Rhythm Pharmaceuticals Announces Setmelanotide Granted Breakthrough Therapy Designation for Hypothalamic Obesity 

Rhythm Pharmaceuticals, Inc. recently announced that setmelanotide received Breakthrough Therapy Designation from the US FDA for the treatment of hypothalamic obesity.

The FDA’s Breakthrough Therapy Designation is designed to expedite development and review of medicines that aim to address a serious condition with an unmet medical need with preliminary clinical evidence indicating that the drug may demonstrate substantial improvement over existing treatments on one or more clinically significant endpoints.

“Breakthrough Therapy Designation marks a meaningful step in our effort to advance setmelanotide as quickly as possible for hypothalamic obesity, reflecting both the strength of our interim Phase 2 data and the significant need for a novel therapy that can transform the care of patients living with this rare, acquired obesity,” said David Meeker, MD, Chair, President and Chief Executive Officer of Rhythm. “We look forward to initiating a Phase 3 trial evaluating setmelanotide in hypothalamic obesity in early 2023.”

Hypothalamic obesity is a rare, acquired form of extreme obesity that occurs following damage to the hypothalamic region of the brain, which includes the MC4R pathway and is responsible for controlling physiological functions such as hunger and weight regulation. It most frequently follows the growth or surgical removal of craniopharyngioma, astrocytoma or other rare brain tumors. Patients experience rapid weight gain, a reduction in energy expenditure and increase in hunger in the first six to 12 months following tumor resection, and ultimately develop severe obesity. Rhythm estimates there are approximately 5,000-10,000 patients living with acquired hypothalamic obesity in the United States, with approximately 500 new cases each year.

Breakthrough Therapy Designation was granted based on results from a Phase 2, 16-week clinical study of setmelanotide. Rhythm announced positive interim results from this trial in July 2022, with preliminary data showing that all 11 evaluable patients achieved a BMI decrease of more than 5 percent, with a mean reduction in BMI of 17.2%, at 16 weeks on setmelanotide therapy. The Company will present full data from this trial in a late-breaking poster presentation at The Obesity Society’s ObesityWeek 2022.

Setmelanotide, an MC4R agonist marketed as IMCIVREE, previously received Breakthrough Designation while being developed for Bardet-Biedl syndrome and proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1) and leptin receptor (LEPR) deficiencies.

Rhythm is a commercial-stage biopharmaceutical company committed to transforming the lives of patients and their families living with hyperphagia and severe obesity caused by rare melanocortin-4 receptor (MC4R) pathway diseases. Rhythm’s precision medicine, setmelanotide, is approved by the US FDA for chronic weight management in adult and pediatric patients 6 years of age and older with monogenic or syndromic obesity due to pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1) or leptin receptor (LEPR) deficiency confirmed by genetic testing, or patients with a clinical diagnosis of Bardet-Biedl syndrome (BBS). The European Commission (EC) has 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 6 years of age and above.

The UK’s Medicines & Healthcare Products Regulatory Agency (MHRA) authorized setmelanotide for the treatment of obesity and the control of hunger associated with genetically confirmed loss-of-function biallelic POMC, including PCSK1, deficiency or biallelic LEPR deficiency in adults and children 6 years of age and above. Additionally, Rhythm is advancing a broad clinical development program for setmelanotide in other rare genetic diseases of obesity and is leveraging the Rhythm Engine and the largest known obesity DNA database — now with approximately 45,000 sequencing samples — to improve the understanding, diagnosis and care of people living with severe obesity due to certain genetic deficiencies. Rhythm’s headquarters is in Boston, MA.