Ovid Therapeutics has posted a batch of topline data out of its midstage STARS trial in Angelman syndrome as it seeks out a path to approval.
The study was focused on safety and tolerability, and saw OV101 hit its primary endpoint in several of these markers, although it failed to beat out placebo in a series of subsets.
The phase 2 trial was set up with 88 patients randomized across three groups: a once-daily or twice-daily dose of OV101 or placebo.
The biotech says that at 12 weeks of treatment, OV101 “showed a statistically significant improvement compared to placebo in the physician-rated clinical global impressions of improvement (CGI-I).”
Specifically, it showed a statistically significant difference (p = 0.0206; Fisher’s exact test) between the combined OV101 treatment arms and placebo. “This reflects an improvement in two-thirds of the combined treatment groups versus one-third in placebo,” the startup explained.
This is a measure commonly used in a test geared to help doctors capture a series of clinical symptoms, and Ovid says that CGI-I was “ranked first in the topline statistical plan.”
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Overall, Ovid says that the study met its primary endpoint of safety and tolerability given that the adverse events (AEs) with OV101 treatment were similar to placebo. The most common AEs reported in the trial were vomiting, somnolence, irritability, aggression, and pyrexia.
In addition, “subsequent analyses in the hierarchy were conducted on a prespecified subset of scales across the domains of behavior, sleep and gait.”
But the company says that the analysis of these prespecified subsets “did not show a statistically significant difference from placebo,” adding that full data analyses on these domains “are ongoing,” and they’ll get back to us on what they find in the future.
The drug is seeking to treat Angelman syndrome, a rare genetic disorder that can cause delayed development, seizures, sleep problems and other medical issues. OV101 is a selective extrasynaptic GABAA receptor agonist in development that can mediate tonic inhibition, a key underlying pathophysiological mechanism of Angelman syndrome.
This medication, from Lundbeck and Merck, was put on the scrap heap nearly a decade ago, after the pair failed to get it through the clinic for insomnia. Ovid is hoping the new test and insights will reveal the hidden value of this once-failed drug.
On the back of the STARS data, Ovid now says it “intends to discuss these data with regulatory authorities to determine the next steps for a registrational pathway” and plots to start an open-label extension study (named ELARA) in the fourth quarter.
“We are excited by these data, as this is the first demonstration of positive clinical effect on overall symptomology in Angelman syndrome,” said Jeremy Levin, D.Phil., MB, BChir, chairman and chief executive of Ovid. “In collaboration with the Angelman community, we designed a robust study to evaluate prespecified endpoints that may pave the way for a registrational pathway for a disorder that has no previously approved medicines. These data are a tribute to the patients and their families and we thank them.”
“These initial data from the STARS study are encouraging, particularly the statistically significant improvement in overall symptoms that we see in the CGI-I scale in the once-daily dosing group,” said Ron Thibert, D.O., MsPH, chairperson of the STARS clinical trial steering committee, director of the Angelman syndrome clinic at Mass General Hospital for Children, and an assistant professor at Harvard Medical School. “Angelman syndrome is a complex disorder and the CGI-I scale captures the totality of global neurological deficits and helps to define the impact of medicines on the individual and their families.
“The data reported today are the first data in Angelman syndrome to show a compound specifically targeting the syndrome having a clinical effect. Ovid is the first company to have conducted a double-blind, placebo-controlled study in Angelman syndrome, providing important clinical and scientific data. Based on these data, I believe OV101 has the potential to offer a clinically meaningful benefit specific to people living with Angelman syndrome.”
Investors weren’t feeling great about the mixed data, sending the biotech’s shares down 30% in early trading.