Cognitive outcomes in trials of two BACE inhibitors in Alzheimer's disease

Alzheimers Dement. 2020 Nov;16(11):1483-1492. doi: 10.1002/alz.12164. Epub 2020 Oct 13.


Introduction: The APECS and AMARANTH trials showed that beta-secretase (BACE) inhibitors verubecestat and lanabecestat failed to slow cognitive and functional decline in individuals with prodromal or early Alzheimer's disease. Here, the performance on secondary and exploratory cognitive measures in both studies is reported.

Methods: APECS (verubecestat) and AMARANTH (lanabecestat) were randomized, double-blind, placebo-controlled, parallel-group, 104-week clinical trials conducted by different sponsors. Measures included the 3-Domain Composite Cognition Score (CCS-3D), Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Letter/Category Fluency, and Digit Symbol Coding.

Results: Verubecestat showed worsening on the CCS-3D Total Score, Episodic Memory, and Attention/Processing Speed domains. Lanabecestat showed worsening on the RBANS Total Score, Immediate Memory, and Visuospatial/Constructional Indexes. Both BACE inhibitors showed worsening on Digit Symbol Coding and improvements on Letter/Category Fluency.

Discussion: In both studies, many measures showed treatment-associated cognitive worsening, whereas verbal fluency tasks showed improvement.

Trial registration: NCT01953601 NCT02245737.

Keywords: Alzheimer's disease; BACE inhibition; cognition; lanabecestat; verubecestat.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / drug therapy*
  • Cognition / drug effects*
  • Cyclic S-Oxides / therapeutic use*
  • Double-Blind Method
  • Female
  • Humans
  • Imidazoles / therapeutic use*
  • Male
  • Spiro Compounds / therapeutic use*
  • Thiadiazines / therapeutic use*
  • Treatment Outcome*


  • Cyclic S-Oxides
  • Imidazoles
  • Spiro Compounds
  • Thiadiazines
  • verubecestat
  • lanabecestat

Associated data