Merck & Co. on Tuesday announced that it will end a study of its once-promising Alzheimer’s disease drug in patients with mild-to-moderate forms of the condition, just three months after Eli Lilly and Co. announced its own setback in a field that’s been littered with failures.
There was “virtually no chance of finding a positive clinical effect,” according to an independent panel of experts that looked at the trial partway through. A separate trial of verubecestat in patients who are showing only symptomatic hints of the degenerative disease will continue, Merck said in a written statement, since the panel didn’t find safety signals worrisome enough to also halt that test.
“It’s very disappointing, once again,” said David Knopman, a professor of neurology at the Mayo Clinic in Rochester, Minnesota.
Shares of Kenilworth, New Jersey-based Merck fell less than 1 percent, to $65.24, Wednesday morning.
Alzheimer’s affects about 44 million people worldwide, and robs people of their memories and ability to care for themselves. There hasn’t been a new drug for alleviating symptoms in more than a decade, and there are no medicines proven to slow the condition.
Merck’s drug and others target a plaque, called amyloid, thought to be a cause of the disease. While more such treatments are in development from companies including Biogen Inc. and Roche Holding AG, many researchers now believe that administering drugs after amyloid has built up in the brain may be too late.
Indianapolis-based Lilly's failed drug, solanezumab, took a similar amyloid-blocking approach.
“There is mounting evidence—of which this is another piece—that removing amyloid once people have established dementia is closing the barn door after the cows have left,” Knopman said.
It’s possible that patients in the study were getting the drug too far along in their disease to help. Verubecestat and similar drugs, called BACE inhibitors, operate before the amyloid has formed into plaques. In the Merck study, however, the patients with mild-to-moderate disease would already have buildup.
“You need to go in at the very earliest stage of disease to show the kind of improvement we are hoping for,” said James Hendrix, director of global science initiatives at the Alzheimer’s Association. “BACE isn’t going to do anything about the plaques that are already there. Maybe if you can go in before there is a lot of plaque buildup in the brain, that’s where you will have the most benefit.”
It’s also possible that the drug was too weak, or that not enough of Merck’s drug was making it into the brain, Knopman said. Previous studies have shown that the drug does have a powerful impact on amyloid levels, though doctors and others in the industry will have to wait for more details of the trial to draw any conclusions, he said.
While investors’ expectations for the study known as Epoch were low, analysts estimated the drug would hit peak sales of about $1.3 billion in 2024, said Mark Schoenebaum, an analyst at Evercore ISI in New York. Patients weren’t given imaging tests to ensure they had plaque buildup from Alzheimer’s disease before they started the trial, an issue that has caused problems in rival studies, he said.
“While it remains possible that BACE inhibition may still have a place in Alzheimer’s disease treatment, the failure of this study for futility will dampen investor enthusiasm for the mechanism,” Schoenebaum said.