CBD Gel Promising for Fragile X Syndrome, Megan Brooks, 2019

CBD Gel Promising for Fragile X Syndrome

Megan Brooks

Medscape, 2019


SAN FRANSICO — A clear transdermal cannabidiol (CBD) gel (ZYN002, Zynerba Pharmaceuticals) improved emotional and behavioral symptoms experienced by children and adolescents with fragile X syndrome in a phase 2 open-label study, the company reports.

ZYN002 met its primary endpoint, with patients demonstrating a 46% improvement in the total score on the Anxiety, Depression, and Mood Scale (ADAMS) at week 12 compared to baseline.

ZYN002 also led to meaningful improvements in all measures of the Aberrant Behavior Checklist for Fragile X (ABC-FXS), which addresses the key symptoms of fragile X syndrome, including social avoidance, temper tantrums, repetitive movements, and hyperactivity.

“These open-label findings highlight both the short- and long-term positive impact of ZYN002 on emotional and behavioral symptoms experienced by children and adolescents with fragile X syndrome,” Donna Gutterman, PharmD, of Zynerba Pharmaceuticals, told Medscape Medical News.

The results of the FAB-C study were presented here at the American Psychiatric Association (APA) 2109 annual meeting.

Transdermal Gel

Fragile X syndrome is a genetic condition caused by a mutation in the fragile X mental retardation 1 gene, located on the X chromosome. This mutation causes dysregulation of the endocannabinoid system, resulting in significant social, behavioral, and cognitive deficits.

“There is a logic to why CBD might work in kids with fragile X,” Gutterman said.

The FAB-C study evaluated the safety, tolerability, and efficacy of ZYN002, a permeation-enhanced, pharmaceutically produced CBD gel formulated for transdermal delivery. The study included 20 patients with fragile X syndrome. Most patients were male; the median age was 9 years (range, 6 to 17 years).

Treatment with ZYN002 was initiated at a dose of 50 mg daily. The dose could be titrated up to 250 mg daily during the first 6 weeks. The initial 6 weeks of therapy were followed by a maintenance dosing period, which lasted through week 12 and was followed by an extension period of up to 24 months.

The gel is rubbed on the upper arm and takes 30 to 45 seconds to dry. Eighteen of 20 patients completed the initial 6-week phase. Safety and efficacy were analyzed at week 12. Thirteen patients continued into the 24-month extension study. Only the 12-month results were reported at the APA meeting.

The study met the primary endpoint for change from baseline to week 12 in the total score of the ADAMS scale. That scale has been validated in patients with fragile X syndrome. The ADAMS score was 33.4 at baseline and 18.1 at week 12, an improvement of 45.8% (P < .0001), Gutterman reported.

The CBD gel also led to improvements in scores on the general anxiety, social avoidance, compulsive behavior, manic/hyperactive behavior, and depressed mood subscales of the ADAMS.

ADAMS Subsales Baseline Week 12 Improvement
General anxiety 10.0 4.6 54.0% (P < .0001)
Social avoidance 10.2 4.8 52.9% (P = .0002)
Compulsive behavior 2.8 1.4 50.0% (P = .0262)
Manic/hyperactive behavior 9.4 6.1 35.1% (P = .0003)
Depressed mood 2.8 2.0 28.6% (P = .1417)

Treatment with the CBD gel also led to significant improvements in social avoidance, irritability, and social unresponsiveness/lethargy on the ABC-FXS.

ZYN002 was well tolerated. No serious adverse events were reported, and there were no clinically meaningful trends in vital signs, ECG results, or laboratory findings, including liver function test results. The most common treatment-emergent adverse events were mild to moderate gastroenteritis and upper respiratory infections.

A randomized, double-blind, placebo-controlled trial to extend these findings is currently enrolling patients in Australia, New Zealand, and the United States, Gutterman said.

Compelling Mechanism

“This is an interesting study with promising results,” Alex Kolevzon, MD, professor of psychiatry and pediatrics and clinical director of the Seaver Autism Center at the Icahn School of Medicine at Mount Sinai, New York City, told Medscape Medical News.

“CBD has a compelling mechanism with relevance to fragile X syndrome. While open-label studies must be interpreted with caution, these data support the need for larger, controlled studies,” said Kolevzon.

The study was sponsored by Zynerba Pharmaceuticals. Gutterman and two coauthors are employees of the company. Kolevzon has disclosed no relevant financial relationships.

American Psychiatric Association (APA) 2019: Abstract P5-092. Presented May 20, 2019.