FDA Grants Rhythm Rare Pediatric Disease Designation for Rare Obesities Drug

Rare Daily Staff

The U.S. Food and Drug Administration has granted Rare Pediatric Disease designations to setmelanotide, Rhythm Pharmaceuticals’ experimental therapy for two rare obesity disorders.

Pro-opiomelanocortin (POMC) deficiency obesity is a disorder caused by variants in the POMC or PCSK1 genes that can often lead to severe obesity beginning early in life, insatiable hunger, endocrine abnormalities, including adrenocorticotropic hormone deficiency and mild hypothyroidism, red hair and light skin pigmentation. Leptin receptor (LEPR)deficiency obesity is a disorder caused by variants in the LEPR gene that can often lead to severe obesity beginning early in life, insatiable hunger, and endocrine abnormalities, including hypogonadotropic hypogonadism and hypothyroidism.

Setmelanotide activates MC4R, part of the key biological pathway that independently regulates hunger and body weight. Variants in genes within the MC4R pathway are associated with unrelenting hunger and severe, early-onset obesity.

In August 2019, Rhythm announced positive topline results from the pivotal cohorts in its two phase 3 clinical trials evaluating setmelanotide for the treatment of POMC and LEPR deficiency obesities. Both trials met their primary endpoints and all key secondary endpoints, demonstrating a statistically significant and clinically meaningful reduction in weight loss and reductions in insatiable hunger, or hyperphagia, in patients with POMC and LEPR deficiency obesities.

In June 2020, Rhythm announced new data from eight supplemental patients, including four pediatric patients aged 6-12, who subsequently enrolled in its two pivotal phase 3 clinical trials for POMC and LEPR deficiency obesities. All eight supplemental patients, four of whom had POMC deficiency obesity and four of whom had LEPR deficiency obesity, achieved the primary endpoint of 10 percent or greater weight loss at 52 weeks on setmelanotide therapy, as calculated under the statistical analysis plan.

“As a result of early-onset, severe obesity and insatiable hunger, many patients experience debilitating comorbidities beginning in childhood, which worsen over time and can greatly affect their quality of life,” said Murray Stewart, chief medical officer of Rhythm. “With setmelanotide, we believe we have the potential to modify this disease trajectory by delivering a therapy that can be dosed chronically beginning in childhood.”

The FDA grants Rare Pediatric Disease designation for serious or life-threatening diseases with manifestations in individuals aged from birth to 18 years, including access to the FDA’s expedited review and approval process. The designation makes setmelanotide eligible for a Rare Pediatric Disease Priority Review voucher upon approval of the therapy by the FDA.

The vouchers can be used to reduce the time of an FDA new drug approval review to six months from ten months. The vouchers are potentially lucrative because they are transferable. Most recently, Sarepta sold its priority review voucher to Vifor Pharma $111 million in February 2020.

The FDA has accepted Rhythm’s NDA for setmelanotide for the treatment of POMC and LEPR deficiency obesities for filing, granted Priority Review and assigned marketing decision goal date of November 27, 2020. Rhythm submitted a MAA for setmelanotide to treat individuals living with POMC deficiency obesity or LEPR deficiency obesity to the European Medicines Agency in June 2020.

Photo: Murray Stewart, chief medical officer of Rhythm

Editor’s note: This story was updated to correct the most recent sales of a priority review voucher.