Many Ineligible for New Alzheimer’s Drugs: Study

Vials and packaging for Eisai's medication Leqembi. Eisai via AP

A new class of Alzheimer’s drugs offers hope of slowing cognitive decline. However, emerging research shows that only a fraction of patients may qualify for these potentially life-changing treatments due to underlying health conditions that could compromise their effectiveness.

The Drugs Approved for Alzheimer’s

In January, a large clinical trial found that a biweekly IV infusion of lecanemab (Leqembi) slowed cognitive decline by 25 percent in patients with early Alzheimer’s. By July, lecanemab received full approval from the U.S. Food and Drug Administration (FDA) for treatment in the early stages of the disease, becoming the second of a new category of medications approved for the disease, the first being aducanumab (Aduhelm).

These drugs target beta-amyloid plaques, identified as a sign of Alzheimer’s disease. While these plaques, which form when beta-amyloid protein pieces clump together, may be found in the earliest stages of the neurogenerative disease or mild cognitive impairment (MCI) associated with early Alzheimer’s, they aren’t present in MCI from other causes like vascular issues. This makes them a focus to treat this form of dementia specifically.

However, only a small percentage of patients would be eligible for treatment with these monoclonal antibody drugs if they were selected based on the criteria used in the lecanemab clinical trial, according to research by the Mayo Clinic published in Neurology.

“There is hope that these new therapies for Alzheimer’s may slow progression of the disease for many people, although the fact remains that the drugs have only been studied in people with the earliest forms of the disease,” Dr. Maria Vassilaki, an epidemiologist at the Mayo Clinic and a coauthor of the study, said in a press statement.

Who Is Excluded and Why?

The Mayo Clinic study included 237 participants aged 50 to 90 diagnosed with MCI or early dementia and confirmed beta-amyloid plaques. This is the approved patient population for lecanemab.

Researchers analyzed the drug trial’s eligibility criteria. These included specific body mass index (between 17 and 35), cognition, and memory test scores. Only about 47 percent of participants met these requirements.

Additional exclusions further reduced eligibility. These were cardiovascular disease, stroke, cancer history, prior small brain bleeds, and insufficient brain blood flow injuries. Factoring these in, just 8 percent of the 237 participants would have qualified for the lecanemab trial.

Relaxing cognitive testing—including all patients with MCI without taking additional cognitive tests—increased eligibility to 17.4 percent.

Researchers found similar results for aducanumab. This drug received accelerated approval from the FDA in 2021 but has not yet received full approval.

Aducanumab had similar results. Its trial required specific cognition scores and ages 50 to 85. Only 44 percent of Mayo participants would have met these criteria.

Similar to the exclusion criteria for lecanemab, barring people with histories of stroke, heart disease, uncontrolled blood pressure, and abnormal brain scans further reduced aducanumab eligibility to just 5 percent.

Why Health Conditions Bar Alzheimer’s Drug Access

“There are multiple reasons why someone might be excluded from a clinical trial,” Maria Carrillo, who holds a doctorate in neuroscience and is the chief science officer of the Alzheimer’s Association, told The Epoch Times. “For example, a comorbid condition that impacts cognition may obscure the effect of a treatment and impact the outcome of the trial.”

Another reason certain preexisting health conditions are considered disqualifying is the possibility that the treatment used in a trial could interact directly with that condition, she added.

“The current class of anti-amyloid, monoclonal antibodies seem to have more severe side effects when an individual has more comorbid conditions, especially ones that are vascular,” Ms. Carrillo said.

The lecanemab trials were more inclusive of comorbid patients, she noted. This suggests the drug may be generalizable to broader populations.

“As we enter the treatment era [of Alzheimer’s], this research helps underscore the importance of risk/benefit conversations and determining the most appropriate patients to receive treatment,” she added.

Using the trial criteria to determine drug access will severely restrict eligibility, Dr. Vassilaki said.

“The inclusion and exclusion criteria of the clinical trials that led to FDA accelerated approval of these therapies form the basis of how people should be invited or discouraged from receiving one of these drugs,” Dr. Vassilaki said in the press statement.

She noted more research on safety and efficacy in larger, more diverse populations is needed before monoclonal antibodies can become widely available Alzheimer’s treatments.