Alzheimer’s: Medicines benefit whites more than blacks – 07/31/2023 – Health

Innovative Alzheimer’s treatments that work by removing a toxic protein called beta-amyloid from the brain may benefit white Americans more than black Americans, Alzheimer’s experts told Reuters.

The two drugs—Leqembi, from biotech partners Eisai (4523.T) and Biogen (BIIB.O), and an experimental treatment developed by Eli Lilly (LLY.N), donanemab—are the first to offer real hope of slowing down the fatal disease for the 6.5 million Americans living with Alzheimer’s.

Although older black Americans have twice the rate of dementia than whites, they screened out of clinical trials of these drugs at a higher rate, according to interviews with 10 researchers, as well as four executives from Eisai and Lilly.

Potential black volunteers with early symptoms of the disease did not have enough amyloid in their brains to qualify for testing, the researchers explained.

Hispanics, who have dementia at one and a half times the rate of whites, were also excluded at a slightly higher rate because of low amyloid, although the issue was not as pronounced as it was for black people, five of the researchers said.

Mounting evidence of a disparity around amyloid, a defining feature of Alzheimer’s, is raising questions among some scientists about who will benefit from the two new treatments — the first ever proven to slow the rate of cognitive decline, according to the researchers.

Referring to Leqembi, Dr. Crystal Glover, a social psychologist and aging equity research expert who leads clinical trial recruitment for the Rush Alzheimer’s Disease Research Centerin Chicago asked, “Is this really applicable to groups that are most at risk?”

It is estimated that about 20% of older black people have Alzheimer’s or another dementia, double the rate of white people and over 14% of Hispanics.

Some researchers are asking whether black patients have dementia due to causes other than Alzheimer’s or whether the disease manifests itself differently in different populations with higher rates of chronic conditions.

The beta-amyloid disparity is mounting evidence that some health metrics may not work as well in diverse populations as they do in white people.

Leqembi is being launched at a price of $26,500 per year after receiving full US regulatory approval this month.

A spokesman for the US Food and Drug Administration (FDA) said the agency was aware of the potential exclusion of some African Americans from new treatments due to insufficient levels of amyloid.

The spokesperson said the FDA encourages companies to increase enrollment of diverse populations in their ongoing trials. In April 2022, the FDA recommended that companies submit a diversity plan for enrollment.

“Not designed for specific ethnic groups”

Eisai said it is working to understand why so many people of color seeking to enroll in its clinical trial for Leqembi have been screened for a lack of amyloid. The company told Reuters that 49% of black volunteers did not meet the test’s amyloid threshold requirements, compared with 22% for whites and 55% for Hispanics.

That left just 43 black participants out of 947 people enrolled in the US portion of the study, or 4.5% of the total — a glaring underrepresentation given that the disease is more prevalent for black Americans and they make up 13.7% of the population. from the USA.

Despite flaws in amyloid screening, Hispanics made up 22.5% of the US arm of the Eisai trial, an overrepresentation compared to the US population.

“Is it because MCI (mild cognitive impairment) or early dementia symptoms in black people are caused by reasons other than Alzheimer’s?” Eisai US chief Ivan Cheung said in an interview with Reuters. “We are investigating.”

Only people who are amyloid-positive should receive Leqembi “regardless of race and ethnicity,” Cheung said: “The drug is not designed to help specific ethnic groups or races.”

Tokyo-based Eisai is working with the National Institutes of Health (NIH), a US government health research agency, to test Leqembi’s effectiveness in preventing Alzheimer’s among people with elevated amyloid cognition but normal.

The company is targeting at least 8% black enrollment in the 1,400-person trial, Shobha Dhadda, global head of biostatistics at Eisai, told Reuters. So far, 95% to 98% of black applicants are failing to meet the amyloid threshold required for inclusion, she said.

Biogen, Eisai’s partner, did not participate in the development of Leqembi, but has rights to sell the drug.

