Cannabidiol (CBD) has recently been lauded for its many uses, ranging from stress relief to seizure reductions. Specialty pharmaceuticals company Zynerba Pharmaceuticals (“Zynerba”) developed an experimental cannabidiol gel called Zygel for patients with Fragile X syndrome (FXS). According to Fragile X News Today, data from the Phase 2/3 CONNECT-FX clinical trial’s open-label extension highlighted the sustained tolerability of Zygel over time.
Fragile X Syndrome (FXS)
FMR1 gene mutations on the X chromosome cause Fragile X syndrome (FXS), a rare genetic disorder characterized by developmental and intellectual disability. Normally, the FMR1 gene encodes for the production of fragile X mental retardation 1 protein; this protein plays a role in nervous system health and function. However, the gene mutations halt this production, causing protein deficiencies and related health effects. While FXS can affect both males and females, males usually have more severe symptoms. Symptoms and characteristics associated with FXS include:
- Developmental delays and missing developmental milestones
- Learning or intellectual disabilities
- Anxiety, depression, or hyperactivity
- Speech and language difficulties
- Hand-biting or hand-flapping
- Hyper-flexible joints
- A large head and protruding ears, forehead, and chin
- Flat feet
- An elongated face
According to Zynerba, Zygel is:
the first and only pharmaceutically-produced cannabidiol, a non-euphoric cannabinoid, formulated as a patent-protected permeation-enhanced gel for transdermal delivery through the skin and into the circulatory system. Zygel is being developed for patients suffering from FXS, ASD, and 22q.
Researchers explored the safety, efficacy, and tolerability of Zygel in the Phase 2/3 CONNECT-FX trial. Altogether, 212 patients aged 3-17 enrolled. During the trial, patients received either Zygel or a placebo. Ultimately, researchers sought to understand whether treatment reduced abnormal or socially avoidant behaviors in children with FXS. In the end, the treatment was not found to reduce these behaviors.
At the same time, data from the extension study has shown that Zygel may still benefit certain patients with FXS. In particular, Zygel caused a 70% improvement in social avoidance scores for patients with a fully methylated FMR1 gene. Additionally, Zygel showed sustained tolerability during the extension study follow-up period. While the treatment is relatively safe and well-tolerated, some adverse reactions have occurred, with the most common being application site reaction.
Moving forward, Zynerba will continue to evaluate Zygel in other clinical trials, such as the Phase 3 RECONNECT study.