Zynerba’s CBD drug has failed its fourth trial in as many years.
In a pivotal Phase III trial, their lead compound failed to significantly improve behavioral symptoms in patients with Fragile X syndrome, missing both the primary endpoint and three different secondary endpoints.
The failure is the latest in a series of setbacks for a company that once hoped to rival top cannabis biotech GW Pharma. Five years ago, as CBD drug development began bubbling, the Pennsylvania biotech went public on the promise of making THC, cannabis’s active ingredient, without the need for plants, allowing for cheaper, more scalable drugs. In giving the drug by gel rather than orally, they also promised to reduce side effects.
Since then, though, while GW Pharma emerged with the first CBD approval, Zynerba’s drugs have struggled mightily in the clinic, missing key endpoints and sometimes failing to show dose-dependent responses. Plans for an epilepsy and osteoarthritis drug fell away with clinical failures in 2017. A year later, so did a patch that was meant to deliver their THC through the skin.
Zynerba’s noteworthy success was a Phase II trial that seemed to show a 46% improvement in symptoms among 20 patients with the genetic neurological disorder Fragile X. That trial, though, had no control arm, leaving doubts about how effective the drug was.
The 212-person trial announced Tuesday was the first placebo-controlled study to test Zynerba’s CBD for that condition, and the study appeared to vindicate the doubters. Patients on the drug did not score significantly better on the aberrant behavior checklist, the irritability subscale, the socially unresponsive/lethargic subscale, or in Clinical Global Impression.
The company’s stock was cut nearly in half Tuesday morning, from $6.54 to $3.48.
As he has after past failures, CEO Armando Anido tried to spin the lone positive result of the trial into a victory. Although it wasn’t a primary or secondary endpoint, the company pre-planned an analysis of the patients whose FMR1 gene — the orchestral gene in Fragile X — and were fully methylated. In those patients, the results were statistically signficiant, albeit narrowly so.
“The results from CONNECT-FX identified a significant patient population who responded well to Zygel and may provide us with a pathway towards licensure,” CEO Armando Anido said in a statement, noting they estimate around 60% of fragile X patients are fully methylated. “We intend to discuss the results of the study with the FDA as soon as possible.”
The company said similar things after the osteoarthritis trial produced one positive result on a composite endpoint. The indication is no longer listed on their official pipeline.