One year of treatment with the cannabidiol gel ZYN002, being developed by Zynerba Pharmaceuticals, can provide sustained benefit to young patients with fragile X syndrome, data from a Phase 2 trial show.
Twelve children and adolescents treated with ZYN002 gel absorbed through the skin once daily for 12 months experienced significant improvements in core emotional and behavioral symptoms compared to before treatment.
Trial data were detailed in the poster “Transdermal Cannabidiol (CBD) Gel for the Treatment of Fragile X Syndrome” presented this month at the 57th Annual Meeting of the American College of Neuropsychopharmacology (ACNP) in Hollywood, Florida.
ZYN002 is the first and only cannabidiol product pharmaceutically manufactured as a patent-protected and permeation-enhanced clear gel, Zynerba states. It was designed to provide controlled delivery of its active compound (cannabidiol) into the bloodstream through the skin.
The ongoing Phase 2 trial, called FAB-C (which stands for “Treatment of Fragile X Syndrome Anxiety and Behavioral Challenges with CBD”; an NCT number was not evident), enrolled 20 patients with ages between 6 and 17 and with a genetically confirmed fragile X diagnosis.
During the first six weeks of treatment, researchers tested increasing doses of ZYN002, ranging from 50 mg up to 250 mg daily. Weeks seven through 12 were a maintenance period, during which patients were treated with an established dose.
A total of 18 patients completed the 12 weeks of treatment, two receiving ZYN002 at 100 mg and 16 who had moved to 250 mg. Thirteen patients moved into the 24-month extension study.
To date, 11 remain in that study and have now exceeded 12 months of treatment with ZYN002. Reasons given for leaving the trial were all not related to treatment, and included one patient whose eczema worsened and three others with administrative problems.
Patient evaluation using the Aberrant Behavior Checklist for Fragile X (ABC-CFXS) and Anxiety, Depression, and Mood Scale (ADAMS) revealed significant improvements in several parameters after 12 weeks of treatment, compared to assessments made at the study’s start. These included positive changes in social avoidance and manic/hyperactive behavior, depressive mood, general anxiety, compulsive behavior, as well as in irritability and inappropriate speech.
Further analysis of long-term impact of ZYN002 showed sustained benefits through 12 months of treatment.
A 77.2% improvement in social avoidance behaviors was seen at 12 months of treatment, as measured by the ABC-CFXS score, compared to 57.9% improvement at three months.
“I am encouraged to see that improvements in FXS-associated emotional and behavioral symptoms after 12 months of treatment with ZYN002 are consistent with those seen at three and nine months; these data continue to suggest the potential for sustained responses that may be conserved over extended use of the drug,” Steven Siegel, MD, PhD, professor and chair of psychiatry and behavioral sciences at Keck School of Medicine, said in a press release.
“Improvements in these behaviors may enhance the child’s capacity for interaction and engagement with their peers, families, teachers and caregivers,” he added.
In general, the treatment was safe and well-tolerated by patients, with no serious adverse events reported. The most common treatment-related side effects were gastroenteritis (inflammation of the intestines) and upper respiratory tract infection, which were mild to moderate in severity.
Zynerba is further exploring ZYN002’s potential, against placebo, in a larger patient population in the ongoing Phase 2/3 CONNECT-FX trial (NCT03614663). The study is currently recruiting fragile X syndrome patients, age 3-18, at clinical sites in Australia, New Zealand, and the United States.
The company expects to announce top line results from CONNECT-FX during the second half of 2019.
“These data are promising, and I am enthusiastic about the potential opportunity for ZYN002 in these patients,” Siegel said. “I look forward to the results of the double blind, placebo-controlled CONNECT-FX study next year.”
“Our aspirations and expectations are clear: To work closely with the U.S. Food and Drug Administration to expand the opportunity for pharmaceutically-developed CBD treatments that meet their rigorous medical and manufacturing standards, and in doing so, continue toward our goal of addressing significant unmet medical needs in neuropsychiatric disorders,” Armando Anido, chairman and CEO of Zynerba, said in another press release.
The company is planning to extend the clinical development of ZYN002 transdermal gel to include patients with autism spectrum disorder and 22q deletion syndrome in addition to its fragile X and developmental and epileptic encephalopathy programs.