- In its quest in finding the first-ever treatment for Angelman syndrome, Ovid Therapeutics released mixed topline data on Monday from a Phase 2 clinical trial for the company's top drug, OV101.
- While the drug achieved its primary endpoint on safety, results on efficacy were more ambiguous. One metric showed statistical improvement versus a placebo when pooling the once-daily and twice-daily treatment groups, but the drug failed to record a significant edge in other areas testing behavior, sleep and gait.
- As Ovid's only Phase 2 drug, OV101 is Ovid's most advanced drug in its pipeline. Investors responded negatively to the data, sending shares in the company down 31% by value on Monday morning.
The clinical trial was the first of its kind in studying Angelman syndrome, a rare genetic disorder affecting roughly one in 15,000 Americans. Never before has a company sponsored a double-blind, placebo-controlled clinical trial for the disorder.
Angelman syndrome severely impairs behavior, learning, verbal communication, motor skills and sleep. The Food and Drug Administration has no approved medicines or established treatments and granted Fast Track and Orphan Drug designations to OV101.
OV101 is an oral medication targeting extrasynaptic GABA receptors, working off the theory that Angelman syndrome could be caused from an excessive number of GABA transporters, which leads to a deficiency of the GABA chemical in the brain. It's the first investigational drug to specifically target the disruption of tonic inhibition.
The Phase 2 trial, named STARS, divided 88 patients into three treatment groups: once-daily, twice-daily and placebo dosing. Physicians analyzed the patients after 12 weeks at the 13 trial sites located in the U.S. and Israel.
Ron Thibert, chair of the trial's steering committee, characterized the initial data as "encouraging" in a statement.
"The data reported today are the first data in Angelman syndrome to show a compound specifically targeting the syndrome having a clinical effect," said Thibert, who is also director of the Angelman Syndrome Clinic at Mass General Hospital. "Based on these data, I believe OV101 has the potential to offer a clinically meaningful benefit specific to people living with Angelman syndrome."
The primary endpoint was simply testing for the drug's safety. The study achieved that goal with statistical significance.
Secondary endpoints, of which there were 17, focused on efficacy in various measures.
The company said the drug showed measured improvement in clinical global impressions of improvement (CGI-I), a metric that allows physicians to take into consideration a variety of clinical symptoms. For CGI-I, 67% of patients saw some form of improvement with a dosage compared to 39% from the placebo.
However, when the treatment groups are divided between the once-daily and twice-daily doses, only the once-daily group met statistical significance — suggesting the drug's effects are not conventionally dose-dependent.
Ovid plans to discuss the drug's registrational pathway with the FDA going forward. Additionally, the company said it will launch an open-label, one-year extension study for those involved with previous OV101 studies with Angelman syndrome, aiming to start that trial later this year.
OV101 testing for Fragile X syndrome, the most common inherited form of intellectual disability and autism, continues to progress forward as well. Last month, Ovid began Phase 2 testing against that disorder for young males aged 13 to 22.