Merck ($MRK) has posted a roundup of data generated to date on its BACE1 inhibitor in Alzheimer’s disease tests and trials. The package includes results from a seven-day, 32-person trial that linked the drug to lower levels of beta-amyloid peptide 40 and other biomarkers of Alzheimer’s.
In the seven-day Phase Ib trial, details of which were first shared in 2013, Merck randomized patients to receive one of three daily doses of BACE1 inhibitor verubecestat or a placebo. After seven days, Merck looked at the concentrations of beta-amyloid 40 and other amino acids linked to the formation of amyloid plaques. In the cohort that took the highest dose, levels of beta-amyloid fell by as much as 90% over the 24 hours patients were monitored. The time weighted average reductions for the different doses over the period ranged from 57% to 84%.
Whether those declines translate into improvements in cognitive function is a question for a pair of much larger Phase III trials that are due to begin reporting data late next year. Merck is enrolling 1,500 patients with mild cognitive impairment in one study, and has already recruited 2,221 people with mild-to-moderate Alzheimer’s to participate in the other. Those trials are using two different scales to measure the cognitive function of participants.
Merck presented the Phase Ib results in a paper in Science Translational Medicine that also collated data generated in animals and healthy volunteers. Positives from the paper include long-term beta-amyloid reductions in animals, evidence of target engagement and the lack of signs of liver toxicity in either animal or human studies. In 2013, Eli Lilly ($LLY) scrapped a trial of its BACE1 inhibitor after seeing “abnormal liver biochemical tests.” Roche ($RHHBY) dumped a BACE1 drug in 2013, too, without explaining its reasoning.
Those dropouts thinned the BACE1 field. Merck, which gained its BACE1 drug in the Schering Plough deal, is leading the way. Biogen ($BIIB) and Eisai committed to moving their program into Phase III earlier this year. And AstraZeneca ($AZN) and Lilly transitioned to the Phase III part of their Phase II/III trial after coming through an interim safety review unscathed in April.
Each company is hoping BACE1 lives up to its billing as a possible watershed moment in the long and unsuccessful slog to develop Alzheimer’s drugs. The interest in the approach is underpinned by evidence of the role the BACE1 enzyme plays in the production of amyloid beta.