Dissemination, Science

Bump in the Road or Disaster? BACE Inhibitors Worsen Cognition

Merck shook the field with news that people on verubecestat scored worse than those on placebo.

Currently, hopes for an Alzheimer’s prevention therapy hang on BACE inhibitors that squelch generation of Aβ peptides. When these compounds failed to slow cognitive decline in symptomatic patients, researchers argued that they might work at earlier disease stages, before neurodegeneration has become entrenched. Alas, at the 11th Clinical Trials on Alzheimer’s Disease conference, held October 24–27 in Barcelona, Spain, researchers at Merck shook the field with the stunning announcement that in a Phase 3 trial, people with prodromal AD who took the inhibitor verubecestat scored worse on cognitive tests than those on placebo. Michael Egan of Merck reported that the effect was small, but significant. The cognitive deficit appeared at the earliest time point and did not grow over time, nor did it appear to correlate with increased neurodegeneration.

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