OV101 Well-tolerated, Effective in Fragile X Patients, Phase 2 Trial Shows

Treatment with OV101 (gaboxadol) was well-tolerated and significantly eased behavioral and functional symptoms in people with fragile X syndrome, top-line data from a Phase 2 clinical trial show.

The results support the development of OV101, and the company plans to discuss next steps with regulatory agencies, ultimately seeking to obtain approval for OV101 in treating fragile X, Ovid Therapeutics said in a press release.

OV101 is designed to activate GABA_A receptor activity to restore tonic inhibition — the brain’s ability to distinguish between inhibitory and excitatory signals — in patients with fragile X and Angelman syndrome.

The ROCKET Phase 2 trial (NCT03697161) evaluated the safety and effectiveness of OV101 in 23 males with fragile X, ages 13 to 22. A 5 mg dose of OV101 was administered orally to participants once, twice, or three times per day for 12 weeks.

No severe adverse reactions to treatment were found in any group. The most common side effects included diarrhea (9%), irritability (9%), headache (13%), and upper respiratory infections (18%). Most side effects were mild in severity (94%).

“I am encouraged by the safety results of this Phase 2 study of OV101 and am excited to further investigate its therapeutic potential in patients living with Fragile X syndrome,” said Elizabeth Berry-Kravis, MD, PhD, a professor of pediatrics and neurological sciences at Rush University Medical Center, Chicago, Illinois.

To evaluate effectiveness, the researchers relied on several validated scales that assess clinical well-being. Those included the Aberrant Behavior Checklist-Community (ABC-C) adapted for fragile X, the Anxiety, Depression and Mood Scale (ADAMS), and the Clinical Global Impressions-Severity and -Improvement scales (CGI-I and CGI-S).

Across all measures, patients showed significant improvements after the 12-week treatment when compared to initial scores. At week 12, the ABC-C scale showed a 26.2% mean improvement, while the ADAMS tool showed a 21.6% mean benefit. Significant improvements (lower scores) also were seen across various subscales of social withdrawal, hyperactivity, stereotypic (repetitive, purposeless) behavior, irritability, and anxiety.

In addition, OV101 led to a statistically significant mean reduction of 0.4 points in the CGI-S score. Communication, anxiety and activities of daily living were among the domains with meaningful benefits.

“The data from the ROCKET trial demonstrate that OV101 may have a meaningful effect on improving the lives of some individuals living with Fragile X syndrome,” said Berry-Kravis.

Amit Rakhit, MD, president and chief medical officer of Ovid, added: “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.”

Results showed that those taking OV101 once or twice daily had a greater improvement compared to the highest dosage group. Yet, further analysis is needed before determining a recommended dose for future investigations.

“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,” said Rakhit. “We are in the process of further evaluating which specific dose to advance in future studies, and we look forward to moving this program forward to discussions with regulators to determine next steps for the development of OV101 in the Fragile X indication.”

Ovid also has shared preliminary data from another trial, called SKYROCKET, which was conducted in parallel with ROCKET to evaluate the scales used to assess behavior, sleep and functioning in 13 males with fragile X (ages 8 to 29). No treatment was tested.

Researchers found significantly more variability in results reported by caregivers (ABC-C and ADAMS) than by clinicians (CGI-I and CGI-S). Findings from this study ultimately will help design clinical trials testing the benefits of potential therapies.