vTv's azeliragon fails to improve Alzheimer's symptoms in phase 3

Another day, another Alzheimer's treatment bites the dust. This time, it's vTv Therapeutics' azeliragon, which missed both of its co-primary endpoints in a phase 3 trial of patients with mild Alzheimer's. 

The treatment failed to beat out placebo in improving cognitive or functional outcomes measured by the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and the Clinical Dementia Rating Scale Sum of Boxes (CDR-sb), the company said in a statement. In fact, the treatment group posted a worse decline in ADAS-Cog than the placebo group—4.4 versus 3.3 points from baseline—while the decline in CDR-sb score was identical for both groups. vTv plummeted 66% in after-hours trading. 

The company is now ditching all ongoing clinical studies of azeliragon but expects a "substantial number" of patients in an identical phase 3 trial to have completed 12 months of treatment under the study protocol. vTv will be taking a good look at the data from both trials in the coming weeks, the company said. 

“We will continue to analyze the data sets and trends within subgroups from both Part A and Part B to determine if there are potential benefits or future uses and applications for azeliragon,” said CEO Steve Holcombe in the statement. “On behalf of vTv Therapeutics, we’d like to extend our most sincere and heartfelt gratitude to study participants, their families, physicians and caregivers for their commitment to this important study.”  

In July 2015, vTv priced its IPO at $117 million, at the low end of the range. It had hoped to raise more than $150 million. It built its case around azeliragon, which Pfizer dropped after a trial using a 20-mg dose was stopped after signs of cognitive worsening developed in patients. A lower, 5-mg dose, however, showed improvement in ADAS-Cog scores, which is the effect the company was looking for.

"This is a very, very tight window between what could be a good effect and what is certainly a very bad one," wrote biotech blogger Derek Lowe, at vTv's IPO. "Which is surely why Pfizer dropped the compound like it was giving off gamma rays and has not returned to it."

Azeliragon is just the latest Alzheimer's drug to crash and burn in phase 3. In February, Merck pulled the plug on a phase 3 trial of its BACE1 inhibitor verubecestat in prodromal Alzheimer's after an interim review. And the study halt came after the Big Pharma had already ended a trial in patients with more advanced forms of the disease after seeing similarly lackluster data. 

Editor's note: This story has been updated to correct this history of azeliragon. It previously conflated the drug with Axovant's intepirdine.