Another drug by the makers of Aduhelm (the newest Alzheimer’s medication, approved by the FDA in June 2021) is being tested and might also offer relief for people in the early stages of Alzheimer’s disease. It’s called lecanemab, and clinical studies show that it may slow the progression of the disease by reducing the buildup of harmful plaques between cells.
Lecanemab is a monoclonal antibody designed to attach itself to beta-amyloid and signal the immune system to attack. For people in the early stages of dementia, the reduction of beta-amyloid protein tangles can help with thinking and memory. Alzheimer’s disease is progressive, meaning it worsens over time, but researchers believe the progression can be slowed down if those harmful beta-amyloid plaques are reduced in the brain.
As the number of Alzheimer’s cases climbs above 6 million in America, new pharmaceuticals offer hope for treatment. The FDA has already begun working with lecanemab’s creators to speed up the process toward approval. For more on when lecanemab might become available to the public, see below.
Lecanemab claims that the treatment reduces the development of harmful beta-amyloid plaques in the brains of people with mild Alzheimer’s disease. Lecanemab cannot cure Alzheimer’s, but someone with the disease can potentially hold onto recognition, memories, and mental sharpness for longer periods by taking the medication.
The companies that make lecanemab, Eisai and Biogen, finished and published Phase 3 of clinical trials in the fall of 2022. The results have continued to be positive backing up the drug maker’s claim that this therapy helps prevent the breakdown of the brain and its functions that are associated with Alzheimer’s disease. These functions are called cognitive decline and allow us to interpret the world around us to be able to easily live independently. While the first symptom that is normally observed has to do with memory, it is present in all aspects of everyday life from recall to problem-solving. In a group of 1,795 Alzheimer patients, a double-blind study was conducted. That means that neither patients nor clinicians knew which half of the group was receiving the drug and the other half getting a placebo. The clinical study followed patients for 18 months after bi-monthly treatments. After a year and a half of studying patients and how their brains were functioning, it was found the group who took lecanemab had lost less brain function and their associated symptoms were milder.
Previously, in Phase 2, 856 people with mild Alzheimer’s disease were given either lecanemab or a placebo.
Tests during Phase 2 showed the following, compared to placebo:
– Those who received lecanemab had less amyloid-beta in their brains
– The progression of dementia symptoms slowed down
Placebos are like a sugar pill. Administering a placebo to half the people in the study gives researchers a comparison to see if the drug is working. And researchers can tell whether someone’s decline in memory and thinking is faster or slower than normal by using the integrated Alzheimer’s Disease Assessment Scale, which combines brain scans and tests including the Mini Mental State Exam with an evaluation of how well instrumental activities of daily living (IADLs) like using a phone or preparing meals can be performed.
Promising test results for lecanemab earned the drug a breakthrough therapy designation from the Food and Drug Administration in June 2021. This means lecanemab has shown enough promise that it was put on a faster track toward FDA approval, a process requiring time-consuming reviews of research and study data.
Researchers said there was an association in trial subjects between lecanemab and greater brain-volume loss (specifically in the hippocampus, which holds memories) than the subjects who took a placebo. Some subjects who took the drug also saw a higher rate of amyloid-related imaging abnormalities (ARIA, also called “cerebral edema”), which are associated with brain swelling.
Lecanemab is an antibody that sticks to clumps of amyloid-beta found in the brains of people with Alzheimer’s disease. The drug signals the immune system to attack those clumps and clear them out. More specifically, lecanemab is a protofibril antibody that was designed to attack beta-amyloid in the brains of mice and then, after promising results, modified to work similarly in humans with mild Alzheimer’s disease.
Amyloid-beta is a protein found in healthy brains, but people with Alzheimer’s disease have been shown to experience a significant buildup of these proteins around brain cells. The buildups turn over time into plaques that affect communication between cells. Before becoming plaques, however, amyloid beta in brains with Alzheimer’s collect into fibrils, which are smaller than plaques but can cluster together into plaques that appear on PET and MRI scans of people with the disease. It’s during that stage, before the plaques form, that lecanemab can target and help reduce the amount of beta-amyloid.
Compared to Other Alzheimer’s Medications
Lecanemab is made in part by the company Biogen, which grabbed headlines in June 2021 when their drug Aduhelm (generic name aducanumab) became the first Alzheimer’s drug to receive FDA approval in almost 20 years. Both lecanemab and aducanumab are administered intravenously. Aducanumab and lecanemab both target beta-amyloid, though in slightly different ways. A big distinction is obviously that aducanumab has achieved FDA approval and is available now, whereas lecanemab is waiting for tentative approval from the FDA in early January 2023. More information on aducanumab (brand name Aduhelm) is available at this link.
Other medications that specifically target Alzheimer’s disease and related dementias are cholinesterase inhibitors (brand names Aricept, Razadyne, and Exelon) and memantine (brand name Namenda). These medications are administered in pill form. Studies show they can help strengthen communication between brain cells, which improves symptoms like memory loss and slows down mental decline.
Medicare can cover cholinesterase inhibitors and memantine if they are prescribed by a doctor. Medicare has not announced yet whether aducanumab will be covered (though those with Medicare Part D and Medicare Advantage can probably get help with costs), and a decision on coverage for lecanemab is probably several years away.
Lecanemab completed the third stage of trials and published its results at the end of 2022. The Phase 3 study followed 1,795 participants who took either the experimental drug or a placebo. Throughout the trial, the participants who were given lecanemab instead of the placebo were effective in showing less loss of brain function and milder symptoms of Alzheimer’s. This was because this is the first drug to prove that the breakdown of brain cells that causes their death speeds up the disease. Scientists found fewer beta-amyloid protein clumps in the brain of patients who used lecanemab.
During Phase 2, lecanemab was tested for safety and effectiveness by giving 856 people with mild Alzheimer’s either the drug or a placebo. Researchers saw a reduction of beta-amyloid in the brains of those who took lecanemab, as well as a slower progression of the disease.
The positive results that continue to come from the clinical trials of lecanemab have given the drug a fast-track designation with the FDA because it would be the first kind of therapy that focuses on preventing the breakdown of beta-amyloid proteins in the brain. Fast tract designations are given to drugs when there is nothing else on the market to treat an ailment or disease. Besides backing up scientists’ theories into how to slow the progression of Alzheimer’s, these positive clinical results are leading to the drug becoming available to the general public much more quickly. It is said that when the FDA reconvenes on January 6, 2023, they are going to decide if they will give lecanemab conditional approval. That means it can be available to be produced and marketed to the public while doctors, clinicians, and other healthcare professionals continue to study the drug’s effects over a longer time to asses effects and safety.
The new data and governmental approval decisions are not new for this drug. They began in June 2021, when the Food and Drug Administration granted it the “breakthrough therapy” designation. The FDA considers breakthrough therapies to have shown significant progress, or demonstrated they can help a significant number of people with an important illness. Earning breakthrough therapy status means the process of reviewing the drugs can be sped up.