Ceperognastat in Early Symptomatic Alzheimer Disease: A Randomized Clinical Trial.

Ceperognastat failed to significantly slow disease progression in early symptomatic Alzheimer disease at 100 weeks, despite reducing brain volume loss.

• Why it matters: Effective treatments for early Alzheimer disease are urgently needed to prevent or delay cognitive decline, but current options are limited, highlighting the importance of exploring new therapeutic targets like tau pathology.
• What they did: A double-blind, randomized phase 2 trial tested 0.75 mg and 3 mg doses of oral ceperognastat versus placebo in 259 participants with biomarker evidence of tau pathology, measuring cognitive and imaging outcomes over 100 weeks.
• The result: While ceperognastat did not improve primary cognitive scores, the 3 mg dose was associated with less brain volume loss and a smaller increase in tau PET signals, but also higher rates of serious adverse events, indicating limited efficacy and safety concerns.