Ovid Therapeutics Inc. has announced that the phase 2 STARS trial, which evaluated OV101 (gaboxadol) for the treatment of Angelman syndrome, achieved its primary endpoint of safety and tolerability.
The delta (δ)-selective GABAA
receptor agonist exhibited a favorable safety profile and proved to be well tolerated in adults and adolescents with Angelman syndrome. Consequently, plans for a registrational pathway and open-label extension study are in discussion.
“The STARS study was designed to provide information to allow us to progress the development of OV101,” said Amit Rakhit, MD, MBA, chief medical and portfolio management officer of Ovid Therapeutics, in a recent statement
. “With these findings, we have advanced our understanding of relevant endpoints to evaluate key symptoms of Angelman syndrome. Furthermore, we demonstrated that a once-daily dose of OV101 could be sufficient to drive clinically meaningful benefit to patients. We look forward to discussing the data with regulatory authorities to inform our future development plans.”
A randomized, double-blind, placebo-controlled clinical trial for Angelman syndrome, the phase 2 STARS trial
included 88 patients (adults, n=66; adolescents, n=22) ranging in age from 13 years to 49 years in the United States and Israel. The participants were randomized into 3 treatment groups: those receiving a once-daily (QD) 15 mg dose of OV101 at night, a twice-daily (BID) dose of OV101 with 10mg in the morning and 15mg at night, or placebo.
At 12 weeks of treatment at the prespecified efficacy analysis, the combined OV101 treatment arms displayed a statistically significant improvement (p=0.0206; Fisher’s Exact test) compared with placebo in the first prespecified efficacy endpoint in regards to the physician-rated clinical global impressions of improvement (CGI-I), which was ranked first in the topline statistical plan. Investigators report that this reflects an improvement in two-thirds of the participants in the combined treatment groups compared with just one-third in the placebo group.
Furthermore, the difference in CGI-I mean score at 12 weeks was statistically significant (p=0.0006) in the once-daily OV101 group compared with placebo and also in the combined OV101 treatment group versus placebo (p=0.0103) in the prespecified analysis, which used the rigorous Mixed Model Repeated Measures (MMRM) that evaluated each OV101 treatment arm independently against placebo. Furthermore, the data yielded from a post-hoc analysis who were “much” or “minimally” improved, having a CGI-I score of ≤3 suggest that younger patients who were administered a QD dose had the greatest response to OV101 compared with older age groups.
Given that the adverse events (AEs) with OV101 treatment were similar to placebo treatment, with the majority of AEs being mild, the study met its primary endpoint of safety and tolerability. Vomiting, somnolence, irritability, aggression, and pyrexia were the most commonly reported AEs with OV101 treatment. Compared with placebo, events occurring in greater than 5% (2 or more patients) in either of the OV101 treatment arms included pyrexia, rash, seizure, enuresis, and myoclonic epilepsy.
In 2 patients, serious adverse events (SAEs) of seizure were reported. In the QD dose, 1 patient experienced a seizure that was deemed unrelated to the study drug; however, another seizure experienced by a patient in the BID dose group was deemed to be potentially related to the study drug by the investigator.
Treatment discontinuations due to AEs were low though. Three patients in the BID arm and 1 patient in the placebo arm discontinued treatment; however, none of the patients in the QD dose arm discontinued. The patient in the placebo arm discontinued due to irritability. As for the 3 patients who discontinued treatment in the BID arm, 1 was due to myoclonus, 1 due to seizure, and another due to irritability/anxiety/sleep disorder. In previous insomnia trials with OV101, this data, overall, parallels with the favorable risk profile previously observed.
With this data, Ovid plans to consult with regulatory authorities in order to determine the next steps for a registrational pathway and initiate an open-label extension study (named ELARA) in the fourth quarter of 2018. ELARA will be intended for patients with Angelman syndrome who completed any prior OV101 study; this met criteria may make them eligible to receive the investigational medicine in this study.
Full clinical data from the STARS study will be presented at an upcoming medical meeting.