Cannabidiol transdermal gel for the treatment of fragile x syndrome: Post hoc responder analysis and pattern of efficacy on domains of the aberrant behavior checklist-FXS (ABCCFXS)

Abstract

Objective: This study evaluated the pattern of clinical efficacy of open-label ZYN002, experimental cannabidiol (CBD) transdermal gel, in the treatment of Fragile X Syndrome (FXS). Background: FXS is a neurodevelopmental condition characterized by repeat expansion in the FMR1 gene on the X chromosome. Previously, we documented open-label treatment with ZYN002 was well-tolerated and associated with improvement in behavioral symptoms and anxiety in patients with FXS. An improvement of at least 25% in individual domains of the Aberrant Behavior Checklist-FXS (ABC-C ) has been established as an important criterion in defining positive responder status in contemporary studies in FXS. The pattern of response to ZYN002 across multiple ABC-C domains may help to predict its possible future clinical utility. Design/Methods: This 12-week, phase 2, open-label study assessed ZYN002 in participants aged 6-7 years, with full FMR1 mutation, who showed suboptimal clinical response to standard of care. We explored efficacy by assessing change on all ABC-C domains (social avoidance, irritability, socially unresponsive/lethargic, hyperactivity, stereotypy, inappropriate speech), creating responder analyses and 'radar charts' to visualize change in each ABC-C domain. Results: Of the 20 enrolled participants, 18 completed the study. Maximal 25% responder rates on all domains of ABC-C on any visit ranged from 77.8 - 83%. Maximal 50% responder rates on all domains of ABC-C on any visit ranged from 55.6 - 77.8%. Baseline to endpoint 'radar charts' showing all ABC-C domains, with each domain independently represented its own normalized single axis, provided visual evidence of meaningful change Conclusions: The majority of FXS patients treated with open-label ZYN002 met an important criterion for response on the ABC-C . Simultaneous visualization of change across all measured domains of the ABC-C ('radar charts') provided evidence of more global, multidomain reduction in behavioral symptom burden, and may provide evidence to support the efficacy of ZYN002 CBD transdermal gel in FXS.L6330685482020-10-15 <br />