Zagotenemab (LY3303560; Eli Lilly, Indianapolis, IN), a monoclonal antibody targeting misfolded tau proteins, failed to significantly slow cognitive and functional decline in patients with early symptomatic Alzheimer disease (AD) according to results of the phase 2 PERISCOPE-ALZ (NCT03518073) clinical trial.

Conducted across 56 sites in North America and Japan, the study involved 360 participants aged 60 to 85 years with intermediate brain tau levels. Participants received either 1400 mg or 5600 mg of Zagotenemab or placebo via intravenous (IV) infusion every 4 weeks for 100 weeks.

The primary outcome, change on the Integrated AD Rating Scale (iADRS), showed a mean disease progression ratio of 1.10 for the low-dose group and 1.05 for the high-dose group, indicating no significant difference between Zagotenemab treatment and placebo. Secondary endpoints, including cognitive and functional measures, as well as imaging and plasma biomarkers, also failed to demonstrate evidence of pharmacodynamic activity or disease modification.

Additionally, adverse events (AEs) were more common in the Zagotenemab groups (85.1%) compared to placebo (74.6%), though no specific AE category was predominant.

Source: Fleisher AS, Munsie LM, Perahia DGS, et al. Assessment of efficacy and safety of Zagotenemab: results from PERISCOPE-ALZ, a phase 2 study in early symptomatic Alzheimer disease. Neurology. 2024;102(5):e208061. doi:10.1212/WNL.0000000000208061