Only a small proportion of older adults with early symptoms of Alzheimer's disease are eligible to receive a new monoclonal antibody treatment, according to a recent study. The study highlights the need for broader clinical trial standards and increased representation of diverse populations.
A limited proportion of older adults in the early stages of Alzheimer's disease are eligible for the latest monoclonal antibody therapies, which are designed to target amyloid-β deposits in the brain, a preliminary indicator of Alzheimer's disease.
The findings were recently published in Neurology, the medical journal of the American Academy of Neurology. Clinical trial results for these drugs apply only to patients with early symptoms of Alzheimer's disease, mild cognitive impairment, or mild dementia.
At the time of this study, two monoclonal antibodies called lecanimab and aducanumab had received accelerated approval from the U.S. Food and Drug Administration. More recently, lecanimab has been shown to slow disease progression and received conventional approval from the U.S. Food and Drug Administration.
"These new treatments for Alzheimer's hold promise in slowing the progression of the disease in many people, but the reality is that these drugs have only been studied in patients with the earliest stages of Alzheimer's disease," said study author Maria Vassilaki, MD, of the Mayo Clinic in Rochester, Minn., and a member of the American Academy of Neurology. The U.S. Food and Drug Administration's (FDA) inclusion and exclusion criteria for accelerated approval of clinical trials of these therapies form the basis for how people are invited or prevented from receiving these drugs. Our study estimates that only a small proportion of older adults with early cognitive impairment due to Alzheimer's disease may be eligible for treatment with a monoclonal antibody that targets amyloid-β in the brain."
The study included 237 people aged 50 to 90 with mild cognitive impairment, or mild dementia, whose brain scans showed increased numbers of amyloid-β plaques. The researchers then examined eligibility criteria for clinical trials of laikazumab and aducanumab.
For lecanemab, clinical trial inclusion criteria required specific scores on various thinking and memory tests, as well as a body mass index between 17 and 35. The researchers found that 112 people (47%) met the inclusion criteria to participate in the clinical trial. The researchers then looked at clinical trial exclusions, factors that might make a person ineligible for a trial, including a variety of health factors such as a history of stroke, cardiovascular disease, cancer, or abnormalities on brain scans such as old cerebellar hemorrhages or brain damage caused by insufficient blood flow. The researchers found that after excluding these factors, only 19 people, or 8%, were eligible to participate in the lecanizumab trial.
However, after modifying the exclusion criteria to include all patients with mild cognitive impairment and without using additional memory and thinking test results, 17% of patients with mild cognitive impairment would be eligible for the trial.
For aducanumab, clinical trial inclusion criteria required specific scores on thinking and memory tests and that participants be between 50 and 85 years old. The researchers found that 104 people, or 44%, met the characteristics required to participate in the clinical trial. After further examining who was excluded from the trial due to a variety of health factors, including stroke, cardiovascular disease, uncontrolled high blood pressure, a history of cancer or brain scan results, the researchers found that only 12 people, or just 5%, were eligible for the aducanumab trial.
Vasilaki noted that black and Hispanic older adults are underrepresented in clinical trials, even though they are more likely to have Alzheimer's or other dementias. "Our findings suggest that only a small proportion of people with early-stage Alzheimer's disease may be eligible for treatment, primarily due to chronic health conditions and brain scan abnormalities common in older adults. In general, clinical trial participants are healthier than the general population. More studies are needed examining the safety and effectiveness of monoclonal antibodies targeting amyloid-β plaques in larger, more diverse populations, as well as in less healthy people, before these therapies can be made more widely available to people with Alzheimer's disease."