Name: AZD3293
Synonyms: LY3314814, 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: AstraZeneca, Eli Lilly & Co.


AZD3293 is an inhibitor of BACE1, the β-secretase sheddase that cleaves the APP protein to release APP's C99 fragment. This fragment then becomes a substrate for subsequent γ-secretase cleavage and Aβ peptide generation. The rationale is that inhibiting BACE1 will reduce amyloid-related toxicity in Alzheimer's disease. AZD3293 is one of several BACE1/2 inhibitors currently in development. Preclinical data have not been formally published. AZD3293 is administered in tablet form.


In December 2012, AstraZeneca started a Phase 1 study that evaluated the safety and pharmacological effects of single doses of oral AZD3293 in 72 healthy volunteers. Doses ranged from 1–1,000 mg. In 2013 and 2014, six additional Phase 1 studies in the United States and Japan further evaluated safety, tolerability, metabolism, and potential drug interactions of single and multiple ascending doses of a tablet and an oral formulation in both elderly volunteers and Alzheimer's patients. Effects on biomarkers in plasma and CSF were also measured. The results have not yet been published in peer-reviewed journals, but the company has reported at scientific conferences that the inhibitor appeared safe and strongly reduced CSF Aβ levels (see Mar 2014 news story).

In September 2014, AstraZeneca and Eli Lilly announced that they would jointly develop AZD3293, with AstraZeneca handling manufacturing and Eli Lilly leading clinical trials (see company press release).

The clinical development of this compound will largely skip over Phase 2, running no medium-size Phase 2 trials but instead a large, pivotal Phase 2/3 trial in 2,202 targeted patients.  Called AMARANTH, this trial will compare AZD3293 to placebo given for two years. In December 2014, this multicenter trial began enrolling people who meet NIA-AA criteria for MCI due to AD or mild AD. Each participant or his or her partner must report worsening in the past six months, and the participant's MMSE must be above 21 at screening. To ascertain that they have brain amyloid accumulation, participants will undergo either an amyloid PET scan or a lumbar puncture and continue in respective substudies monitoring those markers for treatment response. The trial will compare two doses given once daily as a tablet to placebo, and measure success by change from baseline on the clinical dementia rating sum of boxes (CDR-SOB). The ADAS-cog and ADCS-ADL are secondary outcome measures, along with other clinical markers as well as change in CSF markers, functional and amyloid PET, and MRI. This study is set to run for five years. 

In 2015, 3 additional phase 1 trials in a total of 157 healthy volunteered evaluated the interaction of this BACE inhibitor with certain drugs commonly prescribed in the elderly, such as the blood thinners warfarin and dabigatran, the sedative midalozam, as well as simvastatin and donepezil.

For all clinical trials of this compound, see

Clinical Trial Timeline

  • Phase 2/3
  • Phase 3
  • 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
Eli Lilly & Co., AstraZeneca NCT02245737
Eli Lilly & Co., AstraZeneca NCT02783573


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News Citations

  1. BACE Inhibitor Heads for Phase 2/3 Trials

External Citations

  1. company press release

Further Reading