Zynerba Pharmaceuticals, Inc. (Nasdaq: ZYNE) published the results from its open-label Phase 2 BELIEVE (Open-Label Study to Assess the Safety and Efficacy of Zygel (ZYN002) Administered as a Transdermal Gel to Children and Adolescents with Developmental and Epileptic Encephalopathy) study in the Journal of the American Medical Association (JAMA) Network Open. The gel is seen as an alternative to patients where oral drug delivery is a challenge due to the seizures.
The study demonstrated a 58% median monthly reduction in seizures at month 5, and 43.5% reduction over the 6.5 month study period (the primary efficacy endpoint). In addition, the parents/caregivers noted improvements in social or interpersonal engagement and irritability (77%); alertness, energy, and sleep (53%); and cognition or concentration (47%).
“DEEs are the most severe group of epilepsies and are usually drug-resistant. Antiseizure medications are usually administered orally, which can be extremely challenging in children with behavioral and cognitive problems. Non-oral therapies are needed to provide an alternative route to deliver medications to control seizures and improve developmental outcomes,” said Ingrid E. Scheffer, MBBS, PhD, FRS, Laureate Professor, and chair, Pediatric Neurology Research, University of Melbourne, and the lead investigator in the BELIEVE study. “The data from the BELIEVE study are promising and suggest that Zygel may be a safe and well-tolerated option to improve seizure control, challenging behaviors and other symptoms associated with DEEs.”
Forty-eight (48) patients with a mean age of 10.5 years were enrolled in BELIEVE and included in the safety analysis. 60% had at least one treatment-related adverse event (AE) over the 6.5 month trial period and 96% of these AE’s were mild or moderate. During the treatment period, 10 patients (21%) reported serious adverse events (SAEs). Two SAEs were considered to be possible treatment-related: nonconvulsive status epilepticus and lower respiratory tract infection, in separate patients. All SAEs resolved, and none resulted in alteration of study medication. The study warned that there was no control group and so it is impossible to know how much was due to the placebo effect and the desire for cannabis products to work.
The authors indicated that the incidence of AEs in this study, particularly related to infections, was likely due to the high baseline rate of complex morbidities and seizure severity of these patients at study onset, and to the relatively long, 6.5-month duration of the trial over which events were collected. The study was supported by Zynerba.