Background

This is an orally administered inhibitor of the β-secretase BACE1, the sheddase enzyme that cleaves APP and sets up subsequent γ-secretase cleavage leading to generation of Aβ species. The rationale behind this approach is that it will test the amyloid-cascade hypothesis of Alzheimer's disease and act as a disease-modifying therapy.

Findings

Three Phase 1 trials have been completed. In January 2012, a trial conducted in Strasbourg, France, concluded a test of RG7129 in 50 healthy men to assess safety and pharmacological parameters of single ascending doses given with or without food. This trial assessed plasma levels of amyloid biomarkers. In September 2012, a trial concluded evaluation of a 14-day course of multiple ascending doses in 36 patients, also in Strasbourg. This trial assessed RG7129 pharmacologic parameters across the adult age range starting at 18.  In June 2013, a trial in 42 participants in the United States concluded, which investigated the pharmacodynamics and pharmacokinetics of single doses of RG7129 in plasma and cerebral spinal fluid of healthy men. No results have been reported thus far.

In October 2013, Roche terminated development of this compound. Liver toxicity has been mentioned as the reason, but Roche issued no official explanation.