New Alzheimer’s drugs may benefit whites more than black Americans, leading Alzheimer’s experts told Reuters. Leqembi and donanemab are the first Alzheimer’s drugs to offer real hope of slowing cognitive decline for the 6.5 million Americans living with Alzheimer’s.
Black Americans have twice the rate of dementia as whites. They were screened out of clinical trials of these drugs. The black volunteers with early disease symptoms did not have enough amyloid in their brains to qualify for the trials, the 10 researchers explained.
Hispanics, who experience dementia at one and a half times the rate of whites, were also excluded at a somewhat higher rate due to low amyloid.
Who will Benefit from the Two New Alzheimer’s Drugs?
The growing evidence of a disparity around amyloid 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, the researchers said.
Dr. Crystal Glover, a social psychologist and expert in equity in aging research who leads clinical trial recruitment of the Rush Alzheimer’s Disease Research Center in Chicago, asked referring to Leqembi, “Is this even applicable to the groups that are most at risk?”
About 20% of older black adults are estimated to have Alzheimer’s or another dementia, twice the rate of white people and above the 14% of Hispanics. Some researchers are asking whether black patients are experiencing dementia due to causes other than Alzheimer’s or whether the disease manifests differently in diverse populations who have higher rates of chronic conditions.
The disparity in beta-amyloid is adding to evidence that some health metrics may not work the same in diverse populations as they do in white people. Leqembi was launched with a price of $26,500 per year after it received full US regulatory approval last month.
An FDA spokesperson said the agency was aware of the potential exclusion of some African Americans from the new treatments due to insufficient amyloid levels. The FDA encourages companies to increase enrollment of diverse populations in their clinical trials. Last year they recommended companies submit a diversity plan for enrollment.
Blacks Underrepresented in New Alzheimer’s Drugs Clinical Trials
Eisai said it is working to understand why so many black people were screened out due to a lack of amyloid. The company told Reuters that 49% of black volunteers did not meet the trial’s amyloid threshold requirements compared to 22% for whites and 55% for Hispanics. There were 43 black participants out of 947 people enrolled or 4.5% of the total. This is an underrepresentation since the disease is most prevalent for black Americans and they make up 13.7% of the U.S. population.
Only people who are amyloid positive should get Leqembi, regardless of race and ethnicity. The drug was not designed to help specific ethnic groups or races.
Shobha Dhadda, Eisai’s global head of biostatistics, told Reuters that they are targeting black enrollment of at least 8% in the 1,400-person trial, But, 95% to 98% of black candidates are failing to meet the amyloid threshold required for inclusion.
Blacks and Hispanics were also screened out at somewhat higher rates in the trial for donanemab. Only 4% of the participants were black and 6% were Hispanic. Lilly said it recognized those numbers were low despite its efforts to increase recruitment and that it aims to have enrollment in its US trials overall reflect the make-up of the population.
Clinical trials typically have low enrollment of diverse populations. In trials that reported race and ethnicity, about 80% of participants were white, 10% were black, 6% were Hispanic and 1 percent were Asian, a 2022 study found.
In a small 2015 study, differences in the drivers of Alzheimer’s were noted by comparing the brains of black and white individuals who died of the disease.
The study, led by Dr. Lisa Barnes, at the Rush Alzheimer’s Disease Research Center, found that white people were more likely to carry Alzheimer’s associated proteins as the primary driver of their dementia. For black people who died of Alzheimer’s, their dementia was more likely the result of multiple causes, including vascular disease. Subsequent studies involving brain scans, spinal fluid, and blood tests – many citing Barnes’ work – have also found differences.
In a 2021 paper published in Nature Reviews Neurology, Barnes argued that scientists need a better understanding of Alzheimer’s in black people or else effective treatments would not be available to this at-risk, and underrepresented population.
“We need to know what the other pathologies are beyond amyloid that leads to dementia in black people, and how risk factors, especially socially constructed risk factors, relate to those pathologies,” Barnes said.
Two researchers told Reuters one possible explanation for the differences in amyloid is APOE4, a variant of a gene that regulates amyloid deposits in the brain and that is associated with a greater risk of late-onset Alzheimer’s. The risk of developing the disease among people with the variant is higher in those of Asian or European ancestry and lower in people of African and Hispanic ancestry, according to the National Institutes of Health (NIH).
Differences in APOE4 could help explain why more black people are failing to meet the amyloid thresholds required for recent drug trials, said Dr. Reisa Sperling of Brigham and Women’s Hospital, who is leading the trial of Leqembi to prevent Alzheimer’s dementia. Other factors could be at play, experts said.
More than 75% of black Americans are overweight or obese, increasing their risk of hypertension, high cholesterol, type 2 diabetes, and sleep apnea. These are all factors that raise the risk of vascular dementia. Socioeconomic factors play a role in obesity and may play a role in dementia.
Several recent studies are finding that racism, and resulting inequities 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.