Rare Daily Staff

Zynerba Pharmaceuticals reported positive top line results from the exploratory, open label phase 2 INSPIRE trial of its transdermal CBD gel Zygel on behavioral and emotional symptoms of 22q11.2 deletion syndrome.

The company said based on the positive results it will request a meeting with the U.S. Food and Drug Administration to discuss the data and the regulatory path forward.

22q is caused by a small missing piece of the 22nd chromosome. The deletion occurs near the middle of the chromosome at a location designated q11.2. It is considered a mid-line condition, with physical symptoms including characteristic palate abnormalities, heart defects, immune dysfunction, and esophageal/GI issues, as well as debilitating neuropsychiatric and behavioral challenges. Anxiety is among the most common neuropsychiatric symptoms of 22q and researchers have found that for children with 22q, anxiety is linked to poorer adaptive behaviors such as self-care and communication skills that affect daily life. Children with 22q also experience withdrawn behavior, ADHD, cognitive impairment, and autism spectrum disorder that affect communication and social interaction. Later in life, they are at an increased risk of developing mental illnesses such as schizophrenia.

Zygel is the first and only pharmaceutically-manufactured cannabidiol formulated as a patent-protected permeation-enhanced clear gel, designed to provide controlled drug delivery into the bloodstream transdermally. Recent studies suggest that cannabidiol may modulate the endocannabinoid system and improve certain behavioral symptoms associated with neuropsychiatric conditions. Zygel is an experimental drug in development for the potential treatment of behavioral symptoms associated with Fragile X syndrome (FXS), 22q11.2 (22q) deletion syndrome, and autism spectrum disorder (ASD).

The company has received orphan drug designation for cannabidiol, the active ingredient in Zygel, from the FDA and the European Commission for the treatment of FXS and by the FDA for the treatment of 22q. Additionally, Zygel has been designated a Fast Track development program for treatment of behavioral symptoms of FXS.

The phase 2 trial was designed for signal detection by assessing the safety, tolerability, and efficacy of Zygel for the treatment of behavioral symptoms of 22q in children and adolescents. Zygel was administered to patients with 22q as add-on therapy to their standard of care and utilized a variety of efficacy assessments. Key findings from the trial disclosed today include:

The total score and all five subscales of the Anxiety, Depression and Mood Scale (ADAMS) showed statistically significant improvements at 14 weeks of treatment compared to baseline. All five subscales of the Aberrant Behavior Checklist – Community (ABC-C) showed statistically significant improvements at 14 weeks of treatment compared to baseline.

The Pediatric Anxiety Rating Scale (PARS – R) showed statistically significant improvements at 14 weeks of treatment compared to baseline. The majority of patients showed clinically meaningful improvements at week 14 as demonstrated by the Clinical Global Impression – Improvement (CGI-I). Seventy-five percent of patients were rated by the clinicians as “improved,” “much improved,” or “very much improved” with nearly two-thirds (62.5 percent) of the patients being “much improved” or “very much improved.”

“We believe the data from this phase 2 trial are very encouraging and reinforce the potential of Zygel for the treatment of behavioral symptoms in children and adolescents with 22q, and we look forward to discussing the regulatory path forward with the FDA with these data in hand,” said Armando Anido, chairman and CEO of Zynerba. “In the near term, we will focus our resources on completing the RECONNECT trial for children and adolescents with Fragile X syndrome and progressing 22q.”

Photo: Armando Anido, chairman and CEO of Zynerba

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