Merck releases positive clinical trial data for Alzheimer’s disease drug candidate

July 16 2013 | By Márcio Barra

Merck released this Sunday results from a Phase Ib study of its experimental Alzheimer’s disease (AD) drug MK-8931, in patients with mild to moderate AD, with the drug achieving positive results in reducing the level of β amyloid proteins.

MK-8931 is an oral BACE (β-site amyloid precursor protein cleaving enzyme) inhibitor. BACE is the first protease to process the amyloid precursor that eventually produces β amyloid in the brain. It is assumed that an excess level of amyloid-β in the brain over a long time period is a leading factor in the pathogenesis of AD, and as such treatments that either directly target β amyloid or its precursors are one of the leading treatment hypotheses despite Bapineuzumab’s 2012 failure, alongside Tau protein.
The data from the randomized, double-blind, placebo controlled study showed that administration of MK-8931 at doses of 12, 40 and 60 mg resulted in a dose-dependent and sustained reduction in the levels of Ab40, a measure of BACE1 activity. Ab42 and sAPPβ levels were also measured.

This gives Merck a lead against other company who are also developing BACE inhibitors, like AstraZeneca and Eli Lilly. The latter recently terminated a Phase II study for LY2886721, due to abnormal liver biochemical tests in patients. In the press release, Lilly stated it believes that the abnormal liver biochemical tests observed in the study weren’t related to BACE inhibition. It’s worth noting that Merck’s MK-8931 candidate showed no serious adverse events or study discontinuations due to adverse events during the phase Ib study.

“The amyloid β reduction observed with MK-8931 may offer an opportunity to further understand the role BACE1 inhibition plays in the underlying pathology of Alzheimer’s disease,” said Darryle Schoepp, Ph.D., vice president of Neuroscience Early Development and Discovery Sciences, Merck. “Further evaluation of MK-8931 continues in our EPOCH study, a Phase II/III trial in patients with mild to moderate Alzheimer’s.”

The mentioned EPOCH study is the next step for Merck, with 200 patients being recruited for this phase II/ III study. Meanwhile, Merck is continuing to develop other BACE inhibitor candidates.

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