Atabecestat (Formerly JNJ-54861911)

Atabecestat (formerly JNJ-54861911) was an experimental treatment for Alzheimer’s disease that Janssen Pharmaceuticals was developing. However, the company decided to discontinue the development of atabecestat after elevated liver enzyme levels were discovered in some clinical trial participants.

Scientists think that the clumping of harmful beta-amyloid protein in the brain plays a key role in the development of Alzheimer’s disease. Atabecestat was aimed at preventing this clumping.

How atabecestat works

The process that leads to beta-amyloid clumping starts when an enzyme cuts amyloid precursor protein (APP) into short fragments of beta-amyloid. The enzyme is called beta-amyloid cleaving enzyme 1, or BACE1.

Atabecestat inhibits BACE1. Janssen hoped that preventing the enzyme from generating beta-amyloid would head off the formation of toxic protein clumps in the brain.

Atabecestat in clinical trials

A number of clinical trials have investigated atabecestat’s safety, tolerability, and effectiveness. 

A Phase 1 study (NCT01887535) that began in 2013 investigated whether the treatment was safe and tolerated in healthy older people. The participants were divided into five groups, each receiving a different dose of atabecestat. A key measure of effectiveness was whether atabecestat could lower beta-amyloid levels in the cerebrospinal fluid that bathes the brain and spinal cord. Janssen discovered that it did, and the results of the study were presented at the 12th International Conference on Alzheimer’s and Parkinson’s Diseases in 2015.

Another Phase 1 trial (NCT02360657) evaluated atabecestat’s ability to lower beta-amyloid levels in the cerebrospinal fluid of people at risk of developing Alzheimer’s disease but who had no symptoms. It also assessed the treatment’s safety and tolerability. Researchers randomly assigned patients to one of three groups. Those in the first group received 10 mg of atabecestat once a day for up to four weeks, those in the second group received 50 mg of atabecestat, and those in the third group received a placebo. The study has been completed, but no results have been published.

A Phase 2 trial (NCT02406027) was evaluating whether atabecestat is safe in patients with early Alzheimer’s disease. Researchers enrolled patients who had completed Phase 1b or Phase 2 clinical trials of atabecestat and wanted to continue treatment.

Janssen also conducted a placebo-controlled Phase 2b/3 trial (NCT02569398), called EARLY, comparing atabecestat’s ability to slow cognitive decline in 596 people who were at risk of developing Alzheimer’s disease but had no symptoms.

Both the long-term Phase 2 trial and the Phase 2b/3 trial were stopped after elevated liver enzyme levels were observed in some study participants. Based on these results, Janssen discontinued the development of atabecestat.


Alzheimer’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.