The FDA on Thursday gave full approval to what many scientists and doctors believe is the first drug to show promise of slowing the progression of Alzheimer鈥檚 disease.
But while patient advocates are celebrating, critics see it as the unfortunate triumph of a flawed theory of the disease鈥檚 cause and predict the rollout of the drug will aggravate racial disparities in elder care.
An FDA advisory panel last month voted 6-0 to support FDA approval of lecanemab, from the Japanese pharmaceutical company Eisai. In a clinical trial involving nearly 1,800 early-stage Alzheimer鈥檚 patients, the drug slowed progression of the disease somewhat in those who got biweekly infusions, compared with those given a placebo.
But the drug didn鈥檛 reverse Alzheimer鈥檚 symptoms, and it will require careful monitoring of patients for months or years, including many brain scans. Those receiving lecanemab, which carries the brand name Leqembi, were twice as likely as placebo recipients in the major trial to suffer hemorrhaging or swelling in the brain. These incidents, related to the drug鈥檚 stripping away of amyloid proteins, were generally minor, but three deaths appear to have been caused by the drug.
With the FDA’s approval of lecanemab, Eisai is set to to the primary care physicians who treat most dementia patients and 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鈥檛 benefit lower-income patients, who tend to be diagnosed too late for the drug to be effective, and usually receive care in settings ill-equipped to handle the drug鈥檚 stringent requirements.
鈥淭he most likely consequence of this medication is to take resources and attention away from addressing basic supports for older adults with cognitive impairment,鈥 said Maria Glymour, chair of the Department of Epidemiology at the Boston University School of Public Health. The money spent on expensive drugs like lecanemab would be better invested in fighting diseases like high blood pressure and diabetes, which hasten dementia, and on community-based services for older adults, she said.
The critique of lecanemab builds on another complexity of the drug鈥檚 approval: Few African Americans were involved in testing it.
Of the 859 people infused with lecanemab during the trial, . Minorities are often underrepresented in research, but this study had an additional barrier, said Carey Gleason, a clinical neuropsychologist at the University of Wisconsin School of Medicine and Public Health. Many Black volunteers in the trial 鈥渟creened out,鈥 she said, because PET scans showed relatively low levels of amyloid in their brains. Lecanemab works by removing amyloid, so the trial organizers excluded patients 鈥 regardless of their Alzheimer鈥檚 symptoms 鈥 if their PET scans were negative.
Eisai spokesperson Libby Holman said the company worked to enroll a diverse population but that amyloid levels 鈥渄iffered among racial and ethnic groups.鈥 She added, 鈥淚f individuals do not have elevated amyloid, they do not have Alzheimer鈥檚 disease.鈥
Indeed, lecanemab鈥檚 approval marks the culmination of the idea, , that Alzheimer鈥檚 disease can be understood as cognitive decline , the 鈥渢rigger,鈥 in combination with the 鈥渂ullet,鈥 a protein called tau.
For example, Blacks are up to twice as likely as whites to have Alzheimer鈥檚, yet they show equivalent levels of amyloid in most major studies. No one is sure why, but the hypothesis is that having multiple simultaneous health conditions and being exposed to environmental stressors put Blacks as a group at higher risk.
Furthermore, Blacks and other minorities tend to be diagnosed at later stages, which automatically excludes them from use of lecanemab, which was designed and approved to treat early-stage Alzheimer鈥檚.
鈥淭he drug has to be used in the very early window of the disease,鈥 Gleason said. 鈥淚t鈥檚 well documented that marginalized communities and people don鈥檛 get access to diagnostic services as do more privileged populations, because our medical care is two-tiered.鈥
鈥淟ecanemab should still come to market,鈥 she said. 鈥淏ut we need to be investing in other pathways.鈥
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. Its rollout would aggravate elder care disparities, the panel said, by favoring wealthier patients who have more resources, better insurance, and an easier time getting to multiple appointments.
Advocates for minority health care are well aware of these risks. But many feel the only response is to push harder for access to the drug. There is no research to suggest the drug would not work in Black people, said Carl Hill, chief diversity, equity and inclusion officer for the Alzheimer’s Association, which is raising awareness of the drug through churches and grassroots groups.
Manly is not so sure. 鈥淭here are reasons to question whether it would be safe in Black people,鈥 she said, noting that older Black people diagnosed with dementia have higher rates of vascular conditions like hardening of the arteries compared with white patients. That could pose potentially higher risks of brain hemorrhaging if they took the drug. In general, the trial鈥檚 lack of representativeness across racial and ethnic groups means the drug may not perform as well against Alzheimer鈥檚 disease across these groups, Manly said.
鈥淚n terms of equity I feel conflicted,鈥 she said. 鈥淚鈥檇 love for all families like mine to have equitable access to an Alzheimer鈥檚 drug, but only if it鈥檚 safe and effective.鈥
Even the most optimistic Alzheimer鈥檚 experts believe the drug鈥檚 risks of patients by highly trained clinicians with sufficient resources to detect and monitor any problems.
Jason Karlawish, a neurologist at the Perelman School of Medicine at the University of Pennsylvania, said the FDA should set up a Risk Evaluation and Mitigation Strategy, or REMS, which would require doctors administering the drug to follow a series of steps to reduce and monitor its dangers. A REMS, currently in place on , generally limits access to a drug. While FDA’s approval of lecanemab warned of risks, especially for people who are on blood thinners, it did not require a REMS.
The conflict between safety and access is only one paradox of lecanemab鈥檚 arrival.
The FDA anti-amyloid treatment, Aduhelm, in 2021. but most doctors rejected it as ineffective and unsafe. Some Alzheimer鈥檚 scientists who that amyloid isn鈥檛 the whole answer feel that lecanemab鈥檚 middling performance only confirms their thesis.
One skeptic is George Perry, a neurobiology professor at the University of Texas at San Antonio. He has hypothesized that amyloid and tau buildup are a reaction to the aging process that play a role in preserving, rather than wrecking, the brain. The accumulation of amyloid in older people鈥檚 brains, in Perry鈥檚 view, reflects the body鈥檚 effort to fight aging disease.
Dementia clearly has many causes, said S. Ahmad Sajjadi, a clinician and neuroscientist at the University of California-Irvine. Ideally, patients will someday 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 鈥 perhaps a 10% chance of freezing the progression of the disease for months or even longer.
Patient groups such as the Alzheimer鈥檚 Association, which funds much of the research in the field, are demanding broad access to lecanemab and oppose the Biden administration鈥檚 plan to have Medicare initially pay for the drug only if patients are enrolled in a registry, a kind of post-marketing clinical trial.
At a public hearing during the FDA advisory panel meeting on the drug, Alzheimer鈥檚 Association CEO Joanne Pike noted that patients on lecanemab declined five months more slowly in their first 18 months on the drug, on average. That 鈥渄eserves celebration,鈥 she said.
Perry, who has received research funding from the Alzheimer鈥檚 Association, questions its strong support for the drug but isn鈥檛 surprised, given the group鈥檚 promise to its members and supporters to help find a cure for the disease.
鈥淭hey鈥檝e pushed amyloid so hard for 30 years,鈥 he said, 鈥渁nd they can鈥檛 turn back.鈥
