Significant weight loss among patients with hypothalamic obesity seen with setmelanotide
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SAN DIEGO — Treatment with the melanocortin-4 receptor agonist setmelanotide was associated with significant weight loss among patients with hypothalamic obesity, according to a presenter at ObesityWeek.
“Patients with hypothalamic obesity suffer a lot because it's an extreme obesity and it is very difficult to treat. It's much more difficult to treat compared to common obesity. Therefore, to find something to treat those complicated forms of obesity is very impactful for these patients,” Christian L. Roth, MD, professor in the division of endocrinology in the department of pediatrics at the University of Washington and Seattle Children’s Research Institute, told Healio. “I'm very glad to see that it seems that we have one potential drug for treating obesity related to hypothalamic damage, which typically occurs in response to a tumor that is located in the hypothalamus and its treatment by surgery and/or radiation.”
Researchers enrolled 18 patients (mean age, 15 years; 61.1% male) with hypothalamic obesity aged 6 to 40 years across five U.S. sites as of August 2022. Study participants had varied tumor presentation. All patients underwent open-label dose titration with a final dose of setmelanotide 3 mg (Rhythm Pharmaceuticals) delivered subcutaneously once daily. Patients who were aged 6 to 15 years received setmelanotide 1 mg and 2 mg once daily for two sequential 2-week periods followed by 3 mg once daily for 12 weeks. Those aged 16 years and older received setmelanotide 2 mg once daily for 2 weeks followed by 3 mg once daily for 14 weeks.
The primary outcome was the proportion of patients achieving 5% or more BMI reduction from baseline after 16 weeks of treatment. Secondary outcomes included clinically meaningful BMI z score changes, weight loss, change in daily hunger scores and safety.
At 16 weeks, setmelanotide treatment led to a 12.6% body weight reduction and 14.5% BMI reduction. Researchers observed a mean BMI z score reduction from 3.9 to 2.7 at week 16 to baseline, and mean body weight was reduced to 90.4 kg, which was a 12.6% reduction from baseline.
Most patients (77.7%) achieved a BMI reduction of 10% or more throughout the study period. Regarding daily hunger score, the 11 patients aged 12 years or older experienced a mean change of –2.9 points or –45%.
Researchers also conducted a long-term extension of this study with all patients who had 5% or more BMI reduction. Of these patients, 12 reached a total of 29 weeks on setmelanotide therapy, and the mean BMI percent change was 21.1%. Five of these patients reached a total of 41 weeks on setmelanotide therapy, and the mean BMI percent change was –26.7%.
Overall, 83.3% of patients experienced treatment-related adverse events with the most frequent being nausea (61.1%) followed by vomiting (33.3%), skin hyperpigmentation (33.3%), diarrhea (22.2%) and COVID-19 (22.2%). Two patients discontinued setmelanotide treatment due to adverse events.
“A larger placebo-controlled clinical trial is necessary to confirm these data,” Roth said. “And what would be necessary is also to understand better who is responding to treatment. So, it would be very important to look at the different phenotypes and individual response to treatment.”
Setmelanotide recently received FDA breakthrough therapy designation for patients with hypothalamic obesity. At ObesityWeek, Rhythm Pharmaceuticals also announced initiation of a phase 3 trial of setmelanotide in early 2023 enrolling 120 patients aged 4 years or older for 60 weeks to further evaluate percent change in BMI compared with placebo.
Reference:
- Rhythm Pharmaceuticals Presents Data from Phase 2 and Long-term Extension Trial Evaluating Setmelanotide for the Treatment of Hypothalamic Obesity at ObesityWeek and Plans to Initiate Phase 3 Trial in Early 2023. Published Nov. 2, 2022. Accessed Nov. 2, 2022.
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Roth CL, et al. Poster 176. Presented at: ObesityWeek; Nov. 1-4, 2022; San Diego.
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