Verubecestat APECS trial in prodromal AD also failed; cognitive worsening replicated in the earlier-stage population. Class concern about BACE1 inhibitor cognitive harm — likely off-target via non-APP BACE1 substrates (e.g. neuregulin-1, seizure protein 6).

Evidence span

Verubecestat APECS trial in prodromal AD also failed; cognitive worsening replicated in the earlier-stage population. Class concern about BACE1 inhibitor cognitive harm — likely off-target via non-APP BACE1 substrates (e.g. neuregulin-1, seizure protein 6).

From Michael Egan et al. 2019, New England Journal of Medicine

Method & conditions

Evidence type

experimental

Method

manual state transition; placebo-controlled clinical trial where source reports control arm

Species

Homo sapiens

Conditions

Human, prodromal AD; verubecestat oral BACE1 inhibitor; n=1454. APECS (NCT01953601).

Replicated

not yet

Confidence basis

operator-supplied frontier prior; review required