FDA Grants Breakthrough Therapy Designation for Hypothalamic Obesity to Rhythm’s Setmelanotide

Rare Daily Staff

The U.S. Food and Drug Administration granted Breakthrough Therapy designation for Rhythm Pharmaceuticals’ setmelanotide 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, chair, president, and CEO 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 percent, 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 melanocortin-4 receptor 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.

Photo: David Meeker, chair, president, and CEO of Rhythm