Positive results in phase Ib study in patients with Alzheimer’s disease
Merck & Co has presented positive clinical results with its BACE inhibitor for Alzheimer's disease, cementing its lead in the race to bring the drugs to market.
The data was early stage - coming from a phase Ib study - but confirmed that MK-8931 reduced cerebrospinal fluid (CSF) levels of beta amyloid in patients with mild-to-moderate Alzheimer's disease.
BACE or beta-secretase is an enzyme involved in the conversion of amyloid precursor protein (APP) into amyloid beta, which is deposited as plaques in the brains of patients with Alzheimer's disease. Inhibitors of BACE are designed to interrupt this process, prevent the formation of plaques and - if the amyloid hypothesis of Alzheimer's is correct - block degeneration of neurons in the disease.
Merck had been lagging behind in the race to develop BACE inhibitor but leapfrogged into the lead last month when Lilly stopped a phase II trial of its rival candidate LY2886721 after some patients experienced abnormal liver function tests suggesting the drug may be unsafe.
Data from a phase Ib trial of MK-8931 in healthy volunteers was reported last year, and the latest results build on that to show that the drug also exerts its anti-amyloid effect in patients with established Alzheimer's dementia.
Merck has also started a larger phase II/III study of MK-8931 in around 200 Alzheimer's patients - called EPOCH - that could be expanded into pivotal trial if early safety and efficacy objectives are met.
Greater interest has been paid to BACE inhibitors since other amyloid-targeting therapies - notably Pfizer & Johnson & Johnson's bapineuzumab and Lilly's solanezumab - failed to show significant benefits in phase III trials reported last year.
These drugs tried to break down plaques that were already formed, and the hope is that by targeting amyloid further upstream with BACE inhibitors and other anti-amyloid therapies the effects of treatment will be improved.
Other BACE inhibitors coming through the clinical pipeline for Alzheimer's disease include Eisai's E2609, Roche's RG7129 and AstraZeneca's AZD3293, all of which are in early-stage testing.
Meanwhile Lilly has confirmed it will carry out a third phase III trial of solanezumab in 2,100 early-stage Alzheimer's patients, including people with amyloid in their brans but no overt signs of dementia.