Rare Disease Report

Cannabidiol Gel Improves Behaviour in Fragile X Syndrome Patients

SEPTEMBER 28, 2017
James Radke
Zynerba Pharmaceuticals, Inc. announced positive data from its Phase 2 study examining the safety and efficacy of cannabidiol gel in patients with fragile X syndrome.

The study showed that children and teens with fragile X syndrome who were given transdermal ZYN002 cannabidiol gel for 12 weeks showed a 46% improvement (P < .0001) in the total score of Anxiety, Depression, and Mood Scale (ADAMS).

Fragile X syndrome, due to a mutation in the FMR1 gene, is the most common genetic cause of autism. Patients with this rare disease exhibit autism-like symptoms including: anxiety, mood swings, attention deficit and heightened stimuli.

The disease affects about 1 in 3,600 to 4,000 males and 1 in 4,000 to 6,000 females. Since it is an X-linked genetic mutation, males tend to have more severe symptoms.
The open-label Phase 2 study involved 20 patients (aged 6 – 17 years, mean age = 10.7 years) with fragile X syndrome who were given ZYN002 for 12 weeks. In the first 6 weeks of the study, dosing began at 50 mg per day and titrated up to a possible maximum dose of 250 mg per day by week 6, where it remained until the end of the study.

The primary endpoint for the trial was the change in the total score using ADAMS from baseline to week 12. ADAMS is a 28-item scale designed to assess general anxiety, social avoidance, compulsive behavior, manic/hyperactive behavior, and depressed mood.

At the end of 12 weeks, the mean total ADAMS score was 18.1 in the 20 patients compared to 33.4 at baseline. The -14.1 change in scores was statistically significant (P < .0001).

The subscales of ADAMS were similarly impressive (see table below).

Table: ADAMS Subscales
  ADAMS subscale  Baseline  Week 12  % change  P-value
  General anxiety
  Social avoidance
  Compulsive behaviour
  Depressed mood
 < .0001

Regarding the drug’s safety, 2 patients discontinued treatment due to worsening of pre-existing eczema. Four other patients experienced an adverse event but were not considered severe. No tetrahydrocannabinol (THC) was detected in the plasma.

Of the 18 patients who completed the study, 13 enrolled in the open label extension.

In a news release, Steven Siegel, MD, PhD Professor and Chair, Psychiatry and Behavior Sciences, Keck School of Medicine of USC said: “The data from the FAB-C trial are very exciting and demonstrate that ZYN002 may have a profound effect on improving many of the most disabling symptoms of Fragile X, such as anxiety and difficult behaviors.”

“Fragile X is a challenging genetic autism spectrum disorder, with complex symptomatology that significantly impacts patients and their families. Many children with Fragile X and their families struggle with the lack of approved drugs to safely treat their symptoms. This study suggests that ZYN002 is ready for the next phase of development, and I believe that this drug holds great promise as a potential treatment for these very difficult-to-treat symptoms.”

Zynerba plans to begin a pivotal Phase 2/3 study in 2018.

Armando Anido, Chairman and Chief Executive Officer of Zynerba added: “The clinically meaningful improvements in Fragile X symptoms and the excellent tolerability seen in the FAB-C trial are compelling. These data will allow us to discuss the pathway to approval in a meeting with the FDA, which we expect to take place during the first half of 2018.”

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