Efficacy, Immunogenicity, Safety, and Tolerability of AADvac1 in Alzheimer Disease: A Systematic Review and Meta-Analysis of Placebo-Controlled Trials.

BACKGROUND

This systematic review and meta-analysis aimed to evaluate the efficacy, humoral immunogenicity, safety, and tolerability of AADvac1 an active tau-targeted immunotherapy in patients with Alzheimer disease (AD) confirmed by amyloid and tau pathology.

METHODS

We searched MEDLINE, Embase, Scopus, and CENTRAL from inception to March 2025 for randomized placebo-controlled trials assessing AADvac1 in AD. Eligible studies included adult patients with biomarker-confirmed AD. Risk of bias was assessed using the Cochrane RoB 2 tool. Meta-analyses were conducted using random-effects models.

RESULTS

Five trials (n=667) were included, of which 391 received AADvac1 and 276 received placebo. Pooled analyses showed a robust IgG response (IgG seroconversion rate: 99%, 95% CI: 95%-100%) with predominance of IgG1 and IgG3 subclasses. AADvac1 did not improve MMSE (MD: -0.49; 95% CI: -2.40 to 1.41) but showed trends favoring improvement in ADAS-Cog11 and verbal fluency. The vaccine was well tolerated, with injection site reactions being the most frequent adverse event. No increased risk of serious infections, cerebral edema, or mortality was observed.

CONCLUSIONS

AADvac1 demonstrates robust immunogenicity and an acceptable safety profile in early-phase trials. Cognitive benefits remain inconclusive. Larger, long-term trials are needed to confirm its clinical efficacy and long-term safety in AD.