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Phase II/III GAIN trial results: atuzaginstat for disease modification in Alzheimer’s disease

Michael Detke, MD, PhD, Cortexyme, South San Francisco, CA, shares the top-line data of the Phase II/III GAIN trial testing the efficacy of atuzaginstat for disease modification in mild-moderate Alzheimer’s disease. Atuzaginstat is a small molecule, highly selective, brain penetrant lysine-gingipain inhibitor, designed based on the gingipain hypothesis, which proposes that Porphyromonas gingivalis (Pg) acts in Alzheimer’s pathogenesis via the release of toxic protease virulence factors (gingipains). By targeting gingipains, it is thought that atuzaginstat may be able to prevent the neuronal damage caused by Pg infection. The GAIN trial randomized over 640 patients to receive low- or high-dose atuzaginstat or placebo, assessing ADAS-Cog 11 and ADCS-ADL as co-primary endpoints. The results showed that in the overall intention-to-treat population, there was no significant difference in these measures between the treatment and placebo arms. However, when patients were assessed according to Pg infection status, a statistically significant slowing of disease progression was seen in the treatment arms in patients with higher infection levels, reflected by ADAS-Cog measures. Additionally, changes in Pg DNA levels in saliva significantly correlated with clinical outcomes during and following treatment. A confirmatory trial will take place in patients with mild-moderate Alzheimer’s with Pg infection. This interview was recorded on an online conference call with The Video Journal of Dementia (VJDementia).