Leqembi won conditional FDA approval earlier this year based on how well it helped remove plaques from the brain that are thought to play a role in cognitive decline.
The U.S. Food and Drug Administration (FDA) has granted full approval for Leqembi (lecanemab), a medicine designed to slow the progression of early-stage Alzheimer’s disease.
Lecanemab won conditional FDA approval in January, based on study results showing that it could help clear the brain of a substance known as amyloid plaque that is thought to contribute to cognitive decline associated with Alzheimer’s disease. Now, the FDA has awarded full approval based on new study findings confirming that lecanemab can stall cognitive problems in people with early Alzheimer’s disease.
This is the first time the FDA has verified that “a drug targeting the underlying disease process of Alzheimer’s disease has shown clinical benefit,” according to a statement from Teresa Buracchio, MD, acting director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research. “This confirmatory study verified that it is a safe and effective treatment for patients with Alzheimer’s disease.”
Leqembi Could Help Millions of Americans With Early Alzheimer’s Full approval of lecanemab may help up to about five million people nationwide who currently have mild cognitive impairment due to Alzheimer’s disease, says James Galvin, MD, MPH, a professor and director of the Comprehensive Center for Brain Health at the University of Miami Miller School of Medicine in Florida.
When the drug only had conditional approval, Medicare, the U.S. health program for people 65 and older, said it would limit coverage for lecanemab to people receiving it through clinical trials, greatly restricting access. Medicare also said it would expand coverage for lecanemab once the medicine received full FDA approval.
“The decision for full approval for lecanemab is an important milestone for every patient living with Alzheimer’s disease, every family with a loved one who is affected by Alzheimer’s disease, and indeed every person at-risk for developing Alzheimer’s disease in the future,” says Dr. Galvin. “It has been nearly two decades since the last Alzheimer's treatment received full FDA approval, and never before has a disease-modifying medication received full FDA approval.”
New Drug Fulfills Unmet Need in Dementia Treatment Alzheimer’s disease is the most common form of dementia among older adults, according to the Centers for Disease Control and Prevention (CDC). An estimated 6.5 million Americans are currently living with the condition, and it’s the fifth leading cause of death among people 65 and older.
Other drugs with full FDA approval for Alzheimer’s disease target symptoms but don’t address the underlying causes. The newest of these medicines to manage dementia symptoms is Namenda (memantine), which received full FDA approval two decades ago. Older options that help with Alzheimer’s symptoms include Aricept (donepezil), Razadyne (galantamine), and the combination drug Namzaric (memantine and donepezil). Lecanemab is the first medicine known as an amyloid antibody — designed to help clear the brain of plaque deposits that may hasten cognitive decline due to Alzheimer’s disease — to win full FDA approval. One other amyloid antibody, Aduhelm (aducanumab), won conditional FDA approval in 2021 despite an FDA advisory committee recommendation against it, due to concerns about the lack of clear benefits. Aduhelm had mixed results in clinical trials, with benefits seen in some studies but not others, and has yet to receive full FDA approval.
Lecanemab Slows Cognitive Decline, But Comes With Some Risks\ In a late-stage clinical trial of lecanemab published in January in The New England Journal of Medicine (NEJM), people taking the drug experienced 27 percent slower cognitive decline than participants who received a placebo.
Statistically, this is a fairly modest effect, Galvin says. However, “many patients and families would gladly have Alzheimer's disease slowed and live their lives with a longer time at the mild stage of disease,” Galvin adds. One safety concern with lecanemab is the potential for people who take this drug and other amyloid antibodies to experience what’s known as ARIA, or amyloid-related imaging abnormalities. ARIA shows up on brain scans and can sometimes involve brain swelling or bleeding, although many people don’t experience symptoms.
In the late-stage lecanemab trial, 17 percent of people on lecanemab experienced ARIA with brain bleeding, and 12 percent had ARIA with swelling in the brain, according to results in NEJM.
ARIA most commonly appears as temporary brain swelling in areas of the brain seen on imaging studies. It usually resolves over time and may be accompanied by small spots of bleeding in or on the surface of the brain, the FDA said in its statement announcing full approval for lecanemab. More rarely, ARIA can be associated with life-threatening bleeding or swelling in the brain, seizures, and other severe neurological symptoms.
In granting full approval, the FDA required Leqembi to carry a so-called black box warning in its packaging information alerting patients to the potential risks associated with ARIA. Benefits Appear to Outweigh Risks for Many People With Early Alzheimer’s For people living with early-stage Alzheimer’s disease, this risk so far appears to be worth it when considered against the benefits of lecanemab, says Sharon Cohen, MD, a behavioral neurologist and medical director of the Toronto Memory Program in Canada.
“The benefits of disease slowing, and the relative preservation of daily function and quality of life for patients and families, outweigh the small risks of serious side effects,” Dr. Cohen says.
It’s still not clear, however, exactly how long lecanemab might help people with early-stage Alzheimer’s avoid more serious decline, says Mia Yang, MD, an assistant professor of gerontology and geriatrics at Wake Forest School of Medicine in Winston-Salem, North Carolina.
“It's possible that earlier improvement in the disease progression could translate to larger improvement down the line, but we do not have enough data to conclude that definitively,” Dr. Yang says.
“I think those with early onset Alzheimer's disease, who have memory loss that is not normal aging in their late fifties [to] early sixties, without many medical comorbidities, are the most likely candidates to benefit, and with whom I'm already having discussions about lecanemab.”