Zygel (ZYN002) — a cannabis-based gel formulation developed by Zynerba Pharmaceuticals — can significantly reduce seizures by up to six months in children and adolescents with developmental and epileptic encephalopathies, according to Phase 2 trial data.
Developmental and epileptic encephalopathies, or DEE, is an umbrella term that includes a heterogeneous group of rare pediatric epilepsy syndromes, such as Dravet and Lennox-Gastaut syndrome, among others.
The open-label BELIEVE 1 clinical trial (NCT03802799) was designed to explore the long-term safety and efficacy of Zygel in children and adolescents with DEE. To date, the study has enrolled, by invitation, 48 participants between 3 and 16 years old, who had confirmed DEE as classified by the International League Against Epilepsy.
The participants were initially dosed daily with 250 or 500 mg of Zygel, based on their weight, but the dosage could be increased up to a maximum of 1,000 mg daily. The treatment was directly applied to the skin (transdermal delivery) on the shoulders and upper arms.
Zygel was generally well-tolerated, and the safety profile was consistent with data from previous clinical studies.
One patient had to discontinue treatment due to an adverse reaction at the application site, and seven others stopped treatment as a result of consent withdrawal or perceived lack of efficacy.
During six months of treatment, 96% of the children experienced a treatment-emergent adverse event, and 60% had a treatment-related adverse event, most of which were mild to moderate in severity. Most common adverse events included application site dryness or pain, and sleepiness.
Of the 46 patients who completed all the required daily reports, 33 (72%) had focal impaired-awareness seizures (FIAS, formerly known as complex partial seizures) and/or convulsive seizures before starting the treatment.
FIAS are a type of seizure that affects only one part of the brain, in contrast to generalized seizures that seem to affect all brain areas. FIAS are usually short in duration, and the individual remains alert and able to interact.
Baseline data showed that the 33 children and adolescents experienced a mean seizure count of 64 FIAS and/or convulsive seizures, and a median count of 8.2.
After two months of treatment, seizure frequency was reduced by more than 44% (median reduction) and up to 51% at month six. Approximately 55% of patients with FIAS and/or convulsive seizures experienced a 50% or higher median reduction in seizures after six months of treatment with Zygel.
“We are encouraged by the positive top line results of the BELIEVE 1 trial of Zygel in children and adolescents with DEE, and we believe these data represent an important step forward for these patients and their families,” Armando Anido, Zynerba’s chairman and CEO, said in a news release.
Those with Dravet syndrome or Lennox-Gastaut syndrome who experienced FIAS and/or convulsive seizures (11 patients) showed a 51% median reduction in seizure frequency after six months of treatment. Sixty percent of patients with these syndromes experienced a 50% or more median reduction in FIAS or convulsive seizures after six months of treatment.
Among the study participants, 13 had seizures that were not classified as FIAS and/or convulsive types. The number of individual seizure types in these patients was too small for the researchers to draw definitive conclusions so additional analyses are necessary.
Daily reports from parents and caregivers revealed that 58% of the participants showed improvements in vitality, 47% in cognition and concentration, and 44% in socially avoidant behaviors. The treatment also seemed to allow children to attend school more often in 28% of the cases.
Approximately 26% of parents and caregivers reported difficulty in applying the gel on their child. Some reported that Zygel took too long to dry.
“The data from the BELIEVE 1 clinical trial are promising and suggest that Zygel may reduce seizure frequency in many types of difficult to treat developmental and epileptic encephalopathies and improve important behavior deficits, alertness, social interactions, and enable the child to be well enough to attend school more consistently,” said Ingrid Scheffer, PhD, FRACP, professor and chair of pediatric neurology research at the University of Melbourne, and an investigator in the BELIEVE 1 trial.
Once Zynerba completes its data analyses of Zygel, the company plans to seek approval of the treatment from regulatory agencies.
“We intend to seek a meeting with the U.S. Food and Drug Administration, likely in the first half of next year, to discuss the clinical pathway to approval [of Zygel],” Anido said.