Real-world data show lower BMI, hunger in children with acquired HO
French findings extended to 18 months; metabolic risk scores also improved
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Some treatments for acquired hypothalamic obesity are given by injection. (Image from iStock)
The approved therapy Imcivree (setmelanotide) was associated with reduced hunger and improvements in weight-related measures among children with acquired hypothalamic obesity (aHO) in a real-world analysis from France.
These and other Imcivree findings were presented at the 64th Annual European Society for Paediatric Endocrinology Meeting, held earlier this month in Marseille, France. The research was funded by Rhythm Pharmaceuticals, the company that markets Imcivree.
“Patients with [aHO] often experience severe obesity, persistent hyperphagia [incontrollable hunger] and metabolic complications that can significantly affect their health and daily lives,” David Meeker, MD, Rhythm’s chairman, CEO, and president, said in a company press release. “Real-world data from France show that [Imcivree] is associated with sustained improvements in BMI [body mass index] and hunger … for up to 18 months [about 1.5 years].” BMI is a measure based on weight and height commonly used as a proxy for body fat.
Imcivree approved for aHO in patients ages 4 and older
aHO is marked by damage to the hypothalamus, a part of the brain that helps regulate hunger, energy balance, and body weight. People with the disease often experience hyperphagia, or excessive, persistent hunger, which can contribute to rapid weight gain.
Imcivree is a daily injection therapy designed to restore disrupted signals involved in controlling hunger and body weight. The therapy is approved in the U.S. and Europe for aHO patients ages 4 and older. The therapy was also recently approved for aHO in Japan, where Rhythm expects to launch it before the end of 2026, pending final pricing.
In France, Imcivree was available through a pre-marketing early-access program before its approval.
In a poster titled “Paediatric Patients with Acquired Hypothalamic Obesity Treated with Setmelanotide: Real-World BMI and Hunger Data for up to 18 Months in France,” researchers presented data from 30 children with aHO who started Imcivree through the program and were followed for up to 18 months.
To track changes in weight, researchers measured body mass index (BMI), a measure based on height and weight. BMI decreased from baseline among evaluable patients, by an average of 11.5% at six months, 13.4% at nine months, 10.5% at one year, and 9% at 1.5 years.
At all time points, more than 88% of children experienced a clinically meaningful reduction of at least 0.2 points in BMI z-score, which reflects how much a child’s BMI differs from the average for children of the same age and sex.
Patient-reported hunger was assessed in participants ages 12 to younger than 18. Available data showed that average hunger scores were lower than before treatment at six, 12, and 18 months.
Real-world safety findings matched known Imcivree profile
Safety data from this real-world study in France were consistent with Imcivree’s known profile. Among the 24 patients with available adverse-event data, the most commonly reported adverse events were injection-site reactions (29.2%) and skin hyperpigmentation (20.8%).
“This real-world data from paediatric patients with aHO who were treated with [Imcivree] for up to 18 months showed improvements in BMI and hunger,” the researchers wrote, adding that these findings “support the real-world therapeutic value of [Imcivree] treatment for paediatric patients with aHO.”
Regulatory approvals of Imcivree were supported largely by data from the Phase 3 TRANSCEND clinical trial (NCT05774756), which tested the therapy against a placebo in 120 people with aHO ages 4 to 66. The study met its main goal of showing that Imcivree was better than the placebo at reducing BMI. The therapy also reduced hunger compared with placebo.
In a separate presentation titled “Impact of setmelanotide on metabolic index scores in paediatric participants with acquired hypothalamic obesity – A phase 3 trial post hoc analysis,” researchers shared data from TRANSCEND participants ages 4 to younger than 18 on changes in several measures of metabolic health.
Specific metabolic scores included metabolic syndrome severity z-BMI (MetS-Z-BMI), lipid accumulation product (LAP), and triglyceride-waist circumference index (TYG-WC). Lower MetS-Z-BMI scores are associated with lower metabolic syndrome severity and lower risks of type 2 diabetes and cardiovascular disease. Lower LAP scores are associated with lower risks of metabolic syndrome, type 2 diabetes, and cardiovascular disease, while lower TYG-WC values are associated with lower risks of death from any cause and from cardiovascular disease.
Results showed that the metabolic burden of these children was high at the study’s start. Imcivree resulted in significantly greater reductions in these scores. Imcivree also bested placebo at reducing scores linked to fat buildup in the liver and health risks related to fat around internal organs.
The researchers cautioned that many of these metabolic risk scores have not yet been validated for predicting future cardiovascular events in children. Still, the findings suggested that the therapy “may provide metabolic benefits beyond reductions in [hyperphagia] and body weight,” the researchers wrote.
These real-world and clinical trial data “provide a more comprehensive picture of the treatment’s impact in acquired hypothalamic obesity,” Meeker said.
