Alzheimer’s Drug that Slows Down Cognitive Decline Approved by FDA

The Food and Drug Administration (FDA) of the United States has approved a novel drug to treat Alzheimer's disease in its early stages (1^✔ ✔Trusted Source
FDA Grants Accelerated Approval for Alzheimer’s Disease Treatment

Go to source). Lecanemab, which will be available under the name Leqembi, can slow the cognitive decline associated with Alzheimer’s disease by 27%, according to data submitted to the FDA by the drug’s developers, Eisai and Biogen. It is only the second medicine to show any improvement in neurodegeneration, which is a critical requirement in the FDA's approval evaluation.

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What is Lecanemab?

Lecanemab is one of the drugs that targets amyloid, a protein that builds up abnormally in the brains of people with Alzheimer’s. It works on a form of amyloid called protofibrils that are particularly toxic to brain neurons. The drug attaches to these pieces of amyloid, preventing them from clustering together to form the plaques that can compromise nerve function.

While the 27% improvement in cognitive test scores among the patients taking lecanemab compared to those receiving placebo over 18 months may not seem like a lot, it could slow decline enough to give patients months or even years of additional time with fewer memory problems.

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Side Effects of Lecanemab

The potential benefit for Alzheimer’s patients is tempered by some caution from experts about side effects related to the medication, including inflammation of the brain (which occurred in about 12.6% of people taking the medication in the studies) and bleeding in certain people. People who carry a genetic risk for Alzheimer’s in the ApoE gene are more vulnerable to the brain inflammation, known as ARIA (amyloid-related imaging abnormalities), which can be detected with regular brain scans and controlled with careful monitoring. The FDA’s approval includes a warning to doctors prescribing the drug about the risk of ARIA.

Several people involved in the drug’s trials have died, although researchers have not determined if lecanemab played a role in their deaths. The risk of bleeding was detailed most recently in a letter published in the New England Journal of Medicine by clinicians at Northwestern Feinberg School of Medicine. They described the case of a 65-year-old woman who had a genetic predisposition for Alzheimer’s and had participated in the Eisai study. She had a stroke after completing the 18-month study—during which it’s not known if she received lecanemab or placebo—and was participating in the next phase of the trial in which all participants received the drug. She had completed three doses when she came to the emergency room with signs of stroke. Brain scans confirmed that diagnosis, and she was treated with an intravenous blood thinner called tissue plasminogen activator. She later died (2^✔ ✔Trusted Source
Multiple Cerebral Hemorrhages in a Patient Receiving Lecanemab and Treated with t-PA for Stroke

Go to source).

Whether lecanemab contributed to the multiple brain bleeding events she experienced isn’t clear yet, and Ivan Cheung, CEO of Eisai Inc, says that the mortality among those receiving the drug in the studies is comparable to the rate among similarly aged people in the general population. But the case study highlights the importance of careful and considered prescribing of lecanemab for patients—especially those with genetic risk for Alzheimer’s, and those using certain medications to treat other conditions. This could potentially interact with the drug. Blood-thinning treatments were already known to interact negatively with anti-amyloid therapies like lecanemab.

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Why Lecanemab is Historic

Lecanemab is the second ‘disease-modifying’ drug approved by the FDA to treat Alzheimer’s, which means it addresses one of the features, which is amyloid of the disease. Other drugs used in Alzheimer’s patients, such as donepezil can minimize some of the memory symptoms of the condition but cannot slow the gradual decline of brain nerve function. The only other approved disease-modifying Alzheimer’s drug, aducanumab, which also targets amyloid, showed less definitive benefit among those taking it compared to lecanemab.

Experts say the extensive and rigorous studies conducted that led to the FDA’s decision may give doctors and patients more confidence that lecanemab can slow the degeneration of neurons typical of Alzheimer’s. However, it will be important to match the drug to the patients who are most likely to benefit. This includes those with early signs of Alzheimer’s related cognitive issues. “I think it will require a change in the way Alzheimer’s is identified and diagnosed. With a drug like lecanemab, it means physicians will have to evaluate for cognitive impairment earlier, and identify the cause of that impairment”, says Dr. Michael Irizarry, vice president of clinical research at Eisai Inc.

It is important to remember that the drug does not reverse damage to nerve function in the brain, but slows down the process driving the disease, so such screening could identify more people who could potentially benefit, and even lead to greater improvement over time. It would be interesting to see if patients continue receiving the treatment for a longer period of time, whether they will see even more benefit compared to people not being treated.

Lecanemab and Other Alzheimer’s Drugs are Still Under Study

Lecanemab was approved under FDA’s accelerated approval process, which allows the agency to approve drugs when there is an unmet medical need along with different standards than are usually required. This happens if early safety and efficacy information is compelling enough. In lecanemab’s case, Eisai’s robust phase 2 studies, which showed a 27% improvement in cognitive skills, were enough for the FDA to consider the company’s request for approval, even while the last phase 3 stage of testing continued.

The hope is that lecanemab’s success will spawn more effective anti-amyloid therapies, as well as other treatments. For example targeting proteins like tau, for example, which are also toxic in brain neurons, that in combination could hold off the most damaging processes of the disease. If these therapies are started earlier in the course of disease, before symptoms of memory loss or cognitive decline appear, it may be possible to avoid the devastating effects of neurodegeneration altogether.

The company is also conducting studies of lecanemab in people who are more vulnerable to developing Alzheimer’s, such as those with certain genetic risk factors, but have not shown signs of memory or other cognitive symptoms yet. The study will provide hints about whether it’s possible to delay or even prevent the disease altogether.

References:

1. FDA Grants Accelerated Approval for Alzheimer’s Disease Treatment - (https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-alzheimers-disease-treatment)
2. Multiple Cerebral Hemorrhages in a Patient Receiving Lecanemab and Treated with t-PA for Stroke - (https://pubmed.ncbi.nlm.nih.gov/36599061/)

Source-Medindia