Why Alzheimer’s Next Big Hope Might Not Help Most Black Patients

This week, the FDA is expected to approve what many scientists and doctors believe is the first promising drug to slow the progression of Alzheimer’s disease.

But while patient advocates celebrate, critics see it as the unfortunate triumph of a flawed theory of the cause of the disease and predict that rolling out the drug will deepen racial disparities in care for the elderly.

Last month, an FDA advisory committee voted 6-0 to support FDA approval of lecanemab, from Japanese pharmaceutical company Eisai. In a clinical trial involving nearly 1,800 patients with early-stage Alzheimer’s disease, the drug slowed disease progression somewhat in those who received infusions every two weeks, compared to those who received a placebo.

But the drug did not reverse Alzheimer’s symptoms, and it will require careful monitoring of patients for months or years, including numerous brain scans. Those who received lecanemab, which goes by the brand name Leqembi, were twice as likely as placebo recipients in the major trial to experience bleeding or swelling in the brain. These incidents, related to the removal of amyloid proteins by the drug, were generally minor, but three deaths appear to have been caused by the drug.

As the FDA nears full approval of lecanemab and Eisai prepares to promote it to primary care physicians who treat most dementia patients, critics are speaking out. Some say the drug, which Eisai plans to market for $26,500 a year, offers false hope. Others say any positive impact it has won’t benefit low-income patients, who tend to be diagnosed too late for the drug to be effective, and typically receive care in settings ill-equipped to handle the demands. drug strictures.

“The most likely consequence of this drug is to divert resources and attention away from caring for basic supports for older adults with cognitive impairment,” said Maria Glymour, chair of the department of epidemiology at the Boston University School of Public Health. Money spent on expensive drugs like lecanemab would be better spent fighting diseases like high blood pressure and diabetes, which hasten dementia, and community services for the elderly, she said. .

Lecanemab’s criticism hinges on another complexity of drug approval: Few African Americans participated in its testing.

Of the 859 people infused with lecanemab during the trial, only 20 were black. Minorities are often underrepresented in research, but this study had an additional hurdle, said Carey Gleason, a clinical neuropsychologist at the University of Wisconsin School of Medicine and Public Health. Many black volunteers in the trial “were eliminated,” she said, because PET scans showed relatively low levels of amyloid in their brains. Lecanemab works by removing amyloid, so trial organizers excluded patients – regardless of their Alzheimer’s symptoms – if their PET scans were negative.

Eisai spokeswoman Libby Holman said the company strives to enroll a diverse population, but amyloid levels “differ across racial and ethnic groups.” She added: “If individuals don’t have elevated amyloid, they don’t have Alzheimer’s disease.”

Indeed, the approval of lecanemab marks the culmination of the idea, formalized 32 years ago, that Alzheimer’s disease can be understood as a cognitive decline caused by the accumulation of amyloid, the “trigger”. , in combination with the “bullet”, a protein called tau.

For example, blacks are up to twice as likely as whites to be diagnosed with Alzheimer’s disease, while showing equivalent levels of amyloid in most major studies. No one is quite sure why, but the hypothesis is that having multiple concurrent health conditions and being exposed to environmental stressors puts black people as a group at higher risk.

Additionally, blacks and other minorities tend to be diagnosed at later stages, automatically excluding them from the use of lecanemab, which was designed and approved to treat early-stage Alzheimer’s disease.

“The drug should be used in the very first window of illness,” Gleason said. “It is well documented that marginalized communities and individuals do not have access to diagnostic services as more privileged populations do, because our medical care is two-tiered.”

“Lecanemab is still expected to hit the market,” she said. “But we have to invest in other ways.”

In its review of the costs and benefits of lecanemab, a 15-member panel appointed by the Institute for Clinical and Economic Review gave the drug low marks. Rolling it out would worsen disparities in care for the elderly, the panel said, by favoring wealthier patients who have more resources, better insurance and easier time getting to multiple appointments.

Minority health care advocates are well aware of these risks. But many believe the only answer is to push harder for access to the drug. Black people whose conditions qualify them for the drug would fare just as well as white people, said Carl Hill, head of diversity, equity and inclusion for the Alzheimer’s Association, which raises awareness of the drug through through local churches and groups.

Manly isn’t so sure. “There’s reason to wonder if it would be safe in black people,” she said, noting that older black people diagnosed with dementia have higher rates of vascular disease like hardening of the arteries by compared to white patients. This could pose potentially higher risks of brain hemorrhage if they took the drug. In general, the trial’s lack of representativeness across racial and ethnic groups means the drug may not be as effective against Alzheimer’s disease in those groups, Manly said.

“In terms of fairness, I feel conflicted,” she said. “I wish all families like mine had equal access to an Alzheimer’s drug, but only if it’s safe and effective.”

Even the most optimistic Alzheimer’s disease experts believe the drug’s risks require careful patient selection by highly trained clinicians who are well-resourced to detect and monitor any problems.

Jason Karlawish, a neurologist at the University of Pennsylvania’s Perelman School of Medicine, said the FDA should put in place a risk assessment and mitigation strategy, or REMS, that would require physicians administering the drug to follow a series of steps to reduce and monitor its perils. A REMS, currently in place for around 60 drugs, generally limits access to a drug.

The conflict between security and access is only one of the paradoxes of the arrival of lecanemab.

The FDA approved an earlier anti-amyloid treatment, Aduhelm, in 2021, but most doctors dismissed it as ineffective and dangerous. Some Alzheimer’s scientists who have long argued that amyloid is not the complete answer believe that lecanemab’s poor performance only confirms their thesis.

One skeptic is George Perry, professor of neurobiology at the University of Texas at San Antonio. He hypothesized that the buildup of amyloid and tau is a reaction to the aging process that plays a role in preserving, rather than destroying, the brain. The buildup of amyloid in the brains of older people, according to Perry, reflects the body’s effort to fight the disease of aging.

Dementia clearly has many causes, said S. Ahmad Sajjadi, a clinician and neuroscientist at the University of California, Irvine. Ideally, patients will one day receive treatments as specific and targeted as those increasingly available to treat cancers, he said.

For now, for a select group of patients, lecanemab offers a whisper of hope that some will want to pursue, despite the risks, Karlawish said — perhaps a 10% chance of freezing disease progression for months. , see more.

Patient groups such as the Alzheimer’s Association, which funds much of the research in the field, are calling for broad access to lecanemab and opposing the Biden administration’s plan to initially have Medicare pay for the drug only if patients are enrolled in a registry, a sort of post-marketing clinical trial.

In a public hearing at the FDA drug advisory committee meeting, Alzheimer’s Association CEO Joanne Pike noted that patients on lecanemab declined five months slower during their first 18 months of treatment, on average. It “is worth celebrating,” she said.

Perry, who has received research funding from the Alzheimer’s Association, questions its strong support for the drug but isn’t surprised, given the group’s promise to its members and supporters to help find a cure for the disease. disease.

“They’ve been pushing amyloid so hard for 30 years,” he said, “and they can’t go back.”