Gaboxadol Reports Positive Topline Results in Phase 2 for Fragile X Syndrome


Data showed that Ovid Therapeutics’ gaboxadol, also known as OV101, was well-tolerated and had a significant effect on secondary behavioral end points in the 3 combined study groups.

Dr Elizabeth Berry-Kravis

Elizabeth Berry-Kravis, MD, PhD, professor of pediatrics and neurological sciences, and co-director, Molecular Diagnostics Section of the Genetic Laboratory, Rush University Medical Center

Elizabeth Berry-Kravis, MD, PhD

Ovid Therapeutics has announced positive topline results from its phase 2 ROCKET trial assessing gaboxadol (OV101) in the treatment of male patients with Fragile X syndrome, also known as Martin-Bell syndrome, an inherited form of intellectual disability and autism that has no approved treatment options.1

Data showed that over 12 weeks of treatment, the treatment appeared well-tolerated as none of the 3 patient cohorts reported serious adverse events (AEs), and the novel delta (δ)-selective GABAA receptor agonist showed a statistically significant effect on secondary behavioral end points in the 3 combined study groups.

From baseline to Week 12, there was a 26.2% improvement in Aberrant Behavior Checklist-Community for Fragile X syndrome (ABC-CFXS) total score (P = .002) and a 21.6% mean improvement in the Anxiety, Depression, and Mood Scale (ADAMS) total score (P = .004). Various subscales for both assessments were revealed to be significantly improved as well.

In addition, gaboxadol treatment was associated with a significant mean reduction of 0.4 in the Clinical Global Impressions Severity scale (CGI-S) total score (P = .002) over the 12-week study period.

“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 Elizabeth Berry-Kravis, MD, PhD, professor of pediatrics and neurological sciences, and co-director, Molecular Diagnostics Section of the Genetic Laboratory, Rush University Medical Center, in a statement. “Fragile X is a challenging neurodevelopmental genetic condition, with complex symptomatology that significantly impacts patients and their families. 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.”

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With regard to the primary endpoint of safety and tolerability, the most common AEs included diarrhea (9%), irritability (9%), headache (13%), and upper respiratory infections (18%), with the majority of AEs reported as mild in severity (94%).

ROCKET was designed to evaluate the safety, tolerability and efficacy of gaboxadol in males ages 13 to 22 with a confirmed diagnosis of Fragile X syndrome, in signal-finding, randomized, double-blind, parallel-group fashion. There were 23 participants randomized across 3 active-arm dose cohorts: 5-mg once-daily gaboxadol (QD; n = 4), 5-mg twice-daily gaboxadol (BID; n = 5), and 5-mg three-times-daily gaboxadol (TID; n = 6). The primary objective of the study was safety and tolerability, and the secondary objective was to evaluate changes in behavior after 12 weeks of treatment.

“Developing treatment options in Fragile X syndrome has historically been challenging, and there continues to be a high unmet medical need,” said Amit Rakhit, MD, MBA, president and chief medical officer, Ovid Therapeutics, in a statement. “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.”

“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,” Rakhit added.

Ovid also released data from the SKYROCKET trial, a non-drug interventional study in Fragile X syndrome, which enrolled 13 males ages 8 to 29 years (mean, 17) with a confirmed diagnosis of Fragile X syndrome. The primary objective was to evaluate the suitability and reliability of different scales for the assessment of behavior, sleep, and functioning and also to determine which tools would be the most appropriate for future interventional clinical efficacy trials of individuals with Fragile X syndrome. Ovid noted that the “data will help inform future study design, including potential endpoints and measures to mitigate placebo response.”

By mid-2020, Ovid Therapeutics is also expected to report topline data from its phase 3 pivotal trial of gaboxadol for the treatment of Angelman syndrome (AS). The NEPTUNE trial (NCT04106557) comes on the heels of a phase 2 study that showed overall improvement in patients treated with the therapy, a feat achieved for the first time in 50 years.2,3

To help address the lack valuable and effective measurements to use in clinical trials for Fragile X, Ovid Therapeutics assessed what been done in previous trials of Fragile X syndrome to establish a Visual Analog Scale, incorporating behavior, cognition, speech and communication, sensory perception, emotions, social, activities of daily living (ADL), and notably, caregiver impacts. To find out more about this scale and what prompted the incorporation of patient and caregiver centered facets into it, NeurologyLive spoke with Rakhit, at the 2019 American Academy of Neurology (AAN) Annual Meeting in Philadelphia, Pennsylvania. Watch him provide his insight below.


1. Ovid Therapeutics Announces Positive Topline Results from the Phase 2 ROCKET Trial of OV101 for the Treatment of Fragile X Syndrome [press release]. New York, NY: Ovid Therapeutics; Published May 7, 2020. Accessed May 7, 2020.

2. Ovid Therapeutics announces first patient randomized in pivotal phase 3 NEPTUNE trial of OV101 for the treatment of Angelman syndrome [press release]. New York, NY: Ovid Therapeutics; September 12, 2019. Accessed January 15, 2020.

3. Bird LM, Ochoa-Lubinoff C, Tan WH, et al. STARS: results from a safety and efficacy study of OV101 (gaboxadol) in adults and adolescents with Angelman syndrome. Presented at: 2019 American Academy of Neurology Annual Meeting; May 4-10, 2019; Philadelphia, PA.

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