Synonyms: BACE inhibitor
Therapy Type: Small Molecule (timeline)
Target Type: Amyloid-Related (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 2)
Company: Biogen, 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 non-human primates (see Jul 2012 conference story). In March 2014, Eisai and Biogen Idec signed a collaboration agreement to jointly develop E2609.
As of March 2015, eight Phase 1 trials had been completed. They evaluated the safety and pharmacology of E2609 in nearly 500 healthy volunteers and people with early Alzheimer's disease. Eisai presented results from the first two studies at the 2012 AAIC conference. The single oral ascending-dose study of 5 to 800 mg drug showed a reduction of Aβ levels in plasma; a 14-day ascending-dose study of 25 to 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 no data have been disclosed.One study compared safety and pharmacology of E2609 in Japanese and Caucasian people, and one tested if the inhibitor affects the function of the heart. One trial evaluated interactions with drugs commonly prescribed to the elderly, another one focused on bioavailability with food.
In November 2014, Eisai started a large phase 2 dose-finding study in 700 people with MCI due to AD or prodromal AD who have a positive amyloid PET scan. This 7-arm trial will compare an 18-month course of 3 different doses to placebo in people whose dementia has been classified as being at the MCI/prodromal stage, and 2 doses to placebo in people whose dementia has been staged at mild AD. The primary outcome is change from baseline in the prodromal group on a new cognitive/clinical measure developed for pre-dementia/prodromal called Alzheimer's Disease Composite Score (ADCOMS) (see Oct 2014 CAMD meeting). Secondary outcomes include hippocampal atrophy and CSF biomarkers, as well as change on ADCOMS in the mild AD group.
For all clinical trials of E2609, see clinicaltrials.gov.
Clinical Trial Timeline
- Phase 2
- Study completed / Planned end date
- Planned end date unavailable
- Study aborted
|Eisai Co., Ltd.||NCT02322021||
No Available Further Reading