Rhythm Receives Rare Pediatric Disease Designation for POMC, LEPR Deficiency Obesity Treatment

Rhythm Pharmaceuticals announced the U.S. Food and Drug Administration (FDA) has granted rare pediatric disease designations for setmelanotide, an investigational melanocortin-4 receptor (MC4R) agonist, for the treatment of pro-opiomelanocortin (POMC) deficiency obesity and leptin receptor (LEPR) deficiency obesity. As previously announced, the Company’s New Drug Application (NDA) for setmelanotide was accepted for filing with priority review by the FDA and assigned a Prescription Drug User Fee Act (PDUFA) goal date of November 27, 2020.

Under the FDA's rare pediatric disease designation and voucher programs, the FDA may grant a priority review voucher to a sponsor who receives a product approval for a “rare pediatric disease,” which is defined as a serious or life-threatening disease in which the serious or life-threatening manifestations primarily affect individuals aged from birth to 18 years and affects fewer than 200,000 people in the U.S. Subject to FDA approval of setmelanotide for the treatment of POMC and LEPR deficiency obesities, Rhythm would be eligible to receive one priority review voucher, which could then be redeemed to receive priority review for any subsequent marketing application, or sold or transferred to other companies for their programs.

“We believe that receipt of the rare pediatric disease designation for setmelanotide, for which we have previously received Breakthrough Therapy and orphan drug status, underscores the FDA’s recognition of setmelanotide’s potential to treat POMC and LEPR deficiency obesities; two serious, ultra-rare conditions for which existing treatment options are woefully inadequate,” said Murray Stewart, M.D., Chief Medical Officer of Rhythm. “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. 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. We are grateful to the FDA for this designation and look forward to continuing to work toward our goal of delivering setmelanotide to people with rare genetic disorders of 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.

POMC and LEPR deficiency obesities are ultra-rare genetic disorders. Rhythm believes both disorders are underdiagnosed, and estimates there are approximately 100 to 500 patients in the U.S. with POMC deficiency obesity and approximately 500 to 2,000 patients in the U.S. with LEPR deficiency obesity. POMC deficiency obesity is a disorder caused by variants in the POMC or PCSK1 genes that can often lead to severe obesity beginning in childhood and insatiable hunger, in addition to endocrine abnormalities, and sometimes red hair and light skin pigmentation. LEPR deficiency obesity is a disorder caused by variants in the LEPR gene that can often lead to severe obesity beginning early in life and insatiable hunger, in addition to endocrine abnormalities. Most patients with POMC or LEPR deficiency obesity experience exponential weight gain in the first months of life, which continues rapidly over the course of their lives. This weight gain cannot be mitigated by diet, exercise or other lifestyle changes, or by existing therapeutic interventions.