New Alzheimer's Drug: 4 Things to Know About LecanemabJuly 24, 2023 - Katie McCallum
Alzheimer's disease currently ranks as the sixth leading cause of death in the U.S. and estimates suggest that some 6 million Americans, mostly older adults, are currently living with the disease, according to the National Institute on Aging. It's a devastating brain disease, one that robs people of their ability to remember, think and reason over time.
Medications to reduce Alzheimer's disease symptoms have been around since the 1990s, but actual treatments — ones aimed at rectifying the root cause of the disease — have lagged behind.
There's hope on the horizon, though. The FDA recently granted full approval to lecanemab (Leqembi) for the treatment of mild, early Alzheimer's disease or mild cognitive impairment caused by this disease. Targeting the disease process itself, this new Alzheimer's drug is the first of its kind to be fully approved by the FDA.
"It's the first drug that's been clearly shown to slow the progression of Alzheimer's disease," says Dr. Joseph Masdeu, a neurologist at Houston Methodist. "It's not a cure, and it can't stop or reverse the disease, but it can give a person more time — to be independent, to be with their family."
Lecanemab is also more promising and less controversial than aducanumab (Aduhelm), the predeccesor drug that received conditional approval from the FDA last year but hasn't been widely prescribed due to concerns over its effectiveness.
"For certain Alzheimer's patients, the data show that the clinical benefits of lecanemab outweigh the potential risks," says Dr. Masdeu. "It's this data that prompted the FDA to convert the accelerated approval granted in January to full, traditional approval."
In a clinical landscape that's long searched for answers, lecanemab is a sure step forward. But you likely have questions. Here are things that Dr. Masdeu says people will need to understand and consider.
How does lecanemab work?
There's still much to be learned about Alzheimer's disease. One thing that is known, however, is that abnormal build-up of certain proteins contributes to detrimental changes in the brain, ultimately causing loss of neural connections and brain tissue shrinkage. Two such proteins thought to be involved are beta amyloid and tau proteins. Lecanenab targets the former.
"The drug is a monoclonal antibody designed to target and reduce the amount of beta amyloid deposits in the brain" explains Dr. Masdeu. "It's administered as an infusion into a vein every other week."
In an 18-month clinical trial, lecanemab reduced cognitive decline by 27% — a somewhat modest, but still clinically meaningful result. The effectiveness of the drug was measured based on how well participants fared in six cognitive areas — memory, spatial orientation, judgment and problem-solving, community affairs, home and hobbies and personal care. Trial data also showed that lecanemab significantly reduces the buildup of beta amyloid in the brain, validating the mechanistic action of the drug.
Who is eligible to receive lecanemab?
Of the estimated 6 million adults with Alzheimer's disease, it's thought that only about one-sixth — around 1 million — are potential candidates for lecanemab. That's because the drug is only approved for use in adults with mild cognitive impairment (MCI) or mild dementia, with confirmed presence of beta amyloid deposits.
"This is early-stage Alzheimer's disease, where people are symptomatic, but the symptoms haven't substantially progressed," says Dr. Masdeu. "They need to have beta amyloid deposits in the brain, which we assess using PET imaging or a lumbar puncture."
It's also important to note that the roll-out of lecanemab may be slow and challenging in some areas, meaning not everyone who's potentially eligible will have easy access to the drug. PET imaging and MRI scans are needed prior to starting lecanemab; infusion centers are needed to administer the therapy; and periodic MRI scanning is needed to monitor a person during treatment.
"These are factors we're prepared for, but not all hospitals will be ready for this," adds Dr. Masdeu. "Some patients may struggle to gain access to this treatment depending on where they live."
What are the side effects of lecanemab?
Lecanemab's approval came with the FDA's strongest safety warning, so it's not surprising that the drug's potential side effects are in the spotlight.
The most common are headaches and infusion-related reactions — nausea, changes in blood pressure, flu-like symptoms.
"However, in about 15% of patients, amyloid-related imaging abnormalities (ARIA) occurred," says Dr. Masdeu. "They can be detected by MRI as brain swelling or tiny hemorrhages. The patient most often does not feel anything, but in 3% of the patients ARIA may cause headache, visual disturbances or confusion."
To help mitigate this, MRI imaging is used before treatment to evaluate for pre-existing ARIA. And since the majority who experienced ARIA while taking lecanemab were asymptomatic, Dr. Masdeu points to the importance of monitoring the brain during treatment.
"After a baseline MRI, we follow up with MRI scans before the fifth infusion to ensure no bleeding or swelling is present," explains Dr. Masdeu. "Scans are also needed before the seventh and 14th infusions. If abnormalities are seen on any of these scans, the severity will need to be taken into account when deciding whether to continue the drug or if treatment should be paused or even stopped altogether."
Despite these potential side effects, experts believe the benefits of lecanemab outweigh the risks for people with MCI or mild dementia.
How do you know if you should consider lecanemab?
With full approval, lecanemab is on track to be widely covered by Medicare. This matters since the drug reportedly costs more than $26,000 per year. People taking the medication will still face out-of-pocket expenses, but coverage means that most of those who are eligible should be able to afford it.
Still, lecanemab is a new drug — and one not devoid of risk — so you're likely wondering how to know if lecanemab is right for you or your loved one.
"This will be a conversation you will need to have with your neurologist," says Dr. Masdeu. "Not everyone with early Alzheimer's will be eligible. We need to confirm the presence of beta amyloid deposits. We need to carefully consider the risks of side effects for each individual. But we know that, for the right people, this drug can help slow progression of Alzheimer's disease, giving them more freedom for more time."
There are still unknowns, of course. How easy will it be for people to access lecanemab? How long will a person need to take it? Over time, could the treatment become more effective — or lose effectiveness? Will easier sites of administration — for instance, by an injection under the skin — be equally effective?
"This is just the start, but it's a good start," says Dr. Masdeu. "Everyone in the field is asking these questions and more. For instance, through a clinical trial of pre-symptomatic Alzheimer's disease, we're asking if lecanemab can prevent Alzheimer's disease. The hope is that we build from here, continuing to advance how we treat this disease."
Lecanemab isn't the only hope on the horizon for people suffering from Alzheimer's disease. The FDA is expected to make a decision about another new Alzheimer's drug, donanemab, by the end of the year.