In August 2016, AstraZeneca and Eli Lilly announced that Lanabecestat received fast-track designation from the U.S. Food and Drug Administration (FDA). This designation facilitates the development and review of therapeutics for serious diseases with high unmet medical need.
How Lanabecestat works
Alzheimer disease is characterized by a gradual build-up of beta-amyloid plaques in the brain. These plaques consist of insoluble misfolded protein fragments that are toxic to the brain. They cause damage to nerve cells, resulting in a decline in memory and the ability to think and learn.
The formation of beta-amyloid plaques involves the action of multiple enzymes, including BACE1 (beta-secretase cleaving enzyme). Lanabecestat works by inhibiting BACE1, blocking the formation of beta-amyloid. In this way, it is thought that Lanabecestat may help prevent the formation of beta-amyloid plaque and slow, or even stop, progression of the disease.
Lanabecestat in clinical trials
Several Phase 1 trials demonstrated that Lanabecestat is well-tolerated across a range of doses and reduced the level of beta-amyloid in the fluid surrounding the brain and spinal cord (cerebrospinal fluid), as well as in the blood. It was reported that the treatment could effectively suppress beta-amyloid with as little as a once-weekly dose.
A multicenter Phase 2/3 clinical trial (NCT02245737) called AMARANTH is comparing two doses of Lanabecestat to a placebo in 2,202 patients with early Alzheimer’s disease. The outcomes will be measured by the 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 ongoing and is set to run until September 2019.
A second Phase 3 trial (NCT02783573) called DAYBREAK-ALZ will be conducted at 228 locations around the world and aims to enroll 1,899 patients with mild dementia caused by Alzheimer’s disease. The study will compare two once-daily doses of Lanabecestat given for three years to two groups of participants. This trial is recruiting participants and is set to run through 2021.
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