AZD3293 (also known as lanabecestat and LY3314814) is a therapy candidate being developed by AstraZeneca and Eli Lilly for the treatment of early Alzheimer’s disease.

Alzheimer’s disease is the most common cause of dementia, affecting millions of mostly elderly people around the world. Despite decades of research, no cure or even an effective management strategy for this condition are currently available. As the number of people with dementia gradually increases due to increasing life expectancy, the pressure to develop an effective treatment for this neurodegenerative disease continues to grow. AZD3293, if approved, could help slow the progression of Alzheimer’s disease.

How AZD3293 works

The development and progression of Alzheimer’s disease are characterized by a gradual build-up of amyloid plaques in the brain. These plaques consist of insoluble misfolded amyloid-beta protein. This protein and shorter peptides derived from it are toxic to the brain. The formation of plaques involves the action of multiple enzymes, including BACE1. AZD3293 inhibits BACE1 and thus blocks the development of amyloid-beta. It is thought that AZD3293 may, therefore, help prevent the formation of amyloid plaque and thus slow down or even stop the disease’s progression.

AZD3293 in clinical trials

Several Phase 1 trials demonstrated that AZD3293 is well-tolerated across a range of doses and reduced the level of amyloid-beta in the fluid surrounding the brain and spinal cord, as well as in the blood. The effective suppression of amyloid-beta was reported even with once weekly dose of the potential drug.

A multicenter Phase 2/3 clinical trial (NCT02245737) called AMARANTH is comparing two doses of AZD3293 to a placebo given for two years to 2,202 patients with early Alzheimer’s disease. The outcomes will be measured by change in the clinical dementia rating sum of boxes (CDR-SOB), a measure of the severity of dementia in Alzheimer’s disease, compared to the start of the trial. Changes in clinical markers and brain scan results also will be assessed. After positive interim results, AstraZeneca and Eli Lilly announced in April 2016 that the trial will continue to Phase 3. The trial is currently recruiting participants and is set to run until 2019.

A second Phase 3 trial (NCT02783573) called DAYBREAK-ALZ will be conducted in 228 locations around the world and enroll 1,899 patients with mild dementia caused by Alzheimer’s disease. The study will compare two once-daily doses of AZD3293 given for three years to two groups of participants. This trial is currently recruiting participants and is set to run until 2021.

In August 2016, AstraZeneca and Eli Lilly announced that AZD3293 received fast track designation from the U.S. Food and Drug Administration (FDA). The fast track program aims to expedite the development and review of new therapeutics.

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