ADC Reviews

FDA Breakthrough Therapy Designation for Hypothalamic Obesity Drug Setmelanotide


On November 1, Rhythm Pharmaceuticals announced that its MC4R agonist setmelanotide was granted Breakthrough Therapy Designation by the FDA for the treatment of hypothalamic obesity.

The FDA’s Breakthrough Therapy designation is designed to expedite the development and review of a drug to address a serious disease with an unmet medical need that, based on preliminary clinical evidence, may demonstrate relative relative performance on one or more clinically meaningful endpoints Substantial improvement from existing treatments.

Previously, the company announced positive results from a Phase II clinical study, which showed that after 16 weeks of treatment, the BMI (body mass index) of evaluable patients in the setmelanotide group decreased by more than 5%, and the BMI decreased by an average of 17.2%.

Hypothalamic obesity is a rare form of acquired extreme obesity that usually follows damage to the hypothalamic region of the brain that may affect the function of the melanocortin 4 receptor (MC4R) signaling pathway. The MC4R signaling pathway is a pathway responsible for controlling important physiological functions such as hunger and weight regulation. Clinically, hypothalamic obesity is more common in patients with craniopharyngiomas, astrocytomas, and other rare brain tumors, and these patients may develop hypothalamic obesity even after surgical resection of the tumor – in the tumor In the first 6 to 12 months after excision, there is rapid weight gain, decreased energy expenditure, increased hunger, and eventually severe obesity.

Setmelanotide, a “First-in-class” melanocortin-4 receptor (MC4R) agonist, was first approved by the FDA in November 2020 and launched in Europe in July 2021. So far, 4 Item adaptations, including chronic disease in obese adults and children (over 6 years of age) due to genetic deficiencies in proopiomelanocortin (POMC), proprotein convertase subtilisin 1 (PCSK1), or leptin receptor (LEPR) Weight management and treatment of Budd-Bidde syndrome.