Black and Hispanic people were also screened at slightly higher rates in Lilly’s trial of investigational drug donanemab, said Dr. Mark Mintun, Lilly’s group vice president for neuroscience research and development. The drug is under review by the FDA.

In the US, 4% of participants were black and 6% were Hispanic, Lilly said. The company said it recognizes that these numbers are low despite its efforts to increase recruitment and that it intends that enrollments in its US tests generally reflect the makeup of the population.

Lilly said that research into why black and Hispanic people were screened out of tests at higher rates is ongoing and that there are many hypotheses, including that the dementia is not caused by Alzheimer’s, or that they are in an earlier stage of Alzheimer’s, but that his illness is complicated by other factors, such as small strokes.

Clinical trials typically have low enrollment from diverse populations: among US trials reporting race and ethnicity, about 80% of participants were white; 10%, black; 6% Hispanic and 1% Asian, according to a 2022 study. In 96 dementia trials from 2000 to 2017, diverse populations accounted for only about 11% of enrollments, according to a 2018 study.

biological markers

Alzheimer’s researchers have moved away from using external cues — such as memory loss — to identify patients with the disease and detect Alzheimer’s-associated proteins in the body, including amyloid.

However, some tests that are used to identify these proteins may perform differently between black and white patients.

Differences in Alzheimer’s drivers were seen in a small 2015 study comparing the brains of black and white individuals who died from the disease.

The study, led by Dr. Lisa Barnes, who is also at the Rush Center, found that white people were more likely to carry proteins associated with Alzheimer’s as the main driver of dementia. Among blacks who died of Alzheimer’s, the dementia likely had multiple causes, such as vascular disease.

Later studies involving brain scans, spinal fluid and blood tests—many citing Barnes’s work—also found differences.

In a 2021 article published in Nature Reviews NeurologyBarnes argued that scientists need a better understanding of Alzheimer’s in people of color or else effective treatments would not be available for this at-risk but underrepresented population.

“We are seeing that come to the fore with this recent drug,” Barnes said in an email to Reuters, referring to Leqembi.

“We need to know what pathologies other than amyloid lead to dementia in blacks and how risk factors, especially socially constructed risk factors, relate to these pathologies,” said Barnes.

The Doctor. Joshua Grill, an Alzheimer’s researcher at the University of California, Irvine, who collaborated with Eisai and other researchers to analyze two trials for Leqembi and two for an earlier anti-amyloid drug, also found that blacks, Hispanics and Asians were more likely to be screened. out of clinical trials because the amount of amyloid in the brain was below the trial threshold. The researchers intend to submit the results for publication.

“Could it be Alzheimer’s disease? Is something else causing their cognitive problems in all these studies? Could it be that the biomarkers don’t work the same in these communities, or is it something else that we can’t measure?” Grill said.

Two researchers told Reuters that a possible explanation for the differences in amyloid is APOE4, the variant of a gene that regulates amyloid deposits in the brain and which is associated with an increased risk of late-onset Alzheimer’s. The risk of developing the disease among people with the variant is highest in those of Asian or European descent and lowest in people of African and Hispanic descent, according to the National Institutes of Health (NIH).

Differences in APOE4 may help explain why more black people are failing to reach the amyloid thresholds needed for recent drug testing, said Dr. Reisa Sperling of Brigham and Women’s Hospital, who is leading Leqembi’s trial to prevent Alzheimer’s dementia. Other factors may be at play, according to experts.

In the United States, more than 75% of black Americans are overweight or obese, increasing their risk of hypertension, high cholesterol, type 2 diabetes and sleep apnea — factors that increase the risk of vascular dementia, according to government data. American. Socioeconomic factors play a role in obesity and may also play a role in dementia.

Several recent studies are finding that racism and the resulting inequalities in income, access to high-quality medical care and healthy food, exposure to pollution, and chronic stress affect the health, and possibly the underlying biology, of different populations.