Merck & Co has said it can move ahead with large-scale trials of its Alzheimer’s disease treatment MK-8931, now that an independent monitoring board has completed its review of mid-stage data.
MK-8931 is an inhibitor of beta amyloid precursor protein site-cleaving enzyme (BACE), also known as beta secretase, and is designed to interfere with the deposition of the amyloid plaques that are characteristically found in the brains of Alzheimer’s patients.
The 200-patient, phase II/III EPOCH study – which was reviewed by the board – will now be extended into a fully-fledged phase III programme with nearly 2,000 patients with mild-to-moderate Alzheimer’s, said the company. Results are due in the middle of 2017.
Meanwhile, a second phase III trial called APECS, in 1,500 ‘prodromal’ subjects who have mild cognitive symptoms but are not yet considered to have Alzheimer’s, is also about to start. The study will look at two years’ treatment with MK-8931 and will make use of biomarkers to try to gauge its effects, including beta amyloid levels in the brain as well as beta amyloid and tau proteins in the spinal fluid.
The programme balances competing demands in Alzheimer’s testing. There is a recognition that many drugs designed to tackle amyloid plaques once symptoms have already developed – including Lilly’s solanezumab and Pfizer’s bapineuzumab – have struggled to show an effect in trials.
On the other hand, studies in asymptomatic but high-risk populations can take many years to show any impact, so the study in prodromal subjects could help regulators arrive at a verdict on the drug sooner.
MK-8931 is now in the lead in the BACE inhibitor category, after main rival Lilly stopped a phase II trial of its rival candidate LY2886721 in June on safety concerns.
However, the risk that BACE inhibition could cause unexpected side effects is still a big question mark against the class. For example, while mice engineered to have no BACE function are ostensibly fine, they do seem more prone to syndromes resembling schizophrenia and epilepsy.
Meanwhile, other companies active in this area include Eisai with E2609, Roche with RG7129 and AstraZeneca with AZD3293, all of which are in early-stage testing.
“Studies to evaluate potential new treatment options are critical as the global health and financial burden of Alzheimer’s grows,” commented David Michelson, vice president for neuroscience at Merck Research Laboratories.