Ovid cuts its losses on controversial Angelman syndrome drug, making its crushing development halt permanent
After a turbulent couple of years, Ovid is officially doing away with a program it had once championed in the face of heavy analyst skepticism.
Ovid has discontinued development of OV101, or gaboxadol, in Angelman syndrome and will not pursue further clinical trials for Fragile X syndrome, the company announced Monday morning. The news comes after Ovid had previously paused development in Angelman when the compound flunked a Phase III trial in December.
Ovid $OVID shares, which were crushed after that December readout, were more muted Monday — the stock was down about 2% in early morning trading. Ovid did not respond to a request for comment Monday morning.
In a release, the biotech said the decision to shut down OV101 was based on the “totality” of data from at least four clinical trial programs. Though the compound had demonstrated safety and tolerability, the efficacy proved lacking and ultimately prompted the discontinuation.
OV101 itself is a delta-selective GABAA receptor agonist and was one of the first candidates put into testing for the treatment of Angelman syndrome, a genetic disorder where a mutation in an enzyme in the brain can lead to a wide range of different symptoms. The gene involved is UBE3A: The mutation occurs in the uterus and affects every cell in the brain as it develops.
The big tumult over the experimental drug began back in 2018, when Ovid reported Phase II results. Though the twice-daily drug arm whiffed badly on statistical significance, CEO Jeremy Levin pushed forward with a Phase III, arguing that the true efficacy measure came in a lesser-known secondary measure of physician-rated clinical global impressions of improvement (CGI-I).
Ovid and Levin continued to insist that they nailed this endpoint, but analysts and investors saw it as a fluke that couldn’t be replicated. The skeptics eventually proved correct as OV101 again missed in its Phase III study focusing on CGI-I as the placebo group outperformed the drug arm. OV101 also whiffed on all secondary endpoints in the Phase III study.
At the time, Ovid said it would pause development of the program as it sought discussions with the FDA to “determine next steps, if any.” Not only did it mark a setback for Ovid but also for patients with Angelman syndrome, for which there remain no FDA-approved therapies.
With OV101 out of the picture, Ovid is pivoting toward its earlier-stage assets, first and foremost being OV882. A short hairpin RNA therapy targeting UBE3A gene expression in neurons, this program will continue Ovid’s efforts in Angelman syndrome, the company said Monday. It’s still in very early stages, however, having not yet hit the preclinical phase.
There’s also the OV935, or soticlestat, program for developmental and epileptic encephalopathies, which Ovid licensed to Takeda at the end of March. Ovid pulled in a $196 million upfront payment for that program, and is eligible for up to $660 million in milestones and up to 20% royalties on potential sales. The company has no further financial obligations for this program, it noted Monday.