Objective: To assess the long-term safety and effectiveness of ZYN002, a pharmaceutically produced transdermal cannabidiol gel in development for Fragile X syndrome (FXS).

Background: ZYN002 is a pharmaceutically produced (not plant-derived) cannabidiol that has been uniquely formulated as a gel for transdermal delivery and is currently under investigation for the treatment of behavioral symptoms associated with Fragile X Syndrome (FXS). ZYN2-CL-017 is an ongoing, long-term open-label safety extension (OLE) trial of ZYN002 in patients with FXS.

Design/methods: Patients entered the OLE trial from CONNECT-FX (ZYN2-CL-016, NCT03614663), a phase 3, double-blind placebo-controlled trial, and FAB-C (ZYN2-CL-009) a phase 1/2, open-label trial. Data analyses are reported on data through January 31, 2024. Safety assessments included adverse events (AEs), vital signs, labs, and electrocardiograms (ECGs). Secondary analysis assessments included the Irritability subscale of the FXS-specific version of the Aberrant Behavior Checklist-Community (ABC-C_FXS), an observer-reported outcome, and caregiver global impression of change (CaGI-C) in irritable and disruptive behaviors.

Results: A total of 240 patients aged 3-17 at the time of entry into the OLE have been included in this analysis. ZYN002 was generally well tolerated with a favorable safety profile. The most common treatment-related AE was application site pain (6.7%). In secondary analysis cohort (n=197), patients who completed CONNECT-FX and entered the OLE demonstrated clinically meaningful changes in ABC-C_FXS Irritability scores from their respective baseline values at entry into CONNECT-FX. At OLE month 36, CaGI-C scores showed clinically meaningful changes in 73.3% of patients who continued on ZYN002 and 72.0% in patients who transitioned from placebo to ZYN002 upon entry into the OLE as reported by caregivers.

Conclusions: ZYN002 has a favorable safety profile and is generally well tolerated. Secondary results support further study of ZYN002 in patients with FXS. Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.

Disclosure: Dr. Bzdek has received personal compensation for serving as an employee of Harmony Biosciences. Dr. Bzdek has stock in Harmony Biosciences. Mr. Thibodeau has received personal compensation for serving as an employee of Harmony Biosciences. Dr. Tich has received personal compensation for serving as an employee of Harmony Biosciences. Dr. Tich has stock in Harmony Biosciences. Dr. Albers has received personal compensation for serving as an employee of Harmony Biosciences. Dr. Albers has stock in Harmony Biosciences. Dr. Nomikos has received personal compensation for serving as an employee of Harmony Biosciences.