Synonyms: BACE1 inhibitor
Therapy Type: Small Molecule
Target Type: APP and Amyloid-Related (timeline)
Condition(s): Alzheimer's Disease, Mild Cognitive Impairment
U.S. FDA Status: Alzheimer's Disease (Phase 1), Mild Cognitive Impairment (Discontinued)
Company: Eisai Co., Ltd.
E2609 is a BACE, aka β-secretase enzyme inhibitor, which was developed with the rationale of interfering with the amyloid cascade upstream of Aβ peptide generation. At the 2012 AAIC conference in Vancouver, Canada, Eisai presented data to suggest that E2609 lowers Aβ concentration in the brain, CSF, and plasma of rats and guinea pigs, and that it lowers CSF and plasma Aβ in nonhuman primates (see Jul 2012 conference story).
Four Phase 1 trials were completed. They evaluated the safety and pharmacology of E2609 in a total of 141 healthy volunteers. One trial focused on bioavailability with food in particular. Eisai presented results from the first two studies at the 2012 AAIC conference. The single oral ascending-dose study of 5–800 mg drug showed a reduction of Aβ levels in plasma; a 14-day ascending-dose study of 25–400 mg showed a dose-dependent reduction of up to 80 percent in CSF Aβ levels.
According to Eisai, E2609 showed acceptable tolerability across all doses, with headache and dizziness the most common adverse events. A press release stated that no clinically significant safety concerns were observed following repeated oral dosing of up to 200 mg. Several cases of orolabial herpes relapse were observed in the 200 mg cohort, and safety findings in the 400 mg group were not disclosed.
Another trial tested seven different single oral doses in 65 people with mild cognitive impairment who had biomarker evidence of amyloid pathology, and measured CSF Aβ levels as a primary outcome measure. This trial was completed in October 2013 but not data have been disclosed.
A small Phase 1 study to understand how the body breaks down and eliminates E2609 is currently ongoing. For all clinical trials of E2609, see clinicaltrials.gov.
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