By Ransdell Pierson
Dec 10 Merck & Co said it will begin two
late-stage trials of its experimental Alzheimer's drug, one of
the industry's best hopes for slowing the memory-robbing
disease, after an independent monitoring board reviewed its
safety and recommended that more patients be recruited for
The data monitoring committee gave its blessing to a Phase
III trial involving up to 1,960 patients after examining interim
safety data from a mid-stage trial of 200 patients who had been
treated with the medicine, called MK-8931, for at least three
months. The planned new study, called EPOCH, is expected to
conclude in mid-2017, Merck said on Tuesday.
The medicine works by blocking an enzyme called beta
secretase that is involved in production of beta-amyloid, a
protein that creates brain plaques considered a major cause of
the progressive disease. Such medicines are known as BACE
"There's good reason to hope that a BACE inhibitor might
help patients, and ours is the first to get the go-ahead for
Phase III" trials, Darryle Schoepp, head of neuroscience at
Merck, said in an interview.
Merck will also begin a separate Phase III trial of the
drug, involving 1,500 patients, in "prodromal" patients who do
not yet have dementia.
That study, called APECS, will enroll patients with mild
cognitive problems and potential biomarkers for Alzheimer's,
such as elevated levels of beta amyloid in the brain and of beta
amyloid and the protein tau in spinal fluid. They will be
treated for two years.
The trial is predicated on the theory that early
intervention may be crucial, and that once dementia develops it
may be too late to seriously arrest Alzheimer's disease.
"The prodromal trial is exciting because it may teach us
whether we can prevent or slow down the onset of dementia,"
An estimated 5 million Americans have Alzheimer's, the most
common cause of dementia. More than 38 million people worldwide
are believed to have dementia, including Alzheimer's disease,
and those numbers are expected to rise as more people live
Unlike heart disease and cancer, no major advancements have
been seen in Alzheimer's drug research since the first treatment
was approved in 1993 by U.S. regulators.
Current Alzheimer's drugs, including Namenda from Forest
Laboratories Inc and generic forms of Pfizer Inc's
Aricept (donepezil), can minimally and briefly help
memory and ability to perform daily functions, but do not slow
Oral drugs to block beta secretase have taken center stage
after an injectable class of medicines, meant to remove beta
amyloid plaque after it has already formed, failed or fell short
last year in trials conducted by Pfizer Inc and Eli
Lilly and Co.
Safety of the new drugs became a major concern in June, when
Lilly pulled the plug on its own BACE inhibitor due to liver
toxicity. Merck, Johnson & Johnson, Roche Holding AG
and Eisai Co Ltd are still in the race.
Although data from Merck's mid-stage trial of MK-8931
remains blinded, or secret, the data monitoring committee was
allowed to examine the data for hints of safety issues. Its
green light could help ease safety concerns over the emerging
new class of medicines.
The Merck drug in earlier trials cut production of a-beta
peptide, the building block of beta amyloid plaque, by 79
percent, Schoepp said.
"You're turning off the faucet, shutting at its source the
pathway that forms a-beta peptide," said Schoepp. The toxic
peptides clump together to form beta amyloid plaques in the
brain that are a hallmark of the disease.
J.P.Morgan analyst Chris Schott said expectations remained
"low" for BACE inhibitors following the termination of Lilly's
product. But he said Merck's drug could generate annual sales of
more than $5 billion if it succeeds in trials and is approved.
Merck shares slipped 0.4 percent to $49.35 in afternoon
trading on the New York Stock Exchange, amid moderate declines
for the drug sector.