For almost two decades, people with Alzheimer’s disease had no new treatment options. In the 2020s, drugs called monoclonal antibodies received FDA approval for people in the earliest stages of Alzheimer’s disease.
The two drugs approved in the U.S. so far — Leqembi and Kisunla — are both infusion-based drugs designed to target beta-amyloid plaques that build up in the brain. Scientists think that these plaques, along with other problematic proteins, are the force behind Alzheimer’s progression.
While these drugs don’t stop the disease, they may slow cognitive decline, at least slightly. (Some clinicians are still skeptical that the benefits of either drug outweigh the risks.)
With these two next-gen Alzheimer’s drugs now available, doctors and patients will need to consider several different factors to understand whether monoclonal antibody is the right choice, and if so, which of the two options is a better fit. Here are the points to consider.
1. Side effects
Both Leqembi and Kisunla have side effects, including brain swelling and brain bleeds (called amyloid-related imaging abnormalities, ARIA), and brain shrinkage. These risks tend to be higher for people with the genetic biomarker of Alzheimer’s: ApoE4. There can also be a higher risk if someone is on anticoagulant drugs.
ARIA (tiny brain bleeds)
Approximately 20 percent of people taking Leqembi develop ARIA. Among them, 15 percent will develop brain bleeds (ARIA-H), while 11 percent develop brain swelling (ARIA-E).
Comparatively, the risk of ARIA is higher for Kisunla. Twice as many people may develop ARIA, with 30 percent developing ARIA-H and 25 percent developing ARIA-E. People who have two copies of the ApoE4 Alzheimer’s risk gene are more likely to develop ARIA.
Most of the time, ARIA is asymptomatic. Doctors can spot ARIA during a brain scan and will wait for two to four months for symptoms to clear. However, in rare cases, it leads to serious symptoms, disability, and death.
Other side effects
As with any other drug administered by infusion, there is a risk of infusion-related reactions. One in four people who take Leqembi and about one in 11 who take Kisunla develop these reactions, which are often mild.
The symptoms of infusion-related reactions include:
- Fever and flu-like symptoms
- Nausea or vomiting
- Dizziness or lightheadedness
- Changes in heart rate and blood pressure
- Difficulty breathing or shortness of breath
In rare cases, some people who take Leqembi or Kisunla develop an allergic reaction that causes facial swelling, hives, and difficulty breathing.
2. How often is the drug taken?
Both drugs require people to travel to a specialized clinic for an intravenous infusion.
Leqembi requires bi-weekly drug infusions, while Kisunla requires monthly infusions. While a Leqembi infusion takes about an hour, a Kisunla infusion only takes 30 minutes. After 18 months of treatment, people receiving Leqembi are titrated to a lower dose and receive an infusion once every four weeks.
Kisunla, on the other hand, comes with stoppage instructions. When beta-amyloid is cleared below a minimal level, as measured by an amyloid PET scan, the doctor can take the patient off the drug. In some cases, people might only need to take the drug for six months before all the plaques are cleared from their brains.
3. Cost and insurance coverage
The dosage of Leqembi and Kisunla depends on weight. People who are heavier will require a higher dosage, increasing the cost.
Leqembi costs $26,500 for a person weighing the approximate average adult human weight of 165 pounds. It’s now covered by Medicare. Many private insurers don’t think the drug’s benefits are worth it and don’t cover it.
Kisunla is notably more expensive than Leqembi year over year ($32,000 compared to $26,500), but the total cost to a patient and/or their insurer will depend on how long patients stay on it. For example, if it takes six months to clear plaques, the drug would cost $12,522. However, it could run as much as $48,896 for a year and a half. Medicare covers Kisunla, but some private insurers might not think the benefits are worth it and decline to cover it.
