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• Posted August 17, 2023

Most Alzheimer's Patients May Be Ineligible for Newly Approved Drugs

Two recently approved treatments offer newfound hope for patients in the early stages of Alzheimer's disease, but most people who could benefit will likely be deemed ineligible, a new study finds.

Alzheimer's affects about 6.7 million Americans age 65 and older. But only about 8% to 17% of older adults with early signs of the disease meet the eligibility criteria as determined by clinical trials for the drugs, Leqembi and Aduhelm, researchers say.

The vast majority would be disqualified because of chronic health conditions and brain scan abnormalities common in older adults.

Leqembi and Aduhelm are monoclonal antibody treatments. Because of the tremendous need for Alzheimer's treatments, they received accelerated approval by the U.S. Food and Drug Administration, with Leqembi (lecanemab) given traditional FDA approval in July.

“Understandably, there's wide interest in new and emerging treatment options for Alzheimer's disease. Prior to recently, we hadn't had a new approved drug for Alzheimer's disease in more than 20 years, and it's a devastating disease,” said study co-author Dr. Vijay Ramanan, an assistant professor of neurology at the Mayo Clinic in Rochester, Minn.

These new medications are a good step forward, Ramanan said.

Leqembi was shown in clinical trials to delay progression of Alzheimer's disease.

“One of the big challenges that's facing the field is to translate what we have learned from the clinical trials to real world practice," Ramanan said.

That's what this study worked to do, using 237 people in the Mayo Clinic Study of Aging, ages 50 to 90. All had mild cognitive impairment or mild dementia, and their brains showed increased amounts of amyloid-ß plaques, hallmarks of Alzheimer's disease.

Using specific inclusion criteria -- body mass index and scores on thinking and memory tests -- researchers found about 47% of these individuals would meet qualifying criteria.

But then they looked at other clinical trial exclusions, which included stroke, heart disease, a history of cancer, or signs of small brain bleeds or injuries on brain scans.

When those were factored in, the researchers discovered only 8% of the study participants would have been eligible for the Leqembi trial.

Without the thinking and memory tests, 17% of those with mild cognitive impairment would have been eligible.

For Aduhelm (aducanumab), 44% of participants would have met the required characteristics, but after excluding for certain health issues, just 5% would have been eligible.

“Clinical trials are not perfect, but they do provide an initial evidence base for use of diagnostics and treatments,” Ramanan said.

He noted a consensus that's building in the field -- that appropriate use of medications should in many ways mirror the conditions under which the drug was tested in clinical trials.

“Understanding how well those criteria actually apply to the general population is important information to be able to counsel both clinicians and patients appropriately on what they can expect,” Ramanan said.

The study offers very important information for clinicians, that a lot of the people who may seem eligible or may request treatment will not really be appropriate candidates for treatment, said Dr. Stephen Salloway, founding director of the Memory and Aging Program at Butler Hospital in Providence, R.I.

Salloway is co-author of an editorial accompanying the study findings. Both were published Aug. 16 in the journal Neurology.

Among the exclusions, Salloway noted that there is no evidence Leqembi works for people in the later stages of Alzheimer's disease.

“It's hard to say no to patients, but it's very important not to offer a treatment that has some significant risks when there's not much chance of benefit,” Salloway said.

In rare cases, Leqembi was linked to brain bleeds. It's also very expensive at $26,500 per year.

Even with the limitations, these new medications are important because there are very limited treatment options for this major disease, Salloway said.

“It's disabling. It's almost always fatal," he said. "People live a long time with it. It's very costly. It's burdensome for the family. So anything that helps is good."

However, "these treatments, to be realistic, only have mild benefits," Salloway said. Yet they open a new treatment era for this disease, he added.

“Alzheimer's will increasingly become a treatable disease that we need to respond to like we do for heart disease or cancer,” Salloway said.

As for the current study, "the main takeaway is that patients and families should talk to their family doctor if they're concerned about memory loss and get it evaluated, first and foremost. And then they could be a candidate if they have early Alzheimer's and don't have any exclusions,” Salloway said. “And then clinicians just have to be careful, selecting appropriate patients and then monitoring them."

A study limitation is that the participants were mostly white. More research in large, diverse populations is needed, the authors said.

The study was supported by numerous organizations, including the U.S. National Institutes of Health.

More information

HealthDay's wellness library has more on the stages of Alzheimer's disease.

SOURCES: Vijay Ramanan, MD, PhD, neurologist and assistant professor, neurology, Mayo Clinic, Rochester, Minn.; Stephen Salloway, MD, founding director, Memory and Aging Program, Butler Hospital, and professor, psychiatry and human behavior and neurology, Warren Alpert Medical School of Brown University, Providence, R.I.; Neurology, Aug. 16, 2023