Ovid Therapeutics Reports Positive Topline Results from Mid-Stage Trial in Fragile X Syndrome

Rare Daily Staff

Ovid Therapeutics reported positive topline results from the signal-finding phase 2 ROCKET trial of its experimental therapy OV101 in males with Fragile X syndrome, which showed that it was tolerable and safe and produced significant reductions in behavioral and functional symptoms.

Fragile X syndrome is the most common inherited form of intellectual disability and autism, with a prevalence of 1 in 3,600 to 4,000 males and 1 in 4,000 to 6,000 females in the United States. Individuals with Fragile X syndrome often have a range of behavioral challenges, such as cognitive impairment, anxiety, mood swings, hyperactivity, attention deficit, poor sleep, self-injury, and heightened sensitivity to various stimuli, such as sound. They are also prone to comorbid medical issues including seizures and sleep disturbance.

Fragile X syndrome results from mutations in the FMR1 gene, which blocks expression of the Fragile X Mental Retardation Protein (FMRP), an important protein in GABA synthesis. Extrasynaptic GABA levels are abnormally reduced, and there is also dysregulation of GABA receptors, which causes tonic inhibition: the brain becomes inundated with signals and loses the ability to separate background noise from critical information. There are no FDA-approved therapies for Fragile X syndrome, and treatment primarily consists of behavioral interventions and pharmacologic management of symptoms.

OV101 (gaboxadol) specifically targets the disruption of tonic inhibition, a central physiological process of the brain that is thought to be the underlying cause of certain neurodevelopmental disorders. The ROCKET trial was a signal-finding, randomized, double-blind, parallel-group trial to evaluate the safety, tolerability and efficacy of OV101 in males ages 13 to 22 with a confirmed diagnosis of Fragile X syndrome. The primary objective of the study was to assess the safety and tolerability of OV101 over 12 weeks of treatment in three different active dose arms. The secondary objective was to evaluate changes in behavior after 12 weeks of treatment. A total of 23 participants were randomized into the study across three active-arm dose cohorts.

OV101 met its primary objective and appeared to be well tolerated over 12 weeks of treatment with no serious adverse events reported across the three dose cohorts. OV101 also demonstrated a statistically significant effect on secondary behavioral endpoints in the three combined study groups as follows: 26.2 percent mean improvement in the Aberrant Behavior Checklist-Community for Fragile X syndrome total score from baseline to week 12; and a 21.6 percent mean improvement in the Anxiety, Depression and Mood Scale total score from baseline to week 12. Statistically significant improvements were also observed across various subscales. OV101 also demonstrated a statistically significant mean reduction of 0.4 in the Clinical Global Impressions Severity scale total score from baseline to week 12.

“Developing treatment options in Fragile X syndrome has historically been challenging, and there continues to be a high unmet medical need,” said Amit Rakhit, president and chief medical officer of Ovid Therapeutics. “This was the first interventional clinical study of OV101 in the Fragile X population, and we are encouraged by the safety profile and the positive efficacy signals we see across multiple behavior domains from this small, active-arm study. Lower and middle dosing regimens appear to be superior to the higher, three-times-daily dose, which is consistent with the emerging profile of OV101.”

Based on these results, Ovid Therapeutics believes that OV101 has the potential to represent a compelling new therapeutic option for individuals with Fragile X syndrome, and plans to request meetings with regulatory authorities to discuss the development path and registration pathway for OV101 for the treatment of Fragile X syndrome.

Ovid is also testing OV101 for the treatment of Angelman syndrome in a phase 3 clinical study. The U.S. Food and Drug Administration has granted Orphan Drug and Fast Track designations for OV101 for both the treatment of Angelman syndrome and Fragile X syndrome. The European Commission has granted orphan drug designation to OV101 for the treatment of Angelman syndrome.

Photo: Amit Rakhit, president and chief medical officer of Ovid Therapeutics