Setmelanotide Shows Promise in Reducing Obesity in Young Children with Rare Genetic Deficiencies
Key Insights
A Phase 3 trial of setmelanotide in children aged 2-5 with BBS, POMC (search), PCSK1 (search), or LEPR (search) deficiency demonstrated clinically meaningful reductions in BMI Z-score.
83% of patients achieved a ≥0.2-point reduction in BMI Z-score after 52 weeks of treatment with setmelanotide, indicating significant weight management benefits.
Caregivers reported a 91% reduction in patient hunger compared to baseline, alongside a reduced sense of personal burden, highlighting improved quality of life.
Rhythm Pharmaceuticals announced the publication of results from its Phase 3 VENTURE trial in The Lancet Diabetes & Endocrinology, demonstrating the efficacy and safety of setmelanotide in children aged 2 to under 5 years with Bardet-Biedl syndrome (BBS) or pro-opiomelanocortin (POMC (search)), proprotein convertase subtilisin/kexin type 1 (PCSK1 (search)), or leptin receptor (LEPR (search)) deficiency. The study highlights the potential of early intervention with setmelanotide to address severe obesity (search) and hyperphagia in this vulnerable population.
The open-label, 52-week Phase 3 VENTURE trial enrolled 12 patients to evaluate setmelanotide in patients aged 2 to younger than 6 years with BBS or POMC (search), PCSK1 (search) or LEPR (search) deficiency. The trial's co-primary endpoints were changes in BMI Z-score and hunger levels. Clinically meaningful improvements were observed in both co-primary endpoints at week 52.
Key Findings from the VENTURE Trial
The study revealed that 10 of 12 patients (83%) achieved a ≥0.2-point reduction in body mass index (BMI) Z-score. The mean percent change in BMI from baseline was -18%. Furthermore, 91% of caregivers reported that patients had reduced hunger compared with baseline, and the caregivers also reported feelings of reduced personal burden.
"Severe, early-onset obesity (search) has a negative short-term and long-term impact on a child’s health," said Professor Jesús Argente, M.D., Ph.D., Department of Pediatrics and Pediatric Endocrinology, Hospital Infantil Universitario Niño Jesús and Universidad Autónoma de Madrid, Madrid, Spain. "In this study, setmelanotide demonstrated clinically meaningful reductions in hunger and body weight in patients younger than 5 years of age with severe obesity. We believe these data support the use of this targeted therapy in a patient population that could benefit from intervention as early as possible."
Safety and Tolerability
Setmelanotide was generally well-tolerated. No serious adverse events (AEs) leading to study discontinuation or death were reported. The most common treatment-emergent AEs were skin hyperpigmentation (75%), vomiting (58%), nasopharyngitis (42%), upper respiratory tract infection (33%), and injection site bruising (33%).
Regulatory Landscape
In July 2024, IMCIVREE (setmelanotide) received authorization in the European Union for control of hunger and treatment of obesity (search) in adults and children as young as 2 years old, living with BBS or POMC (search), PCSK1 (search), or LEPR (search) deficiency. Rhythm has completed submission of its supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) to expand the label of IMCIVREE to treat pediatric patients between the ages of 2 and younger than 6 years old in approved indications in the United States. The FDA has granted Priority Review of the sNDA and assigned a Prescription Drug User Fee Act (PDUFA) goal date of December 26, 2024.