vTv’s azeliragon is latest Alzheimer’s drug failure

The North Carolina-based firm had been trying a different approach than the big pharma companies and had attempted to inhibit a protein called Receptor for Advanced Glycation Endproducts (RAGE).

Activation of the cell membrane protein had been linked to buildup of mutant amyloid-beta in the brain, thought to play a part in development of Alzheimer’s disease.

But unfortunately vTv has drawn a blank with this approach, as the STEADFAST trial of azeliragon missed its two main goals.

The company is stopping current clinical studies involving azeliragon, including a second arm of STEADFAST and an open-label extension study.

Patients taking azeliragon compared with placebo did not improve in cognitive or functional outcomes as measured by the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog) and the Clinical Dementia Rating Scale Sum of Boxes (CDR-sb).

The STEADFAST study is comprised of two independent and identical randomised, double-blind, placebo-controlled Phase 3 trials, known as Part A and Part B.

The azeliragon treated group in Part A had a 4.4 point decline from baseline in ADAS-Cog and a 1.6 point decline from baseline in CDR-sb compared to a placebo decline of 3.3 and 1.6 respectively.

These differences were not statistically significant and vTv said azeliragon was generally well-tolerated with a 25% withdrawal rate over 18 months that was similar in both the placebo and treatment arms.

vTv said a substantial portion of patients in Part B of STEADFAST will have completed 12 months of treatment under the study protocol.

The company will evaluate subset data from Part A and the data from Part B over the coming weeks to see if there are any potential benefits or future uses for azeliragon.

CEO Steve Holcombe said: "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."

There has been a string of Alzheimer’s drug failures in the past year or so and no progress in finding new treatments for the disease for around 15 years.

In February Boehringer Ingelheim axed development of a phase 2 candidate after a trial failure, and Axovant’s much-anticipated intepirdine failed in a late stage trial in September.

Merck & Co last year stopped a trial of its BACE inhibitor verubecestat, saying that there was "virtually no chance" of it helping patients with mild to moderate Alzheimer’s.

Hopes are resting with drugs such as Biogen’s aducanumab, which works against amyloid and could report preliminary phase 3 results next year.

Roche is also soldiering on with crenezumab in phase 3, another drug targeting amyloid.

And despite the setbacks a report by ResearchersAgainstAlzheimer’s last year found there are dozens of drugs in the pharma pipeline that could become new treatments if trials are successful.

The trial failure is bad news for vTv, which saw its share price plummet on the news. The company has a number of other molecules in its pipeline, including TTP399, a novel glucokinase activating treatment for type 2 diabetes, but doesn’t have any further Alzheimer’s candidates.

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