Second Alzheimer’s Drug Disappoints in Trials
Our primary care doctors in Delray Beach regret to report that for the second time in under two years, a promising drug treatment for Alzheimer’s disease has come up short.
Genentech, a division of drug maker Roche, reported this month that the treatment they’d hoped would slow the progression of Alzheimer’s—called gantenerumab—did not meet their goal of slowing clinical decline in people with early Alzheimer’s disease.
But other studies provide hope.
Genentech conducted two global, placebo-controlled clinical trials on nearly 2,000 patients over 27 months. Half the subjects received a placebo and half received the treatment, a monoclonal antibody.
Gantenerumab is designed to remove clumps of an amyloid beta protein, believed to be responsible for causing Alzheimer’s disease. This sticky compound is thought to damage communication between the cells affect memory, and eventually kill them.
The two studies showed that some patients experienced a slowing of cognitive decline, but not enough to be statistically significant. The company said that the drug did not achieve the main goal of preserving abilities such as remembering, solving problems, orientation, and personal care in patients suffering from early-stage Alzheimer’s disease.
The company’s statement said the treatment removed less amyloid beta than researchers had hoped.
In addition, Genentech reported that 25 percent of those who received the drug experienced a side effect that can cause brain swelling and bleeding.
As we told you last year, another drug called aducanumab (trade name Adulhelm), designed to remove beta amyloid proteins in those with early-stage Alzheimer’s disease, also failed to slow cognitive decline. Nevertheless, the U.S. Food and Drug Administration (FDA) approved this extremely expensive drug over the objections of some critics.
In fact, three members of the FDA advisory panel that had been reviewing the drug took the unprecedented step of resigning in protest after the drug’s approval.
One of them, David S. Knopman, a neurologist at the Mayo Clinic, called the approval process a “sham.” In his resignation to the FDA, he wrote: “Biomarker justification for approval in the absence of consistent clinical benefit after 18 months of treatment is indefensible.”
Translated, he meant that, in his opinion, there is little evidence that reducing beta amyloids (also known as a “biomarker”) slows mental decline. And earlier this year, Medicare refused to provide broad coverage for the drug.
The Alzheimer’s Association, however, still believes this approach shows the most promise for slowing the progression of the disease.
“Although the drug [gantenerumab] did not meet its primary endpoint, the trials further illustrate the relationship between the removal of beta-amyloid and reduction of clinical decline,” the association said in a statement this month.
What Can Help
Another drug, lecanemab, from Japanese drug maker Eisai and its American partner, Biogen, has shown more promise in early trials, slowing cognitive decline by 27 percent. These companies also produced Adulhelm. The FDA is expected to rule on lecanemab by January 6, 2023.
Meanwhile, three new studies have shown that non-drug approaches to slowing cognitive decline hold much more hope for preventing Alzheimer’s.
A large study from Denmark, published in September’s issue of JAMA Neurology, examined the health records of nearly 79,000 men and women over seven years.
The researchers found that those who averaged about 9,800 steps a day (about five miles) were half as likely to develop dementia as sedentary people. The research showed a risk reduction of 25 percent even in those who walked half that amount. And it seems faster is better.
“If you walk about 10,000 steps, your risk [of developing dementia] drops 50 percent,” Borja del Pozo Cruz, who led the new study, told The Washington Post.
“But if 30 minutes of that time is done briskly, you can achieve an extra 10-15 percent risk reduction,” he said.
Another study released in August found that simple stretching, balance, and range of motion exercises worked as well as regular aerobic exercises in slowing the progression of mild cognitive impairment (MCI).
The study, presented at the 2022 Alzheimer’s Association International Conference in San Diego, involved 296 participants who were completely sedentary at the beginning of the study.
At the end of the yearlong study, neither those who performed aerobic workouts or those who did the less demanding exercise experienced any further cognitive decline; those in the sedentary control group did decline further.
Use your Brain, too
Finally, a third study released this month in the journal NEJM Evidence, found that the brain workout provided by regularly attempting to solve crossword puzzles beats computerized brain exercises in slowing cognitive decline in those with MCI.
While earlier studies have shown little benefit to working crossword puzzles, study co-author Murali Doraiswamy, a professor at Duke University, told The Post that in key measurements—cognitive decline scores, functional skills, and changes in brain volume—their results were clear.
“So if you have a mild cognitive impairment, which is different from normal aging, then the recommendation would be to keep your brain active with crossword puzzles,” he said.
Experts say that a combination of regular exercise and challenging mental tasks is key to maintaining brain health. And don’t just focus on crossword puzzles.
“If you’re very good at crossword puzzles and you keep doing only that, you’re still in your zone of comfort and you don’t adopt new strategies, new brain networks,” Sylvie Belleville, a professor of neuropsychology at the University of Montreal, told the paper.