Setmelanotide leads to significant decrease in BMI for patients with hypothalamic obesity
Key takeaways:
- Participants receiving setmelanotide had a 19.8% greater BMI decrease than those assigned placebo at 1 year.
- More than half of the setmelanotide group had a BMI reduction of at least 15% during the trial.
A group of children and adults with hypothalamic obesity receiving setmelanotide for 1 year had nearly a 20% greater BMI reduction than those receiving placebo, according to top-line results released by Rhythm Pharmaceuticals.
As Healio previously reported, setmelanotide (Imcivree, Rhythm Pharmaceuticals) is a melanocortin-4 receptor agonist that the FDA approved for individuals with pro-opiomelanocortin (POMC) deficiency, proprotein convertase subtilisin/kexin type 1 (PCSK1) deficiency and leptin receptor (LEPR) deficiency in 2020; and for people with Bardet-Biedl syndrome in 2022. New top-line data from the phase 3 TRANSCEND trial revealed the medication also induces a statistically significant BMI reduction for people with hypothalamic obesity, a rare form of obesity that develops due to impaired signaling in the melanocortin-4 receptor pathway in the brain, which can lead to hyperphagia, reduced energy and weight gain, according to slides from Rhythm Pharmaceuticals that were presented on a conference call.
“There is an urgent need for effective treatments as current approaches [for hypothalamic obesity], including lifestyle interventions and pharmacotherapy intended for general obesity, have shown limited effectiveness in achieving long-term, durable weight loss,” Susan Phillips, MD, pediatric endocrinologist at Rady Children's Hospital-San Diego and professor of pediatrics at University of California San Diego School of Medicine, said in a press release. “These data are highly clinically meaningful, offering hope that a new targeted therapy may become available for patients — both adults and children — living with acquired hypothalamic obesity.”
TRANSCEND is a double-blind placebo-controlled trial where 120 patients (mean age, 19.9 years; 60% female) were randomly assigned 2:1 to receive once-daily setmelanotide (n = 81) or placebo (n = 39) for 1 year.
At 1 year, the setmelanotide group had a 16.5% decrease in BMI vs. a 3.3% BMI increase for the placebo group, leading to a placebo-adjusted greater BMI reduction of 19.8 percentage points with setmelanotide (P < .0001). Among 49 adults aged 18 years and older, those receiving setmelanotide had a larger BMI decrease than placebo by 19.2 percentage points (P < .0001), and among 71 children and adolescents younger than age 18 years, setmelanotide was associated with larger BMI reduction than placebo by 20.2 percentage points (P < .0001).
Of all participants receiving setmelanotide, 80% lowered their BMI by at least 5%, 63% had a BMI decrease of at least 10%, 51% reduced their BMI by at least 15% and 43% cut their BMI by at least 20% at 1 year (P vs. placebo for all < .0001).
BMI decreases were even greater among those using a GLP-1. Among 16 participants who used a GLP-1 before the trial, the setmelanotide group had a greater BMI decrease than placebo of 24.7 percentage points. Of 15 participants using a GLP-1 during the trial, those receiving setmelanotide had a greater loss in BMI than those receiving placebo by 27.1 percentage points.
Of participants aged 12 years and older, those receiving setmelanotide reported a greater reduction in hunger score from baseline to 1 year than those in the placebo group (P < .003).
According to a press release from Rhythm Pharmaceuticals, setmelanotide’s safety profile in TRANSCEND was similar to what was observed in previous trials. Adverse events that occurred in 20% or more of those receiving setmelanotide were skin hyperpigmentation (55.6%), nausea (50.6%), headache (39.5%), vomiting (39.5%), diarrhea (23.5%) and injection site reaction (23.5%). One serious adverse event related to the drug occurred. The event was hypernatremia that resolved after 2 days. No serious adverse events leading to study discontinuation were reported.
According to Rhythm Pharmaceuticals, 101 TRANSCEND participants are enrolled in an open-label extension study as of April 3. Full results from the trial will be presented at an upcoming medical conference, according to the company.
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