Ovid Therapeutics says Phase 2 STARS Trial of OV101 achieved primary endpoint
Ovid Therapeutic announced that the Phase 2 STARS trial of OV101 achieved its primary endpoint of safety and tolerability. The investigational medicine showed a favorable safety profile and was well tolerated in adults and adolescents with Angelman syndrome. OV101 is the only selective extrasynaptic GABAA receptor agonist in development shown to mediate tonic inhibition, a key underlying pathophysiological mechanism of Angelman syndrome. The Phase 2 STARS international study is the first industry-sponsored, randomized, double-blind, placebo-controlled clinical trial for Angelman syndrome. The study randomized 88 patients across three groups: a once-daily or twice-daily dose of OV101, or placebo. At the prespecified efficacy analysis at 12 weeks of treatment, OV101 showed a statistically significant improvement compared to placebo in the physician-rated clinical global impressions of improvement - a measure commonly used in clinical trials that allows the physician to capture a constellation of clinical symptoms. CGI-I was ranked first in the topline statistical plan. Subsequent analyses in the hierarchy were conducted on a prespecified subset of scales across the domains of behavior, sleep and gait. While the analysis of these prespecified subsets did not show a statistically significant difference from placebo, full data analyses on these domains are ongoing and will be communicated in the future. Ovid intends to discuss these data with regulatory authorities to determine the next steps for a registrational pathway. Based on these data, the company plans to initiate in the fourth quarter of 2018 an open-label extension study; Angelman syndrome patients who completed any prior OV101 study may be eligible to receive the investigational medicine in this study. STARS was a 12-week, double-blind, placebo-controlled Phase 2 study. Eighty-eight patients aged 13 to 49 years of age diagnosed with Angelman syndrome were randomized at 13 clinical trial sites in the U.S. and Israel. The study randomized patients to one of three arms: once-daily dose of OV101 at night, twice-daily dose of OV101, and placebo. The intent to treat population was 88 patients. A modified intent to treat analysis of 87 patients, which includes any patient who enrolled in the study and received at least one dose of study drug, was performed to evaluate the efficacy endpoints. The primary endpoint of the trial was to assess the safety and tolerability of OV101 compared to placebo. The STARS trial explored the clinical utility of OV101 on improvements in clinical global impressions, maladaptive behavior, sleep, and gross and fine motor skills. The study met its primary endpoint of safety and tolerability given that the adverse events with OV101 treatment were similar to placebo treatment, with the majority of AEs being mild. OV101 showed a favorable risk profile and was well tolerated through 12 weeks of treatment. Overall, the data are consistent with the favorable risk profile observed in previous insomnia trials with this investigational medicine. The most common AEs reported in the trial were vomiting, somnolence, irritability, aggression, and pyrexia. Events occurring in greater than 5 percent compared to placebo in either treatment arm included pyrexia, rash, seizure, enuresis and myoclonic epilepsy. Serious adverse events of seizure were reported in two patients: one patient in the QD dose experienced a seizure and that was deemed unrelated to study drug; one patient experienced a seizure in the BID dose group and that was assessed as possibly related to study drug by the investigator. Treatment discontinuations due to adverse events were low. One patient in the placebo arm discontinued compared to no patients and three patients in the once-daily dose group and twice-daily dose group, respectively.