On July 6, the U.S Food and Drug Administration (FDA) granted traditional approval to Leqembi® (lecanemab), a drug developed by pharmaceutical firms Eisai and Biogen to treat Alzheimer’s disease. This decision converts the accelerated approval Leqembi received in January, following a confirmatory trial that demonstrated verified clinical benefit.
“Up until now, no one considered this a treatable disease,” says Mary Sano, PhD, Professor of Psychiatry and Director of the Alzheimer’s Disease Research Center at the Icahn School of Medicine at Mount Sinai. The full approval of lecanemab marks an exciting chapter for treating Alzheimer’s disease, providing physicians with more options. Cognitive specialists at Mount Sinai are now offering lecanemab as a treatment.
Mary Sano, PhD, Director of the Alzheimer’s Disease Research Center at the Icahn School of Medicine at Mount Sinai
What is lecanemab and how does it tackle Alzheimer’s disease? How might a patient access it at Mount Sinai? Dr. Sano explains why this drug will make a big impact in treating this condition, which is all too common among the aging.
What is lecanemab?
Lecanemab is a monoclonal antibody treatment that’s designed to reduce amyloid beta plaques in the brain. It is delivered as an intravenous infusion, over approximately one hour, once every two weeks.
“It is widely accepted that amyloid beta is a defining agent for Alzheimer’s disease,” says Dr. Sano. While the causes of Alzheimer’s disease are not fully known, accumulations of amyloid beta and other proteins such as tau tangles have been observed in patients, and are hypothesized to cause memory and functional loss.
The drug has been approved for mild cognitive impairment (MCI) and mild dementia. Patients in this category are still able to perform daily tasks, such as driving or going to work, but might experience memory lapses, such as forgetting words or location of objects.
What does this drug mean for patients?
In the confirmatory clinical trial that helped lecanemab clinch its full approval, the drug showed a statistically significant reduction in cognitive decline compared to placebo.
What patients can expect is a slowing of cognitive and functional loss, says Dr. Sano. The outcomes measured in the study relate to instrumental activities that early-stage Alzheimer’s disease patients might struggle with—paying bills, banking, certain computer tasks.
“The demonstrated effect is modest, but it’s robust, seen across all measures,” she notes. Those benefits were seen at month three of treatment and persisted through month 18, at the end of the study.
“I don’t want to overstate that this is the be-all and end-all of treatment,” Dr. Sano adds. “I’m not telling you this is a huge effect and the person goes back to 100 percent normal. But until the lecanemab studies, we had other monoclonal antibodies and we’ve not seen such consistent benefits.”
How can I access lecanemab?
The Centers for Medicare and Medicaid Services (CMS) announced in early July that lecanemab is eligible for Part B coverage under Medicare. One of the requirements is documented evidence of amyloid beta plaque in the brain, which requires imaging.
“If you don’t have the presence of amyloid, this means this is a drug you cannot use, even if you are symptomatic with memory or other cognitive problems,” Dr. Sano says.
Side effects for lecanemab could include amyloid-related imaging abnormalities (ARIA), and take the form of either bleeding or swelling in the brain, or both. Some genetic factors, such as the apolipoprotein E (APOE) ε4 gene, may increase the risk of ARIA. Other factors, such as whether patients are on blood-thinning medications, should also be considered before accessing treatment. At Mount Sinai, each patient who is interested in lecanemab receives a personalized evaluation to determine eligibility and appropriate counseling.
There could be economic barriers to access, Dr. Sano notes. Lecanemab has been reported to cost $26,500 per year. Under traditional Medicare, patients could expect to pay a 20 percent copay for treatment, although that might be covered by a supplemental insurance plan. Eisai has also launched a patient assistance plan.
In addition to the drug, there are other associated costs, including positron emission tomography (PET) for amyloid imaging, infusion, and travel expenses. Coverage of those expenses depends on the insurance.
“We need to make sure underrepresented groups can access this treatment,” says Dr. Sano.
Will lecanemab change how we look at Alzheimer’s disease?
Prior to lecanemab, the prevailing view of patients diagnosed with MCI or mild dementia had been a wait-and-see approach, Dr. Sano says. Practitioners might be resistant to start an early-stage patient on active treatment, and similarly, patients who are highly functional might be reluctant to compromise their autonomy.
“There’s a barrier to changing our culture, but it’s clearly surmountable,” notes Dr. Sano. “The one difference we have to consider is this: people don’t stay in mild dementia forever. We need to change the culture to get this addressed early.”
What has lecanemab shown in clinical trials?
In a placebo-controlled, double-blind randomized study of 1,795 people, lecanemab showed a statistically significant and clinically meaningful reduction in decline of the Clinical Dementia Rating (CDR), a cognitive and functional measure based on patient and caretaker reports and the trial’s primary outcome. Key secondary outcomes included measurements of change in amyloid beta and other cognitive scales and measurements of daily living capabilities.
Here are the efficacy and safety highlights:
- Lecanemab-treated patients demonstrated a 27 percent slowing of decline in CDR compared to those on placebo at 18 months.
- Statistical significance for CDR was seen starting as early as six months, with the difference from placebo widening every three months.
- On a 100-point Centiloids scale, with 0 being a patient with no amyloid beta and 100 being the average amount of plaque a mild-to-moderate Alzheimer’s disease patient might have, the lecanemab group saw reduced plaque burden of 55.5 at 18 months, whereas the placebo group saw an increase of 3.6.
- Statistical significance for amyloid burden was achieved starting at three months.
- The most common side effects in the lecanemab group were infusion effects, with 26.4 percent having experienced it. Of those, 96 percent were considered mild to moderate.
- Other side effects include amyloid-related imaging abnormalities—which could occur from amyloid-targeting therapies—as well as headaches and falls. Serious adverse events were reported in 14 percent of the lecanemab group and 11.3 percent of the placebo group.