Zynerba Pharmaceuticals Inc (NASDAQ:ZYNE) has received guidance from the US Food and Drug Administration (FDA) on a confirmatory Phase 3 trial of Zygel in patients with Fragile X syndrome (FXS).
The trial, which will be called RECONNECT (A Randomized, Double-Blind, Placebo-Controlled, Multiple-Center, Efficacy and Safety Study of ZYN002 Administered as a Transdermal Gel to Children and Adolescents with Fragile X Syndrome), is designed to evaluate the efficacy and safety of Zygel in children and adolescents with FXS.
Zynerba said the study is planned to confirm the positive results observed in a population of responders in its CONNECT-FX trial, a randomized, double-blind, placebo-controlled trial that assessed the efficacy and safety of Zygel as a treatment for the behavioral symptoms of FXS previously conducted by the company.
READ: Zynerba Pharmaceuticals says it is fully funded into 2024; lays out plans to advance four Zygel indications in 4Q results
The company said it believes that the results, if positive, from RECONNECT will be sufficient to support the submission of a New Drug Application for Zygel in patients with FXS.
“Following productive discussions and alignment with the FDA, we believe we have a clear path forward for Zygel in Fragile X syndrome. We are excited to advance Zygel into the RECONNECT trial, a pivotal, multi-national, confirmatory Phase 3 trial in patients with FXS in the third quarter of 2021,” said CEO Armando Anido in a statement.
“If the results are positive, Zygel could become the first FDA approved treatment option for the significant unmet medical need that affects patients with FXS and their families.”
The RECONNECT trial will be an 18-week trial that will enroll approximately 200 children and adolescents of which approximately 160 patients will have complete (100%) methylation of their FMR1 gene and approximately 40 patients will have partial methylation of their FMR1 gene.
The primary endpoint for the trial will be the change in the Aberrant Behavior Checklist-Community FXS Specific Social Avoidance (ABC-C) subscale in patients who have complete methylation of their FMR1 gene. All patients, including the cohort of partially methylated patients, will be included in a key secondary endpoint analysis.
The company performed an analysis of the CONNECT-FX population within those patients having complete methylation of their FMR1 gene (n = 137 of 212 in the intent to treat population) to evaluate the effect of Zygel versus placebo. One patient did not have a post-baseline efficacy measure and was therefore not included in the efficacy analysis.
Baseline demographics for patients with complete methylation of the FMR1 gene are shown below. The group is similar to the previously reported full data set of patients and the cohort of patients with ≥90% methylation. The majority of patients were male and the children had a mean age of 9 to 10 years old.
“The treatment difference versus placebo and p value on the primary endpoint of improvement in the ABC-C Social Avoidance subscale in patients with complete methylation are consistent with the previously reported findings in patients with at least 90% methylation, despite the fact that the study was not powered to evaluate either of these patient populations,” said Dr Joseph Palumbo, chief medical officer at Zynerba.
“We believe the CONNECT-FX trial was instrumental in advancing our understanding of the science of Fragile X Syndrome. We look forward to leveraging what we learned as we seek to confirm our findings in the RECONNECT trial.”
Contact the author: patrick@proactiveinvestors.com
Follow him on Twitter @PatrickMGraham