FDA Approves New Alzheimer’s Drug

Is lecanemab really a game changer? Learn where treatment stands for this progressive disease.

older woman with dementia being comforted by caregiver

Updated on July 6, 2023.

The Alzheimer’s disease drug lecanemab was granted full approval by the U.S. Food and Drug Administration (FDA) on July 6—nearly seven months after it received accelerated approval in January 2023. The drug, which is made by the Cambridge, Massachusetts-based biotech Biogen and the Japanese pharmaceutical firm Eisai, will be sold under the name Leqembi. It’s one of the first experimental drugs to demonstrate the potential to slow the progression of cognitive decline.

For more than six million Americans currently living with Alzheimer’s disease, finding new treatments that could halt the progression of the disease—or at least slow it down—would be momentous. For years, research in the field has been littered with disappointments. Existing treatments can help manage Alzheimer’s symptoms, but only recently have they begun to target the disease itself. Researchers are investigating experimental drugs that could interrupt the disease process and the destruction of brain cells. Lecanemab is one of these drugs and it’s being touted as a possible game changer.

Clinical trial results presented on November 29, 2022 at a national research conference in San Francisco suggest that lecanemab shows the potential to change the course of Alzheimer’s when started early in the course of the disease, according to Kevin N. Hascup, PhD, assistant professor, Center for Alzheimer’s Research and Treatment at Southern Illinois University School of Medicine. 

“This study gives hope to the scientific community as well as patients living with dementia and their caregivers that we can fight this disease,” Hascup says.

What is lecanemab and how does it work?

Lecanemab belongs to a class of drugs called monoclonal antibodies—laboratory-made proteins that can mimic antibodies in your immune system. Monoclonal antibodies can stimulate or change your immune response to clear cells that cause disease or carry medicine to treat disease. 

For those with Alzheimer’s, a protein called beta-amyloid collects between brain cells and disrupts their function. Researchers are investigating if monoclonal antibodies, including lecanemab, could prevent these plaques from forming, or help the body clear them from the brain. 

Lecanemab is being studied in a double-blind phase 3 randomized controlled trial (the gold standard of medical research). These types of studies are designed to evaluate adverse effects of a new drug and whether it offers a treatment benefit.

The lecanemab trial took place at 235 locations in North America, Europe, and Asia, and included 1,795 participants with early-stage Alzheimer’s. In the U.S., the study was designed to represent the real world: 4.5 percent of participants were Black, and 22.5 percent were Hispanic. The people included in the trial were randomly placed into two groups: one group received lecanameb through intravenous infusion (IV) every two weeks, and the other group was given a placebo, or a “dummy” treatment that appears like the drug but has no therapeutic effect.

After 18 months, the trial showed that compared to placebo, lecanemab was associated with significant reductions in beta-amyloid plaques. The study’s results, which were published on November 29 in the New England Journal of Medicine, also found the drug was associated with:

  • 27 percent slower rate of cognitive decline
  • 31 percent lower risk of progressing to the next stage of Alzheimer’s
  • 37 percent slower decline in activities of daily living
  • Better maintenance of health-related quality of life
  • Less wear and tear on caregivers

Given these early promising results (and the lack of alternatives for people with Alzheimer’s), lecanemab, received accelerated approval by the FDA in January 2023. The FDA’s accelerated approval program allows for early approval of drugs that treat a serious condition and “fill an unmet medical need.” The drug has now received full FDA approval, which means that more patients may gain access to the drug through Medicare coverage. But lecanemab has also sparked some controversy due to its high cost and safety concerns.

Lecanemab’s safety and cost concerns

Despite encouraging early results, adverse events among those who received lecanemab were common.  Almost 27 percent of participants developed amyloid-related imaging abnormalities, known as ARIA, compared to 9 percent who received placebo.

When the plaques that have accumulated along the blood vessels in the brain are pulled away by anti-amyloid antibody therapy, it can weaken the blood vessels, Hascup explains. That can result in fluid accumulation, swelling, and microscopic bleeding in the brain—a complication dubbed ARIA when it is detected on brain MRI.

ARIA most often develops at the beginning of treatment. Symptoms may include fatigue, headache, confusion, dizziness, falls, vision change, or nausea. But about 77 percent of people with ARIA and fluid accumulation in the brain do not have symptoms. In most cases (88 percent), this resolves on its own without long-term problems. Rarely, ARIA with microscopic bleeding may result in larger bleeding into the brain or stroke. People with underlying disease in the small blood vessels of the brain may be at increased risk for this more serious issue.

In the lecanemab trial, most ARIA were detected within the first three months of treatment. Almost 13 percent of people who received lecanemab developed ARIA with fluid accumulation, and just 2.8 percent of these people showed symptoms. ARIA with fluid accumulation resolved within four months in 81 percent of these people. About 17 percent of people who received lecanemab developed ARIA with microscopic bleeding and just 0.7 percent of these people showed symptoms.

Two people who received lecanemab died from large bleeding into the brain, compared to one person in the placebo group. In response, Biogen issued a statement, noting that in its assessment the deaths could not be attributed to lecanemab. These two people on lecanemab who died had other underlying health problems and were taking blood thinners, which could have contributed to their deaths, the company said. A third death was also reported, but circumstanced surrounding the death are unclear.

“All the available safety information indicates that lecanemab therapy is not associated with an increased risk of death overall,” Essai added in a November 29 statement.

