Name: CNP520
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 2/3)
Company: Amgen, Inc., Novartis Pharmaceuticals Corporation


CNP520 is an oral, small-molecule inhibitor of the aspartyl protease BACE designed to reduce Aβ production to prevent or treat Alzheimer's disease. BACE1 is the β-secretase enzyme that cleaves the APP protein to release its C99 fragment, which gives rise to various species of Aβ peptide during its cleavage by γ-secretase. The rationale of BACE inhibition is that it represents an upstream interference with the amyloid cascade, regardless of which species or aggregation states of Aβ then exert toxicity in the brain. 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. 

Developed by Novartis, CNP520 is being jointly developed with Amgen (see company press release). CNP520 is formulated to be taken as capsules.

At the 2016 AAIC conference in Toronto, preclinical data presentations reported significant selectivity of CNP520 for BACE 1 over BACE2 and other proteases such as renin and cathepsin, as well as absence of skin discoloration seen with some prior BACE inhibitors (see Aug 2016 conference news).


No Phase 1 trials for this compound are listed in; however, at the 2016 AAIC conference, Novartis scientists presented safety, tolerability, and pharmacodynamic data from three Phase 1 trials in a total of 113 healthy volunteers. The presentation also included data on dose-dependent lowering of CSF Aβ40 by up to 95 percent (see Aug 2016 conference news).

From August 2015 to March 2016, Novartis ran a multi-site Phase 2 dose-ranging trial in the Netherlands, Belgium, Germany, the United Kingdom, and the United States. It evaluated safety and tolerability, as well as plasma and CSF pharmacokinetics and pharmacodynamics of 1 mg, 10 mg, 25 mg, and 75 mg of CNP520 or placebo administered once daily for 13 weeks to 125 healthy men and women between 60 and 80 years of age. The trial measured change in Aβ38, 40, and 42.

In November 2015, a secondary prevention trial called GENERATION started enrolling 1,340 cognitively normal, homozygous ApoE4 carriers age 60 to 75. As part of the Alzheimer's Prevention Initiative (API) in partnership with Banner Alzheimer's Institute, this Phase 2/3 study is set to run until 2023. The treatment period is five years. This study will randomize half of participants to compare once-daily CNP250 to matching placebo, the other half to compare quarterly injections of the investigational active immunotherapy CAD106 to placebo. The trial will measure the agents' ability to delay diagnosis to MCI or AD dementia and change on the APICC cognitive composite (Langbaum et al., 2015). An extensive list of secondary outcomes include change on the Clinical Dementia Rating Scale sum of boxes (CDR-SB) and other cognitive/functional scales, fluid biomarkers including CSF Aβ and tau, brain imaging including volumetric MRI plus amyloid PET and tau PET measurement of brain amyloid and tangle deposition, respectively, as well as safety measures and Aβ titers (see Jul 2014 conference news).

For all trials of this compound, see and EU Clinical Trials Register.

Clinical Trial Timeline

  • Phase 2
  • Phase 2/3
  • Study completed / Planned end date
  • Planned end date unavailable
  • Study aborted
Sponsor Clinical Trial 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 2026 2027 2028
Novartis Pharmaceuticals Corporation NCT02576639
Novartis Pharmaceuticals Corporation NCT02565511


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News Citations

  1. New Ways to Target Aβ and BACE Show Promising Phase 1 Data
  2. Novartis to Partner with Banner Health on ApoE4 Prevention Trial

Therapeutics Citations

  1. CAD106

Paper Citations

  1. . Establishing Composite Cognitive Endpoints for Use in Preclinical Alzheimer's Disease Trials. J Prev Alzheimers Dis. 2015 Mar;2(1):2-3. PubMed.

External Citations

  2. EU Clinical Trials Register
  3. 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.