Zynerba sinks after total failure in phase 2 cannabidiol trial

Zynerba is also trialing the drug in osteoarthritis and Fragile X syndrome.(Getty Images)

A phase 2 trial of Zynerba Pharmaceuticals’ transdermal cannabinoid candidate has missed all its endpoints. The failure of the study to hit a single goal or show a dose response raises big doubts about the drug's prospects—and wiped more than 55% off Zynerba’s stock price.

Investigators enrolled 188 adults with refractory epilepsy with focal seizures and randomized them to receive one of two doses of ZYN002 or placebo. Zynerba hoped to show its cannabidiol gel cut focal seizures but ultimately it fell short of that goal.

Participants who received the low dose of ZYN002 experienced an 18.4% median reduction in focal seizures. The figures for the high dose and placebo were 14.0% and 8.7%, respectively. That resulted in the trial missing its primary endpoint. The endpoint miss and lack of a dose-dependent response may point to the failure of the delivery system to generate the needed pharmacokinetic profile. 

The secondary endpoints brought no solace to Zynerba. ZYN002 failed to beat placebo against any of the secondary goals. That left Zynerba clinging to the safety data as the sole positive. 

“Importantly, today’s results demonstrated ZYN002 to have a very favorable safety and tolerability profile, which is an encouraging fact as we look to develop ZYN002 as a treatment for a wide range of indications,” Zynerba CEO Armando Anido said in a statement.

Zynerba is trialing ZYN002 as a treatment for osteoarthritis and Fragile X syndrome. Yet, while the epilepsy safety data may be positive for these studies, the upbeat readthrough is overshadowed by the wall-to-wall efficacy fail. 

Given GW Pharma has shown its cannabidiol affects seizures, Zynerba’s data suggest its delivery system may be to blame. If that is the case, there is little reason to think ZYN002 will perform better in the phase 2 osteoarthritis and Fragile X trials. Data from those studies are due later this year. 

The failure of ZYN002 to move the needle in those trials would leave Zynerba looking to ZYN001 to secure it a brighter future. With the THC prodrug patch yet to clear phase 1, that would represent a blow to Zynerba’s near-term prospects.