Trial Results for Zygel, CBD Gel Treatment for Fragile X, Likely by Mid-year

Top-line results from the CONNECT-FX trial testing the cannabidiol (CBD) gel Zygel as a potential treatment for behavioral symptoms in children and teenagers with fragile X syndrome are expected by late June.

Should findings be positive, Zynerba Pharmaceuticals plans to request a meeting with the U.S. Food and Drug Administration (FDA) to determine whether existing data would support a regulatory review for possible approval.

The company is planning to file a new drug application later this year, meaning an FDA decision on Zygel is possible by mid-2021, Zynerba said in a press release.

Despite the ongoing COVID-19 pandemic, Zynerba’s timeline for Zygel remains unchanged.

“In response to the pandemic, Zynerba implemented important initiatives that we believe protect the safety of patients, clinical investigators and their staff … and should allow us to conclude all three of our ongoing clinical trials and report top line results within our stated timelines,” said Armando Anido, the company’s chairman and CEO.

CBD, a compound found in the cannabis plant, is not psychoactive — that is, it does not induce a “high.” Current research seeks to understand whether CBD may modulate the endocannabinoid system, which is important for nerve cell communication and protection from damage. Emerging evidence suggests that behavioral problems in people with fragile X are linked with abnormalities in the endocannabinoid system.

Zygel delivers CBD into the bloodstream through the skin after being applied to the shoulder or upper arm.

A Phase 2/3 study, CONNECT-FX (NCT03614663) is testing its efficacy and safety in 212 children, ages 3 to 17, who are moderately to severely impacted by fragile X at sites across the U.S., Australia, and in New Zealand.

Children are being given Zygel gel or a placebo for 14 weeks. Daily doses are determined based on the individual’s weight, with two sachets — one applied every 12 hours — for those weighing 35 kg (about 77 pounds) or less, and four sachets — two every 12 hours — for those over 35 kg.

The primary efficacy assessment is the Aberrant Behavior Checklist-Community Fragile X Factor Structure (ABC-C), a caregiver-reported measure of behavior. ABC-C is used to evaluate social avoidance, irritability, hyperactivity, being socially unresponsive, stereotypies (purposeless, repetitive movements), and inappropriate speech.

Patients who complete the main trial have the opportunity to enroll in an open-label extension study (NCT03802799), where all are given Zygel for up to one year (52 weeks). As of May 8, 180 of the 188 children (96%) who finished CONNECT-FX have moved into the extension study.

Besides fragile X, Zynerba is testing Zygel in Phase 2 trials with children and adolescents with autism spectrum disorder and 22q11.2 deletion syndrome, a genetic disease that, among its many symptoms, can affect intellectual development and behavior.