First Participant Enrolled in Phase 3 Trial of Gaboxadol for Angelman Syndrome

The first participant has been enrolled and randomly assigned to a trial arm in the phase 3 NEPTUNE trial (NCT02996305) of gaboxadol (OV101; Ovid Therapeutics, New York, NY) for Angelman syndrome (AS).

Approximately 60 children age 4 to 12 years of age with Angelman syndrome are planned to be enrolled and randomly assigned to receive gaboxadol or placebo. A limited number of children age 2 to 3 years will also be enrolled to evaluate pharmacokinetics, safety, and tolerability in a younger age group.

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

 “There are currently no other therapies in clinical development for Angelman syndrome and no approved treatments for this disorder exist today,” said Amit Rakhit, MD, MBA, chief medical officer and head of research and development, Ovid. “We believe the first patient randomized in the pivotal Phase 3 NEPTUNE trial is a major step toward establishing the clinical effectiveness of OV101 in Angelman syndrome and one that we hope will result in the first approved medicine for individuals living with this rare neurologic condition.” 

The most common cause of AS is a loss-of-function mutation in ubiquitin protein ligase E3A (UBE3A); AS is also associated with reduction in tonic inhibition that occurs at the delta (δ)-selective GABAA receptor. Gaboxadol is a novel delta (δ)-selective GABAA receptor agonist.A rare genetic disorder, AS is characterized by delayed development, intellectual disability, severe speech impairment, problems with movement and balance, seizures, sleep disorders, and anxiety. 

In laboratory studies and animal models, gaboxadol selectively activated the δ-subunit of GABAA receptors in the extrasynaptic space, thereby impacting neuronal activity through tonic inhibition. In preclinical studies, it was observed that gaboxadol improved symptoms of Angelman syndrome and Fragile X syndrome.