The Food and Drug Administration recently approved a drug that may help patients in the early stages of Alzheimer’s by slowing down the progression of the disease. In clinical trials, the drug, called lecanemab, reduced the rate of cognitive decline among participants.
But doctors and health experts are divided on whether it warranted an accelerated FDA approval. While some of them have praised the agency’s decision, describing the drug as groundbreaking, others are skeptical about whether it provides a substantial benefit.
In the U.S., over 6 million people are living with Alzheimer’s, an incurable and fatal disease that affects the brain and causes loss of cognitive function over time. While there are available medications that can treat Alzheimer’s symptoms, there have been no treatments that address the underlying cause of the disease. This is why some doctors have welcomed the accelerated approval of lecanemab. The FDA is likely to consider a full approval later this year.
“We’re pretty excited that we finally have something,” Dr. Reisa Sperling, who directs the Center for Alzheimer Research and Treatment at Brigham and Women’s Hospital in Boston, recently told NPR.
Heather Snyder, vice president of medical and scientific relations at the Alzheimer’s Association, told Yahoo News that the organization “celebrates” the Jan. 6 approval of the drug. “This is now the second approved treatment that evidence suggests changes the course of Alzheimer’s disease in a meaningful way,” she said.
Lecanemab, which will be marketed as Leqembi, is the second Alzheimer’s drug to receive a fast-track approval by the FDA. This accelerated authorization is usually given to promising treatments targeting diseases for which there are no other effective options available. In the summer of 2021, the agency gave a similar drug — aducanumab, sold under the brand name Aduhelm — accelerated approval as well. But the move was controversial because the FDA approved the drug despite conflicting evidence about whether it provided a benefit to patients, and against the recommendation of one of its committees of outside experts.
Aduhelm’s accelerated approval prompted a congressional investigation. Since then, the federal Medicare program has decided not to cover Aduhelm treatment for the general population, but only for patients who were enrolled in the clinical trial. Some hospital systems across the country have also declined to offer the drug to Alzheimer’s patients. Due to the controversy surrounding the drug’s efficacy and its high price, as well as the negative publicity it has received, few patients have received it. As a result, many doctors who treat the disease have been left, once again, with limited options.
Snyder said that even though Leqembi is not a cure, the fact that it may slow the progression of the disease would give patients more time to enjoy aspects of daily life.
“That could be things like participating in a birthday party, or going to a wedding, recognizing their spouse, their children, their grandchildren, their neighbors, and really that time is enabling an individual to also make decisions about their care as they go forward as well,” she said.
Like Aduhelm, lecanemab was developed by Eisai in partnership with fellow drugmaker Biogen. These treatments are monoclonal antibody therapies that are designed to remove a substance called beta-amyloid from the brain. Beta-amyloid is a naturally occurring protein that becomes toxic when it clumps together and forms the sticky plaques that are a hallmark of Alzheimer’s disease.
The theory behind the development of monoclonal antibody treatments like lecanemab is that amyloid plaques cause the loss of brain cells that leads to cognitive decline in people who suffer from Alzheimer’s. By reducing the amount of amyloid plaques in the brain, these treatments are believed to help slow the process of memory loss and cognitive decline.
In a clinical study of nearly 1,800 people in the early stages of Alzheimer’s, those who were given lecanemab for 18 months experienced 27% less decline in memory and thinking compared with those who received a placebo. Although the trial results were positive and unprecedented, some experts believe the excitement for the drug is not proportional to its apparent benefit.
“The clinical trial data shows a statistically significant but clinically undetectable difference in the outcome measure between active treatment and placebo over 18 months,” Dr. Michael Greicius, a professor of neurology and neurological sciences at Stanford University, told Yahoo News.
He said the accelerated FDA approval of lecanemab made sense because in clinical trials the drug showed that it can affect a biomarker associated with a disease. In this case, that biomarker is the reduction of beta-amyloid in the brain. “Lecanemab definitely removes amyloid plaques,” Greicius said.
But some experts fear that the approval of lecanemab will incentivize drug companies to focus on therapies targeting amyloid plaques while neglecting other treatment approaches that may be more fruitful.
“I do consider it a game changer, but in a negative sense, for how it will change the clinical and research landscape around Alzheimer’s disease,” Greicius said.
The new drug, which is administered through intravenous infusions every two weeks, is costly. The companies that develop it have said it will be priced at $26,500 per year. So far, the Centers for Medicare and Medicaid Services (CMS) has said it will not cover the drug, and unless lecanemab receives full FDA approval, that isn’t likely to change.
“What CMS is doing by restricting coverage for approved treatments is unprecedented,” Snyder said. “It’s not something we’ve seen before, and it’s wrong.”
If CMS ultimately decides not to cover lecanemab, Greicius said, the drug will likely be used, but not very widely, as it would have to be paid for out of pocket.
He noted that there are some safety concerns about lecanemab that need to be considered, particularly a condition that can occur with most other drugs that remove amyloid plaques from the brain, known as ARIA, or amyloid-related imaging abnormalities. Two forms of ARIA involve brain swelling and bleeding.
In the lecanemab study, more than 12% of people who received the drug experienced swelling of the brain, and more than 17% had bleeding. While few participants experienced complications, there have been at least three deaths linked to the drug, though those patients appear to have had additional risk factors.
But Snyder said these side effects should not be a reason for doctors and patients in the early stages of the disease not to consider the medication.
“It’s really important to remember this, Alzheimer’s is fatal … and all treatments have side effects,” she said. “So it’s important that we manage those and we understand them, and an individual should weigh any treatment decision — not just with this medication or this disease, but across the board — be able to weigh the potential benefits and risks [in] conversation with their clinician.”