Elenbecestat (formerly E2609) is an oral therapy that Eisai and Biogen are developing to delay the start of early-stage Alzheimer’s disease and perhaps stop its progression.

How elenbecestat works

Alzheimer’s disease is characterized by a build-up of beta-amyloid plaques in the brain, which damages nerve cells. The plaques are formed when the beta-amyloid cleaving enzyme, or BACE1, cuts the “parent” beta-amyloid protein into pieces. This parent protein is known as the amyloid precursor protein or APP.

Elenbecestat is a BACE1 inhibitor. It is designed to reduce beta-amyloid plaque formation by preventing the BACE1 enzyme from cutting up APP.

Elenbecestat in clinical trials

Studies in animals showed that elenbecestat can lower beta-amyloid levels in the brain, the cerebrospinal fluid that envelops the brain and spinal cord, and the blood.

Eisai and Biogen have conducted nine Phase 1 clinical trials of elenbecestat, eight of which were completed by March 2015.

The first two trials showed that participants could tolerate doses of up to 200 mg of elenbecestat, with dizziness and headaches being the most common side effects.

A Phase 2 trial (NCT02322021) that began in November 2014 investigated whether elenbecestat was safe and could slow the progression of Alzheimer’s disease in 70 patients with mild cognitive impairment, or mild to moderate dementia. During the trial, patients receive either a placebo or 5, 15, or 50 mg of elenbecestat in single daily doses over 18 months. Eisai reported that no serious adverse reactions were noted in any of the treatment arms. The 50 mg elenbecestat group also showed significantly reduced levels of beta-amyloid compared to the placebo group.

Eisai and Biogen started two Phase 3 trials in 2016 called MISSION AD1 (NCT02956486) and MISSION AD2 (NCT03036280). The main goal of the studies is to further investigate the effectiveness of the 50 mg dose of elenbecestat. 

The plan is for 1,330 patients to receive 50 mg of elenbecestat daily for two years. There are multiple measures of effectiveness: whether the treatment can reduce the severity of dementia symptoms; if it can lower beta-amyloid levels in the brain; whether it can prevent deterioration of the hippocampus, a brain region that Alzheimer’s disease has a major effect on; and whether it can reduce levels of Alzheimer’s disease biomarkers in the cerebrospinal fluid.

Both trials are still recruiting participants in the U.S.; see link here. MISSION AD2 also is scheduled to be held in Japan. In addition, Eisai and Biogen have asked European regulators to approve trials there.

Eisai also announced that elenbecestat was selected by the Alzheimer’s Clinical Trial Consortium (ACTC) to be included in a new clinical trial targeting primary prevention of Alzheimer’s disease, called A3, which should begin in 2020.

Other details

Eisai announced in 2016 that the U.S. Food and Drug Administration had granted fast-track status to elenbecestat. Fast track status is aimed at accelerating the development and regulatory review of treatments for serious conditions and that fill an unmet need.


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.

Victoria Tan BNS Writer
Victoria Tan BNS Writer