FDA
Imcivree now FDA-approved for acquired hypothalamic obesity
On March 19, 2026, FDA approved a new indication for Imcivree (setmelanotide): to reduce excess body weight and maintain reduction long term in adults and pediatric patients aged 4 years and older with acquired hypothalamic obesity (HO). Imcivree is the first FDA-approved treatment for this condition.
Efficacy
Approval was based on the double-blind, placebo-controlled, phase 3 TRANSCEND trial (NCT05774756), in which patients aged 4 years and older with acquired HO were randomized 2:1 to receive once‑daily subcutaneous setmelanotide—titrated to 1.5–3 mg based on age, weight, and tolerability—or placebo. A 4-to-8-week dose titration period was followed by a 52-week treatment period. A total of 142 patients were randomized and analyzed in the study; 47% were adults, 31% were 12 to 17 years old, and 23% were 4 to 11 years old; 40% were male; 75% were White, 11% were Asian, 5% were Black or African American, and 9% had an unknown or not reported race; 11% were Hispanic or Latino ethnicity and less than 1% had an unknown or not reported ethnicity; and mean BMI was 36 kg/m2 (range, 21-70 kg/m2).
The primary endpoint was mean percent change in body mass index (BMI) from baseline to 52 weeks. Results showed patients treated with setmelanotide (n=94) experienced a mean 15.84% reduction in BMI at week 52, while the placebo group (n=48) showed a 2.55% BMI increase, representing an 18.4% placebo-adjusted reduction (95% confidence interval: -21.94, -14.85).
Safety
Most common adverse reactions (≥5% and greater than placebo) in patients with acquired HO were skin hyperpigmentation, nausea, vomiting, headache, melanocytic nevus, constipation, dizziness, oropharyngeal pain, gastroenteritis, ear infection, spontaneous penile erection, acute adrenal insufficiency, and sodium imbalance. The prescribing information for Imcivree also has warnings regarding hypersensitivity reactions and depression/suicidal ideation.
Recommended dose
The recommended starting dose is 0.5 mg subcutaneously once daily for 2 weeks. The maintenance dose for pediatric patients aged 4 years to less than 6 years old is weight-based. For adults and pediatric patients aged 6 years and older, the maintenance dose is 3 mg subcutaneously once daily. See prescribing information for recommended titration.
Sources:
(2026, March 19). Rhythm Pharmaceuticals Announces FDA Approval of IMCIVREE (setmelanotide) for Patients with Acquired Hypothalamic Obesity. [Press release]. https://ir.rhythmtx.com/news-releases/news-release-details/rhythm-pharmaceuticals-announces-fda-approval-imcivreer-1
Imcivree (setmelanotide). [Package insert]. https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/213793s009lbl.pdf Revised March 2026. Accessed March 24, 2026.