FDA Approves Expanded Indication for Setmelanotide to Include Patients 2 and Older

The FDA approved an expanded indication for setmelanotide (Imcivree; Rhythm Pharmaceuticals Inc) to include children 2 years and older. The treatment is indicated to reduce excess body weight and maintain weight reduction long-term for patients with syndromic or monogenic obesity due to Bardet-Biedl syndrome (BBS) or genetically confirmed pro-opiomelanocortin (POMC), including proprotein convertase subtilisin/kexin type 1 (PCSK1) or leptin receptor (LEPR) deficiency, according to a news release.¹

FDA Approval, Weight Loss, Pediatrics | Image Credit: Aquir | stock.adobe.com

“It’s important to understand that rare MC4R pathway diseases differ from general obesity as the insatiable hunger these patients experience is pathologic and a result of impairment to a pathway in the brain. With this insatiable hunger, most patients develop early-onset obesity before the age of 5,” Ilene Fennoy, MD, MPH, pediatric endocrinologist, obesity specialist, and professor of Pediatrics at Columbia University Medical Center, said in the news release. “Obesity in childhood, if untreated, can lead to a greater risk of severe and long-term health complications, making early intervention to treat obesity critical. With this expanded indication for Imcivree, patients now can receive a much needed, targeted treatment that we believe can address a root cause of their obesity at a very young age.”¹

The expanded approval is due to clinical trial results that were published in The Lancet Diabetes & Endocrinology in November 2024, demonstrating significant and sustained reductions in measures of both weight and hunger. The trial (NCT04966741) was a phase 3 open-label clinical study that evaluated the efficacy, safety, and tolerability of the treatment over a 1-year period for individuals aged 2 to under 6 years of age. Investigators included individuals with obesity due to BBS or POMC, PCSK1, LEPR deficiency, were between 2 and less than 6 years at time of enrollment, obesity, defined as body mass index in the 97th or higher percentile for age and gender, symptoms of hyperphagia, and a parent or guardian consenting to the study. Those with liver disease, family history of melanoma, or uncontrolled endocrine, metabolic, or medical condition known to impact body weight were excluded.^1,2

The primary outcomes included percentage of individuals with greater than or equal to a 0.2 reduction of BMI score from baseline to week 52 and mean percent change from baseline in BMI to week 52. Secondary outcomes included mean absolute change from baseline BMI, mass change from baseline, mean change from baseline in bone age, change from baseline in body weight, number of treatment-emergent adverse events (TEAEs), and number of TEAEs by grade severity.²

In the study, investigators found that 10 of 12 of the individuals reached a 0.2-point reduction in BMI score at week 52, and there was a mean percent change of –19% in the overall safety population. For POMC or LEPR deficiency, there was a –26% change and a –10% change for those with BBS.³

“Many children with BBS feel hungry or think about food regardless of how much or how recently they've eaten, leaving families to deal with children sneaking or stealing food, which makes daily life extremely stressful. Parents have enough to worry about and manage when their child has a multi-systemic syndrome like BBS and Imcivree can be an important tool for their obesity,” Tim Ogden, President of the Bardet Biedl Syndrome Foundation, said in the news release.¹

According to the news release, the drug initially received FDA approval in November 2020, specifically for patients 6 years and older with POMC, PCSK1, or LEPR deficiencies and another approval in June 2022 for those with BBS.¹

REFERENCES

1. Rhythm Pharmaceuticals Announces FDA Approval of IMCIVREE (setmelanotide) for Patients as Young as 2 Years Old. News release. Rhythm Pharmaceuticals. December 20, 2024. Accessed December 20, 2024. https://www.globenewswire.com/news-release/2024/12/20/3000811/0/en/Rhythm-Pharmaceuticals-Announces-FDA-Approval-of-IMCIVREE-setmelanotide-for-Patients-as-Young-as-2-Years-Old.html

2. Setmelanotide in Pediatric Participants With Rare Genetic Diseases of Obesity. ClinicalTrials.gov ID: NCT04966741. Updated November 27, 2024. Accessed December 20, 2024. https://clinicaltrials.gov/study/NCT04966741

3. Argente J, Verge CF, Okorie U, et al. Setmelanotide in patients aged 2-5 years with rare MC4R pathway-associated obesity (VENTURE): a 1 year, open-label, multicenter, phase 3 trial. Lancet Diabetes Endocrinol. Published online November 12, 2024. doi:10.1016/S2213-8587(24)00273-0