OV101 Fails to Meet NEPTUNE Trial Goals; Ovid Will Suspend Development

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by Steve Bryson, PhD |

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OV101 (gaboxadol), designed to improve motor skills, cognition, and memory in people with Angelman syndrome, did not meet its primary goal (endpoint) in Ovid Therapeutics’ Phase 3 NEPTUNE clinical trial, according to top-line results. The trial had tested the therapy in children and adolescents.

Ovid now plans to suspend its OV101 program, which was developing the therapy for both Angelman and fragile X syndrome, while the company meets with its researchers and regulators.

“We will fully assess all the data from this trial to understand this outcome and determine next steps, if any, for OV101 in this and other conditions, including Fragile X syndrome,” Amit Rakhit MD, Ovid’s president and chief medical officer, said in a press release.

The sole primary endpoint in NEPTUNE (NCT04106557) was a change in participants’ overall scores on the Clinical Global Impression Improvement Angelman syndrome (CGI-I-AS) scale, a seven-point scale that assesses changes in a patient’s condition across five key areas, specifically communication, fine and gross motor skills, behavior, and sleep.

The results showed a 0.7 point improvement among participants who received OV101 compared with 0.8 points in those given a placebo, Ovid reported. 

While secondary endpoints continue to be assessed, the initial results showed no significant impact of OV101 over a placebo. 

Pending an analysis of NEPTUNE’s data, and discussions with the U.S. Food and Drug Administration (FDA), the company will continue to offer OV101 to patients enrolled in ELARA (NCT03882918) — an open-label extension trial with results expected in the first quarter of 2021. 

“We are deeply disappointed with the outcome of the NEPTUNE trial, which did not achieve its primary endpoint,” said Jeremy Levin, PhD, Ovid’s chairman and CEO. “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.”

Along with Angelman syndrome, Ovid had been developing OV101 to treat fragile X, another condition characterized by reduced tonic inhibition — a mechanism that decreases excessive nerve cell activity in the brain.

OV101 is thought to ease symptoms by normalizing tonic inhibition via the activation of specific receptors on the surface of nerve cells that bind the signaling molecule, or neurotransmitter, GABA (gamma-aminobutyric acid). By activating these receptors, OV101 is thought to increase tonic inhibition and, consequently, ease the symptoms of these syndromes. 

The therapy was found to be safe and well-tolerated in a Phase 1 trial (NCT03109756), and to lead to improved sleep, motor function, and communication skills, as well as reduced anxiety, in the Phase 2 STARS trial (NCT02996305). 

A global, placebo-controlled, Phase 3 study, NEPTUNE enrolled 97 children and adolescents, ages 4-12 and diagnosed with Angelman syndrome. Children ages 2-3 also were included for safety assessment. Participants were given oral OV101 or a placebo, taken once daily over 12 weeks.

The FDA had granted OV101 orphan drug status in September 2016 to treat Angelman syndrome, and had extended that designation to fragile X  in October 2017. OV101 was further granted the FDA’s rare pediatric disease designation for Angelman in June 2020.

“NEPTUNE is our first study focused on the pediatric and adolescent population in Angelman syndrome,” Rakhit said.  

“We are sincerely grateful for the commitment and dedication of patients, families, investigators, and employees to this program, and in particular, to those who participated in the NEPTUNE trial,” he added.