Zynerba CBD Gel Fails in Pivotal Fragile X Study

Rare Daily Staff

Zynerba Pharmaceuticals said top line results from the 14-week pivotal CONNECT-FX of Zygel, its cannabidiol therapy for behavioral symptoms of children and adolescents with Fragile X syndrome, failed to achieve statistical significance versus a placebo.

The primary endpoint of the study was improvement in the Social Avoidance subscale of the Aberrant Behavior Checklist – Community FXS.

Zygel also failed to demonstrate statistical significance versus placebo in the three key secondary endpoints, which were the change from baseline to the end of the treatment period in the Irritability subscale score of the ABC-CFXS, the Socially Unresponsive/Lethargic subscale score of the ABC-CFXS, and Improvement in Clinical Global Impression.

Fragile X syndrome is a rare genetic developmental disability that is the leading known cause of both inherited intellectual disability and autism spectrum disorder. It is the most common inherited intellectual disability in males and a significant cause of intellectual disability in females, and the leading genetic cause of autism spectrum disorder. The disorder negatively affects synaptic function, plasticity, and neuronal connections, and results in a spectrum of intellectual disabilities and behavioral symptoms, such as social avoidance and irritability.

A pre-planned ad hoc analysis of the most severely impacted patients in the trial, as defined by patients having at least 90 percent methylation of the impacted FMR1 gene, demonstrated that patients receiving Zygel achieved statistical significance in the primary endpoint of improvement at 12 weeks of treatment in the Social Avoidance subscale of the ABC-CFXS compared to placebo. This group comprised 80 percent of the patients enrolled in the CONNECT-FX study.

The company believes that full methylation occurs in approximately 60 percent of the overall FXS patient population. Based on this analysis, Zynerba intends to meet with the FDA regarding a regulatory path forward for Zygel.

“The results from CONNECT-FX identified a significant patient population who responded well to Zygel and may provide us with a pathway towards licensure,” said Armando Anido, Zynerba’s chairman and CEO. “We intend to discuss the results of the study with the FDA as soon as possible.”

Photo: Armando Anido, Zynerba’s chairman and CEO