Patients who demonstrated adequate safety and meaningful clinical benefit were eligible to enroll in the LTE trial (NCT03651765). Mean (standard deviation [SD]) percent change in body mass index (BMI) for all patients and mean (SD) change in percent of the 95th BMI percentile (%BMI₉₅) for children (aged <18 years) from index trial baseline to Month 12 of setmelanotide treatment were assessed.

Results: Of 14 patients who entered the LTE, 12 (86%) received ≥12 months of setmelanotide at the time of analysis. One adult who experienced nausea discontinued study drug at 7 months and 1 child who had been lost to follow-up reconsented and reentered the LTE but did not have 12-month data. At Month 12, the mean (SD) percent BMI change from baseline was −24.9% (13.0%) across all patients (n=12) and in children (n=11), the mean (SD) change in %BMI₉₅ was −39.5 (19.4) percentage points. No new safety signals were identified.

Conclusions: In a heterogeneous population of patients with HO secondary to treatment of hypothalamic tumors, 12 months of setmelanotide treatment was associated with sustained meaningful BMI improvement with no new safety signals.