Data from the Mayo Clinic shows limited eligibility for the anti-amyloid treatment. However, Michael Irizarry, Eisai’s deputy chief clinical officer, says some patients could still be eligible.
A scientific analysis of Alzheimer’s disease/istock, digicomphoto
With the FDA’s full approval of Eisai and Biogen’s Leqembi (lecanemab) for the treatment of Alzheimer’s disease, recent data from the Mayo Clinic Study of Aging sheds light on the limited eligibility criteria for the anti-amyloid treatment.
The Mayo Clinic collected data from 237 individuals between the ages of 50 and 90 years of age with mild dementia and evidence of amyloid-ß plaque deposits in the brain. The research, published recently in the journal Neurology, indicates that only a small percentage of individuals with early Alzheimer’s meet the criteria for clinical trial inclusion.
At the same time, researchers found that after the exclusions—including stroke, cardiovascular disease, a history of cancer, and brain scan findings that showed abnormalities like old, small brain bleeds or brain injuries due to insufficient blood supply—only 19 people, or 8%, would have been eligible for a trial.
“Only a small percentage of people with early Alzheimer’s disease may be eligible to receive treatment, mostly due to chronic health conditions and brain scan abnormalities common in older adults,” study author Maria Vassilaki, an epidemiologist at Mayo Clinic, said in a statement.
Vassilaki contends that the challenge is that the inclusion and exclusion criteria of the clinical trials that led to FDA accelerated approval “form the basis of how people should be invited or discouraged” from receiving the drug.
Leqembi is a monoclonal antibody that binds to soluble amyloid beta protein species and plaques and is administered intravenously every two weeks. A Phase III clinical trial demonstrated that the drug slowed down the disease’s progression and increased patients’ quality of life.
Its label states that Leqembi should be used in “patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials” as “there are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied.”
Eisai’s Deputy Chief Clinical Officer Michael Irizarry acknowledged that because Leqembi is only approved for individuals in the early stages of the disease, its target population is small. “Many patients, by the time they’re diagnosed or by the time that they’re considered for potential treatment, are already in the moderate or severe stages of Alzheimer’s disease,” Irizarry told BioSpace.” Those patients are ineligible for Leqembi.
In addition, if tests show that an individual’s memory problems are not due to elevated amyloid in the brain, they would be disqualified from treatment initiation.
“Amyloid plaque deposits in the brain are required for the diagnosis of Alzheimer’s disease. Lecanemab binds to those and clears [them] from the brain,” Irizarry said.
While over 47% of the Mayo Clinic’s study participants fit the criteria to participate in clinical trials for the drug based on memory test and BMI scores, trial exclusion criteria like prior health conditions narrowed that number to just 8%. However, Irizarry says some of these patients could still be eligible for Leqembi.
“The results have to be interpreted in the context of what they looked at,” Irizarry said, noting that the research narrowly analyzed eligibility based on clinical trial criteria. “That can really vary in terms of the types of patients that are being screened and entered in a clinical trial,” he said.
An individual may not qualify for clinical trials, but based on label indication could still later qualify for treatment if their condition stabilized. “It makes good medical sense to control people’s ongoing medical conditions before initiating Leqembi,” Irizarry added.
However, according to Vassilaki, older Black and Hispanic people have been underrepresented in clinical trials, even though they are more likely to have Alzheimer’s or other dementias. Of the 859 people infused with lecanemab during the trial, only 20 were Black.
Vassilaki contends that evaluating the eligibility criteria in more diverse populations is critical.
“Additional research is needed to examine the safety and efficacy of monoclonal antibodies targeting amyloid-ß plaques in larger, more diverse populations, as well as in less healthy populations, before these therapies may be more widely available to people with Alzheimer’s disease,” she said.
Katie Brown is a freelance writer based in Philadelphia. She can be reached at katiebrown926@gmail.com.
