Donanemab and Lecanemab for Early Alzheimer’s: What You Need to Know

Kisunla and Leqembi both slow the progression of early-stage Alzheimer’s disease, but there are some differences.

People who have been diagnosed with early-stage Alzheimer’s disease now have two drugs to choose from — donanemab (Kisunla) and lecanemab (Leqembi) — that can slow the progression of symptoms by targeting processes in the brain that are associated with cognitive decline. 

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Both medicines are what’s known as anti-amyloid antibodies, which are designed to clear the brain of plaque deposits that contribute to the symptoms caused by Alzheimer’s disease. Donanemab just won approval from the U.S. Food and Drug Administration (FDA) this month, a year after the FDA granted full approval for lecanemab. 

“These two medications are the first FDA-approved drugs in over 20 years for Alzheimer’s disease,” says Jared Brosch, MD, an associate professor of clinical neurology at the Indiana University School of Medicine in Indianapolis.

More importantly, these are the first drugs that go beyond symptom management to actually help the body remove plaque that damages the brain in Alzheimer’s disease, Dr. Brosch says. “The fact that we can impact the underlying pathology is a major breakthrough,” Brosch says. 

Can These Drugs Prevent Alzheimer’s Disease?

“It’s the million-dollar question,” says Lawrence Honig, MD, PhD, a neurologist at NewYork-Presbyterian Columbia University Irving Medical Center in New York City. 

Nobody knows the answer yet, Dr. Honig says. Clinical trials are underway to test these medicines in people who are cognitively healthy but have some early evidence of beta-amyloid plaques accumulating in their brains. These are people who don’t have any symptoms yet, and the trials are looking at whether these drugs can halt amyloid buildup in the brain and prevent cognitive decline caused by Alzheimer’s disease, Honig says.

It will take many years to fully answer this question, because people can develop plaque in their brain roughly two decades before they experience any cognitive symptoms, says Howard Fillit, MD, a cofounder and the chief science officer of the Alzheimer’s Drug Discovery Foundation in New York City. 

“Right now, we can easily identify people who have plaque in their brains before they develop symptoms,” says Dr. Fillit. “The future hope is that we can start them on medication that prevents or substantially delays the onset of Alzheimer’s.”

Who Should Take These Drugs?

Because these medicines work by clearing beta-amyloid plaques from the brain, people should take them only when lab tests show evidence of amyloid accumulation, Honig says. Typically, people will either get a positron emission technology (PET) scan of the brain or a spinal fluid test to look for evidence of amyloid. 

“Both drugs are only designed for and only valuable in people with Alzheimer’s,” Honig says. “If people have cognitive decline caused by something else, the drugs won’t work.”

In addition, the medicines are approved only for adults with early-stage Alzheimer’s disease. They aren’t designed to reverse cognitive changes that have already happened, so they won’t provide much help to individuals with advanced disease.

“These drugs are not meant to improve,” Brosch says. “They are meant to slow the disease down and preserve what functioning is currently available.”

What’s the Process for Taking These Drugs?

The first steps to taking these medicines require a formal Alzheimer’s disease diagnosis. 

Many people can start by seeing their primary care provider to see if their symptoms are consistent with early Alzheimer’s, Honig says. After that they may see a neurologist and get a magnetic resonance imaging (MRI) scan to examine the structure of the brain, followed by either a PET scan or a spinal fluid test to look for evidence of amyloid accumulation. 

Patients may also get a genetic test for a variation in the APOE gene that can increase their risk of cognitive decline, as well as their risk of rare, but serious, side effects from these medications. 

Both medicines are administered via infusions at a clinic or doctor’s office. Kisunla infusions are monthly, while Leqembi infusions are every two weeks. Each visit for infusions typically takes about two hours, Brosch says. 

What Side Effects Can Happen With These Drugs?

The most common side effects with both drugs can include infusion site reactions (causing pain or swelling) or relatively mild issues like headaches or nausea that resolve within a day or two, Honig says.

Amyloid antibody drugs also carry the risk of what’s known as ARIA, or amyloid-related imaging abnormalities. ARIA shows up on brain scans and can sometimes involve seizures or potentially life-threatening brain swelling or bleeding, although many people don’t experience symptoms.

“It is important to note that these brain changes usually remain asymptomatic and, on many occasions, will resolve by themselves,” says Jacobo Mintzer, MD, a psychiatrist at the National Institute for Brain Health at the Ralph H. Johnson VA Health Care System and a professor at the Medical University of South Carolina in Charleston. 

How Should You Decide Which Drug to Take?

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Which drug makes the most sense may depend a lot on individual patients’ circumstances, Honig says. Some people may prioritize the convenience of fewer infusion visits, and opt for donanemab because it’s administered monthly, as opposed to going every two weeks for lecanemab. 

The drugs also work differently, even though they both attack beta-amyloid in the brain. Donanemab acts only against amyloid that’s clumped together in plaques, while lecanemab also fights smaller forms of beta-amyloid that are constantly being generated. This may make donanemab a better fit for long-term treatment, Honig says.

“They are relatively comparable, but each patient will have to discuss the pros and cons with their neurologist,” Honig says.