NEW ORLEANS — Treatment with ZYN002, an investigational transdermal cannabidiol (CBD) gel, was well-tolerated and consistently effective for adults with focal epilepsy, according to study data presented at the 72nd Annual Meeting of the American Epilepsy Society, held November 30 to December 4, 2018.
Recently studied CBD products in children with refractory epilepsy have administered via the oral route. ZYN002, however, is the first permeation-enhanced pharmaceutical transdermal CBD gel developed.
The phase 2A, randomized, double-blind, placebo-controlled STAR 1 (Synthetic Transdermal CAnnabidiol for the TReatment of Epilepsy; N=174) study evaluated the efficacy and safety of ZYN002 195mg, ZYN002 390mg or placebo in adults (ages 18 to 70 years) with focal seizures.
Patients who completed the 12-week study were able to continue into the 24-month open-label extension STAR 2 study (N=171). In STAR 2, patients were converted from their blinded dose to open-label 390mg daily; they were allowed to increase their dose to 585mg and 780mg daily or decrease to 195mg daily.
Study authors measured the percent reduction from STAR 1 baseline at months 3, 6, 9, 12, 15, and 18 of STAR 2. Regarding safety, patients’ clinical labs, physical exam, and adverse events (AEs) were assessed. At the end of STAR 1, patients who received ZYN002 did not demonstrate a statistically significant reduction in focal seizures vs placebo. Of the 171 patients enrolled in STAR 2, 95 discontinued the study as of July 31, 2018.
An increase in efficacy rates with ZYN002 was seen over the 18 months (mean percent change in seizure rates: -55%) in the remaining cohort (n=63). For all treated patients, the median change in seizure rates were -25% at month 3, -40% at month 6, -48% at month 9, -52% at month 12, and -57% at month 15.
For the cohort group (n=63), the median percent change in seizure rates were -49%, -53%, -55%, -52%, -54%, and -55% for Months 3, 6, 9, 12, 15, and 18, respectively.
“As the cohort group had a substantial reduction at Month 3 that was maintained to Month 18, this suggests that early dropouts could account for the improved efficacy,” noted the authors. Patients in the ZYN002 390mg treatment group showed the most consistent seizure reduction through month 18 whereas the 585mg and 780mg groups experienced only resulted in some added benefit.
In general, ZYN002 was well-tolerated. Serious adverse events were thought to be possibly treatment-related, which included seizures (n=2) and increased anxiety (n=1); one death was reported after the Month 15 visit. In addition, there were no elevations in alanine aminotransferase and aspartate aminotransferase levels >3 times upper limit of normal were seen.
O’Brien T, Berkovic SF, French J, et al. Synthetic Transdermal Cannabidiol for the Treatment of Focal Epilepsy in Adults. Presented at: 72nd Annual Meeting of the American Epilepsy Society; November 30-December 4, 2018; New Orleans, LA. Poster 2.253.
This article originally appeared on Neurology Advisor