RARE Daily

Ovid’s Experimental Angelman Therapy Fails in Phase 3 Study

December 2, 2020

Rare Daily Staff

Ovid Therapeutics said topline results from its phase 3 NEPTUNE clinical trial evaluating its experimental therapy OV101 for the treatment of the neurodevelopmental condition Angelman syndrome failed to meet the primary endpoints.

Angelman syndrome is a rare genetic condition that is characterized by a variety of signs and symptoms. Characteristic features of this condition include delayed development, intellectual disability, severe speech impairment, problems with movement and balance, seizures, sleep disorders and anxiety.

OV101 (gaboxadol) is a delta (δ)-selective GABAA receptor agonist. These receptors are thought to have a central role in tonic inhibition, a key physiological process of the brain believed to be a core pathophysiology underlying certain neurodevelopmental disorders. Ovid acquired rights to the drug in 2015 from Lundbeck, which had been developing it as an insomnia treatment, but stopped because of safety and efficacy concerns.

NEPTUNE is a randomized, double-blind, placebo-controlled, phase 3 study that enrolled and treated 97 patients diagnosed with Angelman syndrome, 4-12 years of age, and 7 patients diagnosed with Angelman syndrome ages 2-3 years for safety and pharmacokinetic evaluation only. The study was designed to assess the effects of treatment with OV101 (oral, once-daily dosing) versus placebo over 12 weeks.

The sole primary endpoint was change in overall score on the Clinical Global Impression-Improvement-Angelman syndrome (CGI-I-AS) scale. Secondary endpoints included sleep, communication, motor function, socialization, daily living skills, and behavior domains.

OV101 failed to achieve the primary endpoint of the NEPTUNE study. Patients given OV101 showed a 0.7 point improvement in CGI-I-AS over baseline while placebo showed a 0.8 point improvement in CGI-I-AS. Secondary endpoints continue to be evaluated, although initial results show no difference between OV101 and placebo.

OV101 was well-tolerated, with no significant safety issues observed. Ovid plans to complete a full analysis of the results of the NEPTUNE study and discuss these results with the U.S. Food and Drug Administration to determine next steps, if any, for the program.

The company will continue to offer study drug to patients enrolled in the open-label extension trial (ELARA) pending further analysis of the NEPTUNE study. Ovid expects to report data from the ELARA study in the first quarter of 2021.

“Other than the ongoing ELARA study, we plan to pause our OV101 program in Angelman syndrome pending a full understanding of this outcome and discussions with regulators and investigators,” said Jeremy Levin, chairman and CEO of Ovid Therapeutics. “For now, the focus of our future development efforts will concentrate on the development of our other late-stage asset, OV935, in two rare epilepsies: Dravet and Lennox-Gastaut syndromes.”

Photo: Jeremy Levin, chairman and CEO of Ovid Therapeutics

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