American Academy of Neurology

ZYN002 for Fragile X Syndrome: Gel Safely Reduces Irritability in Children

Jessica Nye, PhD
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Publish Date
AAN 2025 San Diego
Credit: Getty Images
Researchers sought to assess the long-term safety and efficacy of ZYN002 for the treatment of behavioral symptoms associated with fragile x syndrome (FXS).
A total of 73.3% of patients who stayed on ZYN002 and 72.0% of those who switched from placebo showed a meaningful improvement in CaGI-C scores at 36 months.

The topical treatment ZYN002 is safe and associated with a clinically-meaningful reduction in irritability-related behavioral symptoms among children and adolescent patients with fragile X syndrome (FXS), according to study results presented at the 2025 American Academy of Neurology (AAN) annual meeting, held from April 5 to 9, 2025, in San Diego, California.

ZYN002 is a pharmaceutically-produced cannabidiol formulated as a topical gel for transdermal delivery. ZYN002 is not derived from plants.

In the analysis, researchers included children and adolescents (N=240) with FXS aged 3 to 17 years who entered the open-label extension (OLE) trial after participating in CONNECT-FX (ZYN2-CL-016; ClinicalTrials.gov Identifier: NCT03614663), a phase 3, double-blind, placebo-controlled trial, or FAB-C (ZYN2-CL-009), a phase 1/2, open-label trial.

The primary outcomes were the rate of adverse events (AEs) and changes in vital signs, laboratory outcomes, and electrocardiogram parameters.

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Secondary results support further study of ZYN002 in patients with FXS.

The secondary outcomes were the changes in FXS-specific Aberrant Behavior Checklist-Community (ABC-CFXS) scores and Caregiver Global Impression of Change (CaGI-C) irritable and disruptive behavior scores.

Throughout the OLE, ZYN002 was found to be well-tolerated and associated with a favorable safety profile. The most common AE was application site pain (6.7%).

At the time of entry in the OLE study, a subset of patients (n=197) exhibited a clinically meaningful improvement in ABC-CFXS irritability scores from CONNECT-FX baseline. In this subset, a clinically meaningful improvement in CaGI-C scores was observed at month 36 of the OLE among 73.3% of patients who remained on ZYN002 and among 72.0% of patients who switched from placebo.

This analysis may have been limited by pooling data from double-blind and open-label trials.

“ZYN002 has a favorable safety profile and is generally well tolerated. Secondary results support further study of ZYN002 in patients with FXS,” the researchers concluded.

Disclosure: This research was supported by Harmony Biosciences. Please see the original reference for a full list of disclosures

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References:

Bzdek K, Thibodeau A, Tich N, et al. Long-term safety and effectiveness of ZYN002 cannabidiol transdermal gel in the treatment of irritability-related behavioral symptoms in children and adolescents with fragile X syndrome: update to open-label extension study (ZYN2-CL-017). Abstract presented at: 2025 AAN Annual Meeting; April 5-9, 2025; San Diego, CA. Abstract S31.007.