But critics argue, these safety concerns may not outweigh the drug’s possible benefits. “Considering lecanemab is for people in the early stages of dementia who are still high-functioning, these adverse events could worsen their quality of life,” Hascup says.

Lecanemab did not actually cure Alzheimer’s—only slow its progression. And the difference between lecanemab and placebo on a standard scale that assesses cognitive symptoms in dementia suggests it may not necessarily make a very notable difference in people’s lives.

“What is important to keep in mind is that patients receiving lecanemab still experienced a decline in their memory, judgment, and quality of life—just to a lesser extent than those receiving placebo,” Hascup explains. “The modest improvement of someone on lecanemab may be overshadowed by the progressive nature of the disease when viewed through the lens of a caregiver or loved one.”

Another potential pitfall is that monoclonal antibodies are not always easy to administer. Most require traveling to a healthcare facility for an IV infusion and monitoring for potential reactions. And they can be costly and difficult to produce on a large scale. For the millions of people with Alzheimer’s, that raises questions of affordability and availability.

In addition, many people are diagnosed after the disease has progressed and may not benefit from a drug that needs to be started early before the damage has been done. Better ways of identifying Alzheimer’s earlier may be needed to fully benefit from a drug like lecanemab.

Patients and their families may need to carefully weigh these risks and benefits with their healthcare providers (HCPs) before starting treatment, Hascup adds.

The debate over the amyloid hypothesis

Accumulation of beta-amyloid plaque is thought to be toxic to brain cells and lead to dementia. For two decades, this amyloid hypothesis has been the prevailing theory for the root cause of Alzheimer’s, according to Hascup. Many drug developers have gone this route, but this theory has yet to be proven and scientists remain divided. Some researchers question whether targeting amyloid is the best way to go.

One problem is that the field is littered with clinical trials of anti-amyloid drugs that failed to improve clinical symptoms. At least one major pharmaceutical company, Pfizer, gave up altogether and stopped developing new drugs for Alzheimer’s in 2018.  Just last year, the FDA approved another anti-amyloid monoclonal: Biogen’s aducanumab. It was a controversial decision, based on research suggesting aducanumab decreased amyloid but without clear evidence that it improves cognitive symptoms in Alzheimer’s.

The string of failures has led some to argue that the amyloid hypothesis is wrong. Others believe the trials have design flaws because they include people who have already begun to show symptoms of Alzheimer’s. They liken Alzheimer’s to a slow burn, with the damage caused by amyloid starting many years before symptoms start. To reap the benefits, anti-amyloid therapy would ideally need to start as early as possible. Once symptoms start, the damage may be too extensive to halt or reverse the process.

Newer evidence that decreasing amyloid with lecanemab may slow cognitive decline when treatment is started early enough could help settle this debate.

In the meantime, the director of the NIH’s National Institute on Aging Richard J. Hodes, MD, also issued a July 2022 statement, acknowledging the disappointing results from recent clinical trials of anti-amyloid drugs. Dr. Hodes noted, however, that there is still a “strong scientific” rationale for continuing to explore anti-amyloid therapy, as well as other causes of Alzheimer’s. As a “complex disorder,” Alzheimers has many contributors, such as other proteins besides amyloid, inflammation, genetics, fat droplets, environmental factors like infections or pollutants, and changes to the blood vessels in the brain, he wrote.

Where does Alzheimer’s drug development stand now?

As of January 2023, there were 187 clinical trials assessing 141 different treatments for Alzheimer’s. Of these, 79 percent are drugs aimed at changing the course of the disease.

Six anti-amyloid therapies are already in phase 3 clinical trials. Indianapolis-based Eli Lilly published results for its monoclonal donanemab in May 2023. The drug was shown to significantly slow cognitive and functional decline in people with early symptomatic Alzheimer's disease. Based on these results, Lilly plans to move forward with global regulatory submissions as quickly as possible and expect to submit to the FDA for approval in the coming weeks.  

Scientists are also exploring therapies designed to treat other possible causes of the disease. Among clinical trials for drugs aimed at changing the course of Alzheimer’s, about 11 percent are investigating drugs that could help clear tau protein, which accumulates and forms toxic tangles that are typically found in later stage Alzheimer’s disease patients, Hascup says. Some researchers think tau protein more strongly correlates with cognitive decline.

Other treatments undergoing clinical trials include those that reduce inflammation, improve brain metabolism, or restore chemical signaling. Hascup suggests, however, that multi-drug therapy may be the best bet in the long run. “Combination therapies based upon an individual’s amyloid or tau burden may provide even better therapeutic benefits,” he says.

Scientists are also working on an anti-amyloid vaccine. In November 2021, researchers at Brigham and Women’s Hospital in Boston launched the first human trial of an Alzheimer’s nasal vaccine. It uses an innovative approach that stimulates immune cells in the brain to clear amyloid. It’s a spray that could be easy to administer, have fewer side effects, and could be more widely available for millions of people with Alzheimers. Researchers think it may have the potential to prevent Alzheimer’s—not just treat the disease.

The best prevention now, though, is to “do everything our mothers told us all those years ago,” Hascup says. “Eat a healthy diet, stay active, spend time with your friends, never stop learning, and get a good night’s sleep. The earlier in life you practice these habits the better chance you have at reducing your dementia risk.”

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