New drug reduces Alzheimer’s protein levels in clinical trial

Posted on 2nd November 2016

Science Translational Medicine: The BACE1 inhibitor verubecestat (MK-8931) reduces CNS β-amyloid in animal models and in Alzheimer’s disease patients

In results from a phase 1 clinical trial published today (Wednesday 2 November), a potential new drug called verubecestat has been shown to reduce levels of the Alzheimer’s protein amyloid in brain and spinal fluid in people with Alzheimer’s disease. The results are published in Science Translational Medicine.

Verubecestat is a drug that blocks or ‘inhibits’ the action of a protein called BACE1, which processes amyloid into a toxic form that builds up in the brains of people with Alzheimer’s. It is the first BACE1 inhibitor to reach phase 3 clinical trials, with the development of other BACE1 inhibitors halted previously due to the serious side effects experienced by people taking the drugs. The study published today is a phase 1 trial of verubecestat in which researchers tested different doses to see whether the drug was safe and well-tolerated in animals, as well as people with mild to moderate Alzheimer’s disease.

Over the course of 7 days, 32 people with mild-to-moderate Alzheimer’s took a daily pill containing either 0, 12, 40 or 60 mg verubecestat.  The level of amyloid was measured in the fluid surrounding their brain and spinal cord, called cerebrospinal fluid. The researchers found that verubecestat reduced the level of amyloid in the participant’s cerebrospinal fluid, with the greatest effect seen with the highest dose of 60 mg. They also reported that the serious side effects previously seen in studies with other BACE1 inhibitors, such as liver damage, were not observed in people treated with verubecestat.

These findings support the continued clinical development of verubecestat, which is currently being tested in two further clinical studies that have both recently completed recruitment. A phase 2/3 study in people with mild to moderate Alzheimer’s is due to end in summer 2017 and a phase 3 study testing the drug in very early Alzheimer’s is due to finish in early 2018. These studies are testing verubecestat in a much larger number of people to see whether the drug can slow the decline in memory and thinking skills in people with the disease.

Dr Rosa Sancho, Head of Research at Alzheimer’s Research UK, said:

“It has been over a decade since a new drug was licenced for the treatment of dementia, so we urgently need new medicines that can provide real benefit for people living with dementia. There is a wave of potential new treatments currently being tested for dementia, with the results of these studies hotly anticipated over the course of the coming months and years. In this small phase 1 clinical trial, verubecestat was able to reduce the levels of a key Alzheimer’s protein, but it remains to be seen whether this translates into slower memory decline for people with the disease.

“As verubecestat works differently to other drugs currently being tested for Alzheimer’s, if it proves successful, it could be an important weapon in the arsenal for doctors treating the disease in future. Alzheimer’s is a complex and devastating disease and so a multi-pronged approach may give us the best chance of tackling it in the coming years. As the first BACE1 inhibitor to reach the final stages of testing in people, the ultimate test will be whether these ongoing trials show verubecestat can provide tangible benefits for people with Alzheimer’s. Scientists have reflected on past lessons in Alzheimer’s drug development and it is promising to see an increasing number of drugs now entering phase 3 clinical testing in the disease, giving us renewed hope in the hunt for new treatments.”

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