What the FDA’s accelerated approval of a new Alzheimer’s drug could mean for those with the disease – 5 questions answered about lecanemab

The U.S. Food and Drug Administration approved the medication lecanemab, sold under the brand name Leqembi, on Jan. 6, 2023, through an “accelerated approval pathway” that fast-tracks promising clinical treatments for diseases in which there are no other currently effective options.

The Conversation asked James E. Galvin, a neurologist from the University of Miami School of Medicine who specializes in the study of Alzheimer’s disease and Lewy body dementia, to explain the drug’s clinical potential to help ease the suffering of the roughly 6.5 million Americans who live with Alzheimer’s.

Lecanemab is a monoclonal antibody that targets beta-amyloid, a naturally occurring protein that becomes toxic when it clumps together to form the characteristic plaques that accumulate in the brains of people with Alzheimer’s disease. The drug is given through intravenous infusions every two weeks.

Antibodies are Y-shaped proteins circulating in the blood that recognize and neutralize substances in the body that they see as foreign, such as bacteria and viruses. A monoclonal antibody is produced by cloning, or making a copy of, a single white blood cell so that all the offshoot antibodies are derived from the same cell and bind to one specific target. In this case, lecanemab binds only to beta-amyloid proteins.

Lecanemab binds to a particular form of beta-amyloid as it clumps, called a protofibril. Studies suggest this is the species of beta-amyloid that is both most likely to aggregate into plaques that disrupt cell functioning and to play a role in the development of Alzheimer’s disease.

Earlier trials of other monoclonal antibodies failed to demonstrate a benefit and had more side effects, possibly because they targeted forms of beta-amyloid either too early or too late in the aggregation process.

Potentially, yes, for people with early-stage Alzheimer’s disease. Medications such as lecanemab have the potential to interfere with the progression of Alzheimer’s disease by removing beta-amyloid from the brains of people who are suffering with it.

Two recent publications describe results from two different phases of clinical trials.

One study, published in early January 2023, reported the results of a phase 3 clinical trial that included 1,795 participants, half of whom received lecanemab and another half who didn’t. In that trial, treatment with lecanemab not only met all its clinical outcomes and safety requirements, but it also reduced the amounts of beta-amyloid measured in imaging tests and in the blood.

Researchers also saw reductions in the levels of tau – the protein responsible for the neurofibrillary tangles that accumulate inside the neurons in patient’s with Alzheimer’s. And they found reduced levels of other proteins that measure brain injury and degeneration. This suggests that lecanemab could potentially address the disease by targeting it through both direct and indirect pathways.

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