Zynerba flunks another major trial, all but ending Fragile X hopes – Endpoints News

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.

Ar­man­do Anido

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.

Source: https://endpts.com/zynerba-flunks-another-phii-trial-all-but-ending-fragile-x-hopes/