People with Bardet-Biedl syndrome lower metabolic syndrome score with setmelanotide
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Key takeaways:
- Most adolescents and adults with Bardet-Biedl syndrome lowered their MetS-Z-BMI score at 1 year with setmelanotide.
- Those who achieved their weight-related threshold had a greater MetS-Z-BMI score reduction.
DALLAS — Setmelanotide may lower the risk for metabolic syndrome for people with a rare monogenic form of obesity, according to data presented at ObesityWeek.
As Healio previously reported, 32.3% of people with Bardet-Biedl syndrome lost at least 10% of their body weight at 1 year with setmelanotide (Imcivree, Rhythm Pharmaceuticals) in a phase 3 trial.
In new data from the trial, researchers found that setmelanotide therapy also was associated with reduced metabolic syndrome score based on BMI (MetS-Z-BMI score) at 1 year for people with Bardet-Biedl syndrome. Sonali Malhotra, MD, DABOM, medical director of medical affairs for Rhythm Pharmaceuticals and a board-certified pediatric endocrinologist at Massachusetts General Hospital in Boston, said the data show setmelanotide may have benefits beyond weight loss.
“[Setmelanotide] in this patient population may reduce the risk [for] future cardiovascular disease, metabolic syndrome and type 2 diabetes,” Malhotra said during a presentation.
Researchers collected data from 22 people with Bardet-Beidl syndrome who completed the phase 3 trial and had necessary data available to calculate MetS-Z-BMI score at baseline and 1 year (mean age, 20.3 years; 60.1% female). MetS-Z-BMI score is an estimate of one’s risk and severity of metabolic syndrome. Weight-threshold achievers were defined as adults who lost 10% or more body weight at 1 year or adolescents who decreased their BMI z score by 0.3 or more points at 1 year.
Of the study population, 13 were adults aged 18 years and older and nine were children aged 10 to 18 years. At baseline, each 1-point increase in MetS-Z-BMI score increased the risk for CVD (OR = 3.1) and type 2 diabetes (OR = 3.7) for adults. Similarly, adolescents had an increased risk for CVD (OR = 10.2) and type 2 diabetes (OR = 2.8) with each 1-point increase in MetS-Z-BMI score at baseline.
Seventeen of the 22 participants had a decrease in MetS-Z-BMI score at 1 year. A greater MetS-Z-BMI score decrease was observed at 1 year for those who were weight threshold achievers compared with nonachievers (mean change, –0.64 points vs. 0.08 points; P = .0043).
“Despite not meeting the weight-related clinical response thresholds or benchmarks, five out of nine of those clinical nonachiever patients exhibited a reduction in their MetS-Z-BMI scores, which highlight the potential that setmelanotide or melancortin-4 receptor therapies can have some beneficial impacts on these patients beyond weight loss alone,” Malhotra said. “It is important to understand ... the holistic approach with these patients beyond weight loss, beyond these [weight] threshold markers. These are just slight pointers in those directions of assessing the change beyond weight loss.”
There were no differences in MetS-Z-BMI score between males and females, adolescents and adults or when participants were stratified by Bardet-Biedl syndrome subtype.
The findings for people with Bardet-Biedl syndrome were similar to what was observed in a group of people with obesity due to proopiomelanocortin (POMC) deficiency or leptin receptor (LEPR) deficiency. As Healio previously reported from ObesityWeek, children and adults with one of those two rare monogenic forms of obesity who received setmelanotide also had decreases in MetS-Z-BMI score at 1 year.
“Further work is needed and is being conducted to better understand the degree of improvements in metabolic syndrome with setmelanotide observed in patients with monogenic and syndromic forms of obesity,” Malhotra said.
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Haqq AM, et al. Oral-066. Presented at: ObesityWeek; Oct. 14-17, 2023; Dallas.
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