Name: Elenbecestat
Synonyms: E2609, 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 3)
Company: Biogen, Eisai Co., Ltd.


Elenbecestat is a small-molecule inhibitor of BACE, aka the β-secretase enzyme. It was developed with the rationale of interfering with the amyloid cascade upstream of Aβ peptide generation. BACE inhibition is sometimes envisioned as long-term maintenance therapy to limit Aβ production after an initial round of immunotherapy to remove existing amyloid deposits. 

At the 2012 AAIC conference in Vancouver, Canada, Eisai presented data to suggest that elenbecestat 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 news). Eisai developed this compound preclinically, and in March 2014 signed an agreement with Biogen to collaborate in its clinical development.


As of March 2015, eight Phase 1 trials had been completed. They evaluated the safety and pharmacology of elenbecestat 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, elenbecestat 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 whether 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 seven-arm trial will compare an 18-month course of three different doses to placebo in people whose dementia has been classified as being at the MCI/prodromal stage, and two 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 predementia/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. This trial is set to run until January 2017.

In August 2016, a ninth Phase 1 trial was added to compare the pharmacokinetics and metabolism of the inhibitor in people with normal versus impaired liver function.

On October 31, 2016, Eisai announced that it had begun enrolling people into the first study of its Phase 3 program of elenbecestat, called MISSION AD. MISSION AD1, aka study 301, is a global trial to evaluate a two-year, 50 mg once-a-day course of E2609 in 1,330 patients with biomarker-confirmed early Alzheimer’s disease. According to a company press release, the primary endpoint will be Clinical Dementia Rating Sum of Boxes (see company press release). 

As of November 2016, no study results had been posted on, or published in peer-reviewed journals yet.

For all clinical trials of elenbecestat, see

Clinical Trial Timeline

  • Phase 2
  • Study completed / Planned end date
  • Planned end date unavailable
  • Study aborted
Sponsor Clinical Trial 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 2026 2027 2028
Eisai Co., Ltd. NCT02322021


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News Citations

  1. Wave of New BACE Inhibitors Heading to Phase 2

External Citations

  1. Oct 2014 CAMD meeting
  2. company press release

Further Reading


  1. . The BACE1 inhibitor verubecestat (MK-8931) reduces CNS β-amyloid in animal models and in Alzheimer's disease patients. Sci Transl Med. 2016 Nov 2;8(363):363ra150. PubMed.