Abstract |
Increasing evidence supports the role of the Receptor for Advanced Glycation Endproducts (RAGE) in the pathology of Alzheimer's disease. Azeliragon ( TTP488) is an orally bioavailable small molecule inhibitor of RAGE in Phase 3 development as a potential treatment to slow disease progression in patients mild AD. Preclinical studies in animal models of AD (tgAPPSwedish/London) have shown azeliragon to decrease Aβ plaque deposition; reduce total Aβ brain concentration while increasing plasma Aβ levels; decreases sAPPβ while increasing sAPPα; reduce levels of inflammatory cytokines; and slow cognitive decline and improve cerebral blood flow. In the Phase 2b study, 18-months treatment in patients with mild-to-moderate AD indicated a baseline to endpoint change in ADAS-cog of 3.1 points in favor of drug. A greater magnitude of effect was evident in the sub-group of patients with mild AD (MMSE 21-26) with a baseline to endpoint change of 4 points on the ADAS-cog in favor of azeliragon and a 1 point change in CDR-sb in favor of drug. Azeliragon 5 mg/day delayed time to cognitive deterioration (7-point change in ADAS-cog from baseline, logrank p=0.0149). Based on promising results from the Phase 2b study, a Phase 3 registration program (STEADFAST) is being conducted under a Special Protocol Assessment from FDA. The ongoing Phase 3 program, if successful may demonstrate azeliragon can slow cognitive decline in mild AD patients.
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Authors | A H Burstein, M Sabbagh, R Andrews, C Valcarce, I Dunn, L Altstiel |
Journal | The journal of prevention of Alzheimer's disease
(J Prev Alzheimers Dis)
Vol. 5
Issue 2
Pg. 149-154
( 2018)
ISSN: 2426-0266 [Electronic] Switzerland |
PMID | 29616709
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
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Chemical References |
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Topics |
- Administration, Oral
- Alzheimer Disease
(complications, drug therapy)
- Animals
- Cognitive Dysfunction
(complications, drug therapy)
- Humans
- Imidazoles
(administration & dosage, pharmacology, therapeutic use)
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