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 studies.
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 inhibitors.
"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," Schoepp said.
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 longer.
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 the disease.
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.
(Reporting by Ransdell Pierson; Editing by Chizu Nomiyama, Dan Grebler and Leslie Adler)