Completed enrollment of 10 patients in 2 separate, ongoing, and pivotal cohorts in phase 3 clinical trials for the evaluation of setmelanotide in pro-opiomelanocortin (POMC) and leptin receptor (LEPR) deficiency obesity has been achieved, according to Rhythm Pharmaceuticals, Inc.
Setmelanotide is a first-in-class melanocortin-4 receptor (MC4R) agonist.
POMC and LEPR deficiency obesity are two ultra-rare genetic disorders characterized by excess hunger (hyperphagia), and severe, early-onset obesity.
According to Rhythm sources, initial data from the phase 3 trials of both POMC and LEPR deficiency obesity are expected in the third quarter of 2019. Following the report, Rhythm plans to use the 1-year data from these pivotal cohorts of 10 patients in order to submit concurrent New Drug Application (NDA) filings to the FDA for setmelanotide in patients with POMC and LEPR deficiency obesity.
In order to acquire additional data regarding the use of setmelanotide in those living with POMC and LEPR deficiency obesity, both trials will also plan to continue enrolling supplemental patients who may not complete 1 year of treatment at the time of NDA filing. These supplemental patients between the ages of 6 and 11 years of age.
In addition, the same trial design is shared between the open-label, single-arm, multinational phase 3 trials evaluating the safety and efficacy of setmelanotide in POMC and LEPR deficiency obesity. A responder analysis for weight, defined as patients achieving a 10% change from baseline, will serve as the primary endpoint for both trials. Prime secondary endpoints in both trials include the mean percentage change in weight and hinger scores.
“Patients with MC4R pathway deficiencies represent an underdiagnosed population, whose early-onset obesity and excess hunger impairs their lives,” stated Keith Gottesdiener, MD, chief executive officer of Rhythm, in a recent statement
. “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."
In 4 additional rare genetic disorders of obesity, Rhythm is also evaluating setmelanotide. A phase 3 study evaluating setmelanotide in Bardet-Biedl Syndrome is expected to initiate in 2018.
In a phase 2 proof-of-concept basket study evaluating setmelanotide in Alström Syndrome, POMC epigenetic disorders and POMC heterozygous deficiency obesity, Rhythm has treated a number of the first patients. Initial data announcements pertaining to each indication are expected in the second quarter of 2018.
Additionally, a patient registry, Tracing the Effect of the MC4R Pathway in Obesity (TEMPO), has been launched by Rhythm in an effort to help build and support The Genetic Obesity Project
and the Go-ID Genotyping Study
“We are particularly encouraged to have completed enrollment ahead of schedule in our LEPR deficiency obesity trial,” added Dr Gottesdiener, “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.”
Previously. the US Food and Drug Administration (FDA) granted both Breakthrough Therapy Designation and Orphan Drug Designation to setmelanotide for POMC and LEPR deficiency obesity.