Alzheimer's researchers have almost gotten used to having their hopes dashed when a promising drug fails to live up to its potential in clinical trials. But now a new therapy is injecting fresh optimism into the field, and the results are prompting scientists to say it's the best news they've seen for treating this deadly disease in 25 years.
The drug, developed and tested by biotech firm Biogen, is called aducanumab. In its clinical trial, the drug helped to erase beta amyloid, a sticky plaque that builds up in the brain and can lead to the symptoms of Alzheimer's disease. The results of phase one of the study were reported in the journal Nature last month and included 165 patients with early stage Alzheimer's. Patients with this level of the disease typically have trouble remembering conversations, using things around the house or concentrating, but can otherwise function on their own. The truly devastating part of Alzheimer's is that these symptoms almost always continue to worsen.
Biogen's phase one trial showed that those receiving the highest doses of aducanumab every month over the course of a year saw the greatest decrease in the amount of amyloid plaque in their brains. Researchers were able to view this change through the use of a high-powered imaging tool known as a brain PET (positron emission tomography) scan. But what really has scientists excited this time around is the degree to which the worsening of memory loss slowed in patients taking the drug.
"This is the first antibody tested where the people who had the greatest removal of amyloid from their brains also saw the greatest stabilization of their clinical decline," said Dr. Adam Boxer, professor of neurology at the Memory and Aging Center at the University of California, San Francisco. "That's the impressive part."
Researchers say if further clinical testing yields the same or better results, the drug could be approved and on the market within five years.
Aducanumab isn't the only drug designed to erase amyloid in the brain. Drug maker Eli Lily is currently in phase three trials with a drug called solanezumab, which also seeks to bind to amyloid and remove it from the brain. Although scientists are quick to point out that neither drug has proved to be a definitive success yet, they each have strengthened belief in what's known as the amyloid hypothesis: the theory that states the reduction of amyloid in the brain can slow the progression of Alzheimer's.
The idea that a drug could clear the brain of amyloid and halt the progression of memory loss is beyond anything doctors have at their disposal today. The FDA-approved drugs now on the market and most widely prescribed to treat Alzheimer's — Aricept and Namenda — are helpful but limited, physicians say. They treat only symptoms of the disease and give patients anywhere from six to 12 months of mild improvement.
Even the latest drug to be granted approval for Alzheimer's — Namzaric — is basically a combination of two existing drugs and claims only to slow the worsening of symptoms for a while. Like Aricept and Namenda, Namzaric has no effect on stopping or preventing the underlying disease.
That's why researchers and pharmaceutical companies are increasingly turning their focus to disease-modifying prevention drugs. If drugs like aducanumab and solanezumab can potentially slow Alzheimer's symptoms from worsening, newer therapies being worked on today are aimed at stopping them before they even start.
The hope is that by treating people at risk for Alzheimer's before symptoms appear, we can potentially prevent or even delay the onset of memory loss and other markers of the disease. Researchers at the Washington, D.C.-based advocacy group UsAgainstAlzheimer's liken this prevention-centric approach to the treatment of patients that are HIV positive. The drugs available today help these patients from ever developing AIDS symptoms.
"We want to run out the clock with Alzheimer's," said James Hendrix, director of global science initiatives at the Alzheimer's Association. "The disease most commonly strikes people over the age of 65, so if we could delay the onset of the worst of the symptoms long enough, people will die of something else. But when they do die, they will do so with their memories intact."
To truly understand just how catastrophic an illness such as Alzheimer's is, consider that it is the only cause of death among the top 10 in the United States that can't yet be prevented, cured or even slowed. According to the Alzheimer's Association, there are now 5.3 million Americans age 65 and older living with the disease. Currently, 1 in 3 seniors dies with Alzheimer's or dementia. The total direct cost to the U.S. economy of caring for those with Alzheimer's: a staggering $236 billion, with half being borne by Medicare.
Delaying the onset of the disease by just five years, research studies show, could decrease Medicare spending by 50 percent. That's an important point to consider, because economists forecast that unless something is done to cure or even slow the symptoms, the number of people with Alzheimer's will rise to 16 million by 2050 and cost the U.S. economy $1.1 trillion. The portion covered by Medicare will balloon to $589 billion.
As optimistic as researchers have been with news of aducanumab's results, there's still much that's unknown. Certain side effects, including brain swelling — and in some cases brain bleeding — were seen in patients taking the highest doses of the drug. It's hard to draw conclusions about safety and efficacy from the small number of people in the phase one trial, said Dr. Boxer.
That's why Biogen began two new large-scale phase three clinical studies of the drug in August that will now include 2,700 patients worldwide with early stage Alzheimer's. These folks will be given the drug (or a placebo) for 18 months — longer than in the phase one trial. And like the earlier study, the primary objective of this new trial is to evaluate how effective monthly doses of aducanumab is in slowing cognitive and functional impairment for these patients. "If the risk/benefit ratio is not favorable [in the next trial], that would dampen people's enthusiasm," said Dr. Boxer, "especially if the drug were to be used preventatively in people that are asymptomatic."
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Still, there's reason to be hopeful, scientists believe. "I think the efficacy of this drug in clearing [amyloid] plaque is very significant for patients with Alzheimer's," said Dr. Marc Diamond, founding director of the Center for Alzheimer's and Neurodegenerative Diseases at the University of Texas Southwestern.
Adds Dr. Boxer: "If the same or very similar results are obtained [with phase three], then that would be even more exciting. That would suggest that this drug really works." And that's the best news Alzheimer's patients have had in a long time.
— By Susan Caminiti, special to CNBC.com