Rhythm Pharma gets orphan drug designation for its setmelanotide to treat hypothalamic obesity in Japan (2025)

Rhythm Pharmaceuticals, Inc, a global commercial-stage biopharmaceutical company focused on transforming the lives of patients living with rare neuroendocrine diseases, announced it has received orphan drug designation from Japan’s Ministry of Health, Labour and Welfare (MHLW) for setmelanotide as a treatment for acquired hypothalamic obesity.

Setmelanotide is a melanocortin-4 receptor (MC4R) agonist designed to treat hyperphagia and obesity. Rhythm is evaluating setmelanotide in a global phase 3 trial in patients with acquired hypothalamic obesity, with topline data on track to be disclosed in the second quarter of 2025.

“Orphan drug designation points to the need for therapeutic options for people living with acquired hypothalamic obesity,” said Yann Mazabraud, executive vice president, head of international at Rhythm Pharmaceuticals. “With this designation now in place in Japan, as well as in Europe, we believe we are well positioned to execute on our global strategy to bring patients with hypothalamic obesity the first-ever treatment targeting the underlying biology of this disease, pending success of our phase 3 trial and subsequent regulatory filings.”

Acquired hypothalamic obesity is a disease characterized by accelerated and sustained change in weight trajectory caused by an injury to the hypothalamus, often accompanied by hyperphagia (pathological, insatiable hunger and impaired satiety accompanied by abnormal food-seeking behaviors) and/or decreased energy expenditure. Acquired hypothalamic obesity most frequently follows hypothalamic injury from the growth or surgical removal of craniopharyngioma, astrocytoma, or other rare brain tumors. Additional causes of injury may include traumatic brain injury, stroke, or inflammation due to infection.

“There is a significant unmet medical need in Japan for a safe and effective precision medicine for patients living with acquired hypothalamic obesity, said Prof. Arima, Professor of the Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine. “Setmelanotide could provide new hope to these patients and their families.”

In Japan, drugs can be designated as orphan drugs if they treat diseases affecting fewer than 50,000 patients in Japan and there is a high medical need. Rhythm estimates there are 5,000 to 8,000 people living with acquired hypothalamic obesity in Japan, 5,000 to 10,000 people living with acquired hypothalamic obesity in the US, and 3,500 to 10,000 people living with acquired hypothalamic obesity in the EU.

Rhythm Pharmaceuticals’ lead asset, Imcivree (setmelanotide), an MC4R agonist designed to treat hyperphagia and severe obesity, is approved by the US Food and Drug Administration (FDA) to reduce excess body weight and maintain weight reduction long term in adult and pediatric patients 2 years of age and older 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), deficiency or leptin receptor (LEPR) deficiency. Both the European Commission (EC) and the UK’s Medicines & Healthcare Products Regulatory Agency (MHRA) have authorized setmelanotide for the treatment of obesity and the control of hunger associated with genetically confirmed BBS or genetically confirmed loss-of-function biallelic POMC, including PCSK1, deficiency or biallelic LEPR deficiency in adults and children 2 years of age and above. Additionally, Rhythm is advancing a broad clinical development program for setmelanotide in other rare diseases, as well as investigational MC4R agonists LB54640 and RM-718, and a preclinical suite of small molecules for the treatment of congenital hyperinsulinism. Rhythm’s headquarters is in Boston, MA.

In the United States, setmelanotide is indicated to reduce excess body weight and maintain weight reduction long term in adult and pediatric patients aged 2 years and older with syndromic or monogenic obesity due to Bardet-Biedl syndrome (BBS) or Pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency as determined by an FDA-approved test demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS). In the European Union and the United Kingdom, setmelanotide is indicated for the treatment of obesity and the control of hunger associated with genetically confirmed BBS or loss-of-function biallelic POMC, including PCSK1, deficiency or biallelic LEPR deficiency in adults and children 2 years of age and above. In the European Union and the United Kingdom, setmelanotide should be prescribed and supervised by a physician with expertise in obesity with underlying genetic etiology.