The Lamen

New Alzheimer’s drug claims to slow cognitive decline by 27 percent

A bar graph for the breast cancer rates among women of different ethnicities.

The new Alzheimer’s drug may be able to delay the inevitabilities of Alzheimer’s, but we are still far from a cure.

Photo: Pexels

Published on Jul 17, 2023

The Food and Drug Administration granted full approval to lecanemab (brand name Leqembi) for treating adults with Alzheimer’s disease this month — suggesting that the drug should be used for patients experiencing mild dementia.

Alzheimer’s is a progressive neurological disease that causes memory loss, language problems, changes in mood, and other forms of cognitive decline.

  • Alzheimer’s disease is the most common form of dementia, affecting an estimated 6.7 Americans aged 65 or above.
  • The risk of Alzheimer’s worsens with age, with the number of people having the condition doubling every 5 years beyond age 65.

Details: Lecanemab, manufactured by Japanese drugmaker Eisai and Biogen, is currently suggested to reduce the rate of cognitive decline in the early stages of Alzheimer’s disease.

  • Lecanemab isn’t a cure for Alzheimer’s disease but targets the beta-amyloid plaques that have been believed to cause the disease, slowing down the progression of dementia. No evidence suggests that it can reverse cognitive function lost due to Alzheimer’s disease.
  • Eisai announced in a press release that lecanemab’s annual cost with be $26,000, suggesting that is significantly below the “projected societal value” of $37,600.
  • The full approval of the drug may also indicate expanded coverage under Medicare, which previously paid only for patients in certain clinical trials.

Data-driven: A clinical trial of 1795 patients involved a lecanemab group and a placebo group, with the lecanemab group receiving 10 mg per kilogram of body weight of the drug intravenously once every 2 weeks.

  • Lecanemab slowed cognitive decline by 27 percent on average after 18 months.
  • The incidence of adverse events was 21.3 percent for those who received lecanemab compared to 9.3 percent who received a placebo.
  • The drug has also been tied to three patient deaths during the clinical trials, with reports of extensive brain swelling, bleeding, as well as seizures.

Side effects: While patients experiencing side effects may not have some obvious symptoms, people being treated with lecanemab would require regular brain scans to rule out possible swelling of the brain.

  • According to the clinical trial, infusion-related reactions (with flu-like symptoms) were observed in 26.4 percent of the participants, and amyloid-related imaging abnormalities with edema or effusions in 12.6 percent.
  • Serious adverse events occurred in 14 percent of the lecanemab group, with common adverse events being cerebral microhemorrhages, superficial siderosis, headaches, and falls.
  • The FDA states that people may also experience confusion, dizziness, vision changes, nausea, and seizures.

Expert opinions: Science has searched for an effective treatment for Alzheimer’s for a while and previously promising drugs have flamed out, which raises concern over this new approval. Both patients and doctors are skeptical about the future of lecanemab, especially due to its high price and the extensive patient testing it implies.

Beta-amyloid plaques and Alzheimer’s.

Succumbing to the cognitive decline that occurs due to Alzheimer’s disease can be an increasingly painful experience, but science is yet to decode what goes on inside the body causing such brain degeneration.

Alzheimer’s disease is not an inevitable consequence of aging, even if the two factors may be deeply correlated — with the prevalence of AD doubling every 5 years after age 65. The most widely hypothesized cause behind the disease are growths in the brain known as “beta-amyloid plaques.”

These plaques are toxic clumps of beta-amyloid proteins that multiply and stick together, forming insoluble plaques that block intercellular signaling and trigger inflammation — disrupting normal cellular functions. While these plaques physically change the brain, these alone aren’t what lead to the development of AD.

As Alzheimer’s disease progress with time, plaques, neurofibrillary tangles composed of tau proteins, and inflammation collectively result in irreversible neuronal damage and cognitive decline.

However, the amyloid hypothesis has recently also been on the receiving end of some controversy, as a report published in Science last year suggested that a 2006 study falsified some of the facts regarding a specific type of amyloid causing Alzheimer’s disease.

A visualization of the beta-amyloid plaques and tau protein tangles that form in the brain in Alzheimer's.

Two hallmark pathological features of Alzheimer’s disease are the accumulation of beta-amyloid plaques and tau protein tangles in the brain. The complex interplay of these rogue proteins has been known to disrupt synapses, cause inflammation of the brain, and eventually result in nerve cell death and severe dementia.

Image by National Institute on Aging

How does lecanemab work?

Lecanemab is a humanized monoclonal antibody that targets these beta-amyloid proteins that are known to aggregate to form plaques in the brain — believed to be one of the primary drivers of AD.

“The unusual thing about this drug is that it targets not only the amyloid plaques that are a hallmark of Alzheimer’s but also clumps of amyloid, called oligomers, that float around inside and between brain cells, along with protofibrils that share properties of both oligomers and plaques,” told neurologist Samuel Gandy to Scientific American.

The clinical trial suggested that while people getting lecanemab still experienced cognitive decline, it progressed 27 percent slower than those on a placebo.

Scientists suggest that drugs like aducanumab failed because they bind to amyloid protein after it clumps together to form plaques, whereas lecanemab interferes with them at an earlier stage, targeting the “protofibrils” of beta-amyloid — strands that have not yet aggregated to form plaques.

What’s next: Lecanemab can have some potentially life-threatening side effects, and the drug may also be less effective in slowing cognitive decline in women — with a supplementary appendix suggesting that the drug slowed cognitive decline in women by 12 percent compared to 43 percent in men.