Rhythm Pharmaceuticals announced that it has completed enrollment of the pivotal cohorts of 10 patients in two separate, ongoing, registration-enabling Phase 3 clinical trials evaluating setmelanotide in pro-opiomelanocortin (POMC) and leptin receptor (LEPR) deficiency obesity. POMC and LEPR deficiency obesity are two ultra-rare genetic disorders that result in excess hunger, also known as hyperphagia, and severe, early-onset obesity. Setmelanotide is a first-in-class melanocortin-4 receptor (MC4R) agonist, for which the U.S. Food and Drug Administration (FDA) has granted both Breakthrough Therapy Designation and Orphan Drug Designation in POMC and LEPR deficiency obesity.
Rhythm expects to report initial data from the Phase 3 trials of both POMC and LEPR deficiency obesity in the third quarter of 2019. Rhythm then plans to submit concurrent New Drug Application (NDA) filings to the FDA for setmelanotide in patients with these indications based on one-year data from these pivotal cohorts of 10 patients. In addition, the Company plans to continue enrolling supplemental patients in both trials who may not complete one year of treatment at the time of NDA filing, including patients between six and 11 years of age, to provide additional data regarding the use of setmelanotide in people living with POMC and LEPR deficiency obesity.
“Patients with MC4R pathway deficiencies represent an underdiagnosed population, whose early-onset obesity and excess hunger impairs their lives,” said Keith Gottesdiener, M.D., Chief Executive Officer of Rhythm. “Completing enrollment in both of our pivotal Phase 3 trials in POMC and LEPR deficiency obesity marks a key milestone for Rhythm and for people living with these rare genetic disorders, as it brings us one step closer to our goal of providing setmelanotide as a first-in-class therapy that has the potential to reestablish both weight and appetite control. We are particularly encouraged to have completed enrollment ahead of schedule in our LEPR deficiency obesity trial, which speaks to the significant need for a new, disease-modifying therapy, and which we anticipate will allow us to submit concurrent NDA filings in POMC and LEPR deficiency obesity and potentially to accelerate the availability of setmelanotide for LEPR patients. We look forward to further evaluating setmelanotide’s therapeutic potential as we progress our ongoing studies and work to more broadly understand the benefits of setmelanotide, including in the pediatric setting.”
The open-label, single-arm, multinational Phase 3 trials evaluating the safety and efficacy of setmelanotide in POMC and LEPR deficiency obesity share the same trial design. The primary endpoint in both trials is a responder analysis for weight, defined as patients achieving a 10 percent change from baseline. The first secondary endpoint in both trials is the mean percentage change in weight. Hunger scores are also key secondary endpoints.
Rhythm is also evaluating setmelanotide in four additional rare genetic disorders of obesity. Rhythm expects to initiate a Phase 3 study evaluating setmelanotide in Bardet-Biedl Syndrome in 2018. The Company has treated a number of the first patients in a Phase 2 proof-of-concept basket study evaluating setmelanotide in Alström Syndrome, POMC epigenetic disorders and POMC heterozygous deficiency obesity and expects to announce initial data in each indication in the second quarter of 2018. In addition, Rhythm has launched efforts to build a patient registry, Tracing the Effect of the MC4R Pathway in Obesity (TEMPO), and is supporting The Genetic Obesity Project and the Go-ID Genotyping Study.