A plaque-busting antibody being tested by Biogen stands a chance to become the first real treatment for Alzheimer’s and could settle a long-running debate over the true cause of the disease.
Biogen’s drug, called aducanumab, was given to 165 patients, and the company says in those who took the highest dose it practically eradicated the amyloid plaques in their brains. Those plaques are widely thought to be what kills nerve cells and causes memory loss.
No effective drug for Alzheimer’s has ever reached the market and scores have failed in testing, so stakes couldn’t be higher. Biogen has estimated that testing aducanumab could cost $2.5 billion, but if it works, it would be hugely profitable and essentially transform what it means to get old for many people.
Biogen’s chief medical officer, Alfred Sandrock, said in a teleconference with journalists that his biggest hope is the drug could be used widely and preventively, as cholesterol-lowering statins are used to ward off heart attacks. “The question will be, can you treat people even earlier?” says Sandrock. “You could treat people before they have symptoms.”
The Boston biotech company is reporting the results of a pilot study today in Nature, but two larger Phase III studies, involving 2,700 volunteers, are already under way and will determine whether the drug not only clears plaques but also prevents memory loss and death. Sandrock said Biogen’s data so far offer “hints” that the drug does slow the progression of the disease.
“I would have to say the data are pretty exciting,” says James Leverenz, director of the Lou Ruvo Center for Brain Health at the Cleveland Clinic. Along with other doctors, he began learning about the Biogen data last year, when the company began talking it up at meetings and arranged for his center to participate in the larger study. His center has contributed five patients so far.
“When we all saw this, a lot of us said ‘Gee, this seems almost too good to be true,’” says Leverenz. “So I wanted to join the Phase III data before I jump on the boat.”
Biogen is selecting patients at the earliest stage of the disease, when the plaque-busting drug is expected to help the most. Patients are chosen who have plaques in their brains but few symptoms as yet. The idea is to prevent the disease, since once brain cells are dead, the drug won’t help.
The decay of memory in Alzheimer’s is different from the memory loss that most people experience as they age. “Normal aging is difficulty pulling up information,” says Leverenz. “You can’t pull up a name. But five minutes later you can. The information is in there.” But Alzheimer’s is characterized by the inability to form new memories. Its onset is often first observed by family members. A husband notices that his wife can’t remember they had friends over for dinner last week; a daughter returning home for a visit finds that her father doesn’t know her.
If the Biogen drug works, it will also basically prove the “amyloid hypothesis,” the dominant theory that Alzheimer’s is caused by the buildup of a peptide called amyloid beta as plaques on brain tissue. The drug sticks directly to the plaques and probably recruits scavenger cells called microglia to arrive and remove them.
“What they showed very nicely was a reduction in plaques as they increased the dose. This is the most significant part of the study, and it looks very convincing,” says Steven Paul, who is CEO of Voyager Therapeutics, a gene-therapy company, and previously co-invented a different anti-Alzheimer’s antibody currently being tested by Eli Lilly. Paul says Biogen’s drug is the first to break up plaques in this way.
If the drug doesn’t help patients, however, scientists might have to fundamentally reconsider their approach. Some maintain that the plaques are a side effect of the disease and not its cause.
The drug did have worrying side effects. It caused brain swelling in some patients and caused them to drop out of the trial. That could limit how widely the drug is used if it ever reaches the market.
The implications of a drug that slows Alzheimer’s are difficult to overstate. Paul says if the progression of the disease could be delayed by five years, it would cut by half the number of people who suffer from it (people would die from other causes). By some estimates, caring for Alzheimer’s patients in the U.S. will cost a staggering $1 trillion per year by 2050.