RM 493 filed with MAA for pro-opiomelanocortin (POMC) deficiency obesity and leptin receptor (LEPR) deficiency obesity.- Rhythm Pharma

Rhythm Pharmaceuticals announced that it has submitted its Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for RM 493 (setmelanotide) for the treatment of pro-opiomelanocortin (POMC) deficiency obesity and leptin receptor (LEPR) deficiency obesity. The company has been granted accelerated assessment of the MAA, which potentially shortens review time by the Committee for Medicinal Products for Human Use (CHMP). In conjunction with this submission, Rhythm announced additional positive data from eight supplemental patients, including four pediatric patients, enrolled in its two pivotal Phase III clinical trials for POMC and LEPR deficiency obesities, as well as updated data from its long-term extension study of setmelanotide in patients with POMC or LEPR deficiency obesity. Rhythm included these data in its MAA submission package to the EMA. In August 2019, Rhythm announced positive topline results from the pivotal cohorts in its two Phase III 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 increase in weight loss and reductions in insatiable hunger, or hyperphagia, in patients with POMC and LEPR deficiency obesities. Rhythm enrolled a total of eight patients, including four pediatric patients between the ages 6 and 12 years old, in supplemental cohorts in its Phase III trials evaluating setmelanotide for the treatment of POMC deficiency obesity and LEPR deficiency obesity, with four supplemental patients enrolled in each trial. All eight supplemental patients achieved the primary endpoint of 10 percent or greater weight loss at 52 weeks on setmelanotide therapy, as calculated under the same statistical analysis plan used in the pivotal trials. All of the supplemental patients were enrolled by European investigators, as were most of the patients in the pivotal cohorts. The mean reduction in baseline body weight for the supplemental POMC deficiency obesity patients was -26.3 percent, and the mean reduction in body weight for the supplemental LEPR deficiency obesity patients was -13.2 percent. The estimated mean percentage reduction in most hunger score for evaluable patients in the supplemental cohorts was -57.3 percent. Hunger scores collected from children younger than 12 were calculated differently and therefore not counted in this analysis. Combining data from the eight supplemental patients with data from the pivotal cohorts, 12 out of 14 patients with POMC deficiency obesity and 9 out of 15 patients with LEPR deficiency obesity achieved the primary endpoints of greater than 10 percent weight loss over approximately one year. Additionally, the data for all key secondary endpoints from the supplemental cohorts were consistent with the data from the pivotal cohorts. A total of 15 patients who participated in the pivotal studies are being treated in the extension study, including nine living with POMC deficiency obesity and six living with LEPR deficiency obesity, all of whom previously completed one of Rhythm’s two pivotal Phase III trials evaluating setmelanotide for the treatment of severe obesity and insatiable hunger. Two additional patients who were enrolled in the LEPR deficiency obesity pivotal study are expected to enroll in the extension study, pending local regulatory approval, and one patient with POMC deficiency obesity enrolled in the pivotal study did not continue in the extension study. As of April 16, 2020, extension study data show that patients successfully maintained durable weight loss with long-term treatment with setmelanotide for a total of up to 155 weeks. Hunger scores have typically remained stable throughout the extension study. Treatment in the extension study remains ongoing. Consistent with prior clinical experience, setmelanotide has been was generally well-tolerated in the supplemental patient cohorts and in the long-term extension study.