The U.S. Food and Drug Administration (FDA) granted Leqembi accelerated approval on Jan. 6, 2023. It is the seventh drug the FDA has approved for the treatment of Alzheimer’s disease.
The generic name of the drug is Lecanemab. It has been developed by the Japanese company Eisai in partnership with the U.S. company Biogen. These are the same companies that developed the sixth drug for the treatment of Alzheimer’s disease, Aduhelm (generic name aducanumab).
Lecanemab Is the First FDA-Granted Anti-amyloid Drug to Improve Cognitive Function
The first five FDA-approved drugs are donepezil, rivastigmine, galantamine, memantine, and memantine combined with donepezil. These drugs can temporarily relieve symptoms. Patients may have some amelioration in cognitive function, but the underlying brain pathologies of Alzheimer’s disease cannot be reduced or stopped, and the course of the disease cannot be altered.
By contrast, Lecanemab and aducanumab are human IgG1 anti-amyloid monoclonal antibodies and can decrease the expression of pathological biomarker Aβ aggregation in early Alzheimer’s disease.
The difference between the two is that aducanumab does not result in cognitive improvement, while Lecanemab can moderately ameliorate cognitive decline in Alzheimer’s disease cases.
When the FDA approved aducanumab in 2021, the decision prompted many disagreements in the medical field. Some medical professionals claimed that the decision was made on the ability to remove Aβ plaques without supportive evidence of improving cognitive function. Others claimed there was insufficient data to approve the drug’s efficacy.
Lecanemab, on the other hand, had solid data to approve its effectiveness in reducing the rate of cognitive decline by 27% after an 18-month clinical investigation on 898 patients in the early stages of Alzheimer’s disease during the double-blind phase 3 clinical trial.
Lecanemab can both improve cognitive function and reverse the course of Alzheimer’s pathology.
This sounds promising, but a significant problem remains: whether Aβ aggregation is the cause of Alzheimer’s disease has been the subject of debate in the medical field.
At the same time, the side effects of Lecanemab are causing concerns.
Safety Concerns, Including Three Deaths
Though the first five Alzheimer’s drugs that the FDA approved could not fundamentally reduce the pathological changes of Alzheimer’s disease, they have relatively mild side effects, such as headache and nausea.
However, aducanumab is associated with a 40 percent increased risk of a serious condition called amyloid-related imaging abnormalities (ARIA), an indicator of brain swelling. Individuals receiving aducanumab should be monitored closely, so ARIA is quickly identified and safely managed.
In a study of Lecanemab, 20 percent of participants experienced an adverse event, such as swelling or bleeding in the brain, with symptoms of headaches, visual disturbances, and confusion.
So far, the treatment with Lecanemab during clinical trials has also been linked to three deaths.
One individual suffered a stroke before the treatment and received a blood thinner before receiving Lecanemab. A second death occurred when a woman suffered stroke symptoms after starting Lecanemab treatment, followed by a series of seizures; she died a few days later, and her doctor found massive bleeding in her brain.
On Jan. 4, two days before the FDA approved the drug, the third death was reported in the New England Journal of Medicine—a patient receiving Lecanemab was treated for acute ischemic stroke with tissue plasminogen activator and subsequently died from multiple cerebral hemorrhages.
The three deaths were all related to strokes, and the patients took blood thinner before or after Lecanemab treatment.
Though these cases are still under investigation, they suggest fatal brain hemorrhage could occur during treatment with Lecanemab.
For safety reasons, FDA approved that Leqembi should be initiated in patients with mild cognitive impairment or mild dementia, which is the same with the population in the clinical trials. The labeling on the drug also states no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied.
In the future, the FDA should address the balance of efficacy and safety of Lecanemab and keep an eye on adverse events. Longer trials are needed to explore the contraindications and side effects.