Azeliragon

Drug Overview

Azeliragon is an orally available small molecule that acts as an inhibitor of the receptor for advanced
glycation endproducts (RAGE). RAGE is a cell surface receptor implicated in many processes underlying
Alzheimer’s disease development and progression, including amyloid-beta transport into the brain,
chronic inflammation, tau phosphorylation, and neurotoxicity. Therefore, by interfering with RAGE’s
ligand bindings, azeliragon has the potential to slow down the progression of cognitive decline in
patients with mild to moderate Alzheimer’s disease (vTv Therapeutics, 2015a).
vTv Therapeutics is currently conducting a pivotal Phase III trial in mild Alzheimer’s disease under a
Special Protocol Assessment (SPA) with the US Food and Drug Administration (FDA). Topline results
are expected in mid-2018, which if successful, will prompt a New Drug Application (NDA) for
azeliragon to the FDA by the end of 2018 (Biomedtracker, 2015). Azeliragon has fast track designation
for the treatment of Alzheimer’s disease (vTv Therapeutics, 2013).

Analyst Outlook

While azeliragon’s (vTv Therapeutics) Phase IIb study was discontinued as the result of a negative
futility analysis, potential benefits for longer-term treatment emerged during patient follow-up.
Although these findings prompted the launch of a Phase III trial, vTv Therapeutics’ decision to progress
azeliragon’s development is speculative, and even if the trial does succeed, there are competitive
hurdles to overcome. Nevertheless, azeliragon has some unique features, such as its broad mechanism
and oral delivery, which could enhance its commercial appeal.