A first patient has been randomized in the NEPTUNE trial, which is testing oral OV101 (gaboxadol) as a potential treatment for Angelman syndrome.
OV101 is a small molecule derived from a component found in mushrooms; it works by activating a process called tonic inhibition.
Essentially, GABA receptors on neurons (nerve cells), when activated, decrease the activity of the neuron — a sort of natural ‘pump the brakes’ system that is known as tonic inhibition. In Angelman syndrome, this process is thought to be less active as it should be. As a result, the brain becomes overloaded by different stimuli, which can trigger disease-related symptoms.
OV101 is designed to activate tonic inhibition and normalize neuronal activity, ultimately easing symptoms.
A previous clinical trial (NCT03109756) demonstrated the safety of OV101 administration in a small number of people with Angelman and fragile X syndrome, which the potential therapy is also being developed to treat.
Results from the recently completed Phase 2 study (NCT02996305) — also known as the STARS trial — showed that OV101 improved sleep, behavior, and motor abilities in adolescents and adults with Angelman.
The Phase 3 NEPTUNE trial (NCT04106557) will further assess OV101’s efficacy in treating up to 65 children with Angelman, ages 2 to 12.
“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 at 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.”
In the NEPTUNE trial, children will be treated with either OV101 or a placebo (taken orally, once daily) for 12 weeks. Most study participants will be between the ages of 4 and 12; a few younger (2-3 years old) children will also be enrolled to evaluate OV101 in this age group, according to the press release. This study is currently enrolling at two U.S. sites, one in Arizona and one in Pennsylvania; more information is available here.
Its primary goal (endpoint) is the change in the overall score on the Clinical Global Impression-Improvement-Angelman syndrome (CGI-I-AS) scale — which reflects overall clinical benefit. Use of this scale is supported by Ovid, the United States Food and Drug Administration (FDA) and Germany’s Federal Institute for Drugs and Medical Devices (BfArM), the company reported.
Secondary endpoints include changes in sleep, communicative abilities, motor function, and behavior.
Children who complete the NEPTUNE trial, and those who took part in earlier studies, may have the option of rolling over into ELARA (NCT03882918), an open-label extension trial of OV101 (meaning that all are given the investigative treatment and monitored; there is no placebo).
Results from Neptune are expected in mid-2020. Both the FDA and the BfArM have stated that, if the results are positive, they could be used to support filings for regulatory approvals.
Said Amanda Moore, the chief executive officer of the Angelman Syndrome Foundation, “I am excited about the potential of OV101 to offer hope for patients and their families.”