Lecanemab, an Alzheimer's Drug, Approved by FDA Despite Safety Concerns

The US Food and Drug Administration (FDA) has given the green light to lecanemab, a treatment for Alzheimer's disease that targets the underlying cause of the condition and aims to slow cognitive decline. While researchers are pleased with the approval, the news is overshadowed by reports of patient deaths and allegations that the FDA acted improperly in approving the first such drug last year.

Lecanemab, which will be marketed under the name Leqembi, is the first Alzheimer's treatment to slow cognitive decline in a clinical trial and the second to be approved within the past two years. The drug, produced by biopharmaceutical companies Eisai and Biogen, is a monoclonal antibody that is intravenously infused and targets amyloid plaques in the brain that are believed to contribute to cognitive impairment and dementia in Alzheimer's. By slowing the progression of the disease in its early stages, lecanemab will allow individuals to live independently and participate in daily life for a longer period of time, according to Joanne Pike, president and CEO of the Alzheimer's Association in Washington, DC. Eric Reiman, executive director of the Banner Alzheimer's Institute in Phoenix, AZ, added that the findings offer hope for patients and their families, as well as a promising step in the development of effective ways to modify and prevent the clinical onset of the disease.

Unclear impact

Lecanemab received authorization under the FDA's 'accelerated approval' pathway, which is reserved for therapies for diseases that have few treatment options and does not require phase III clinical trial data. However, researchers are optimistic about the phase III data for the drug, published in November 2022, which was produced by Biogen and Eisai. The trial, involving approximately 1,800 people with early-stage Alzheimer's, demonstrated that the antibody slowed cognitive decline by 27% over 18 months of treatment.

The FDA's decision to approve lecanemab was based on phase II data submitted by Biogen and Eisai, rather than the more recent phase III study results. The phase II study showed that lecanemab reduced plaques in the brains of 856 patients, but did not evaluate whether this had any effect on their cognitive abilities. This is the same pathway that was used to approve aducanumab, a similar antibody also produced by Biogen and Eisai. It is not clear what impact the 27% decline in cognitive decline seen in the phase III trial will have on the lives of people with Alzheimer's or whether this effect will be sustained after 18 months. Eric Reiman, executive director of the Banner Alzheimer's Institute in Phoenix, AZ, suggested that it could mean "an extra six months of recognizing a loved one's face or performing a valued activity," but added that further research is needed to confirm this. In the meantime, the FDA has stated that lecanemab should only be used for individuals with mild cognitive impairment, the same group as in the clinical trials.

Treatment risks

Diana Zuckerman, president of the National Center for Health Research in Washington D.C., has expressed doubts about whether the benefits of lecanemab outweigh the risks for patients. "You're dealing with people with mild cognitive impairment who are functioning and you're putting them at risk," she said, referring to both the potential health risks and the financial cost of treatment. Eisai has stated that a year of lecanemab treatment will cost $26,500 in the United States.

In recent months, it has been reported that three people enrolled in the phase III trial of lecanemab died during the extended phase of the trial, when patients receiving placebo could request to be given the drug. The cause of death was complications involving brain bleeding and seizures. Some researchers believe that these deaths may have been caused by a condition known as amyloid-related imaging abnormalities (ARIA), which may have resulted from the lecanemab antibody weakening blood vessels in the brain as it targeted amyloid plaques. It is worth noting that all of the patients were taking anticoagulant medications at the time, which may have exacerbated the bleeding.

The approval of aducanumab, a monoclonal antibody also used to treat Alzheimer's disease, has caused controversy due to doubts about its effectiveness in improving cognitive decline. The FDA's own scientific advisory panel opposed the approval of the drug in a vote of 8-1, and three members even resigned in protest after the FDA went ahead with the approval. This has raised questions about the FDA's decision to also approve lecanemab, as it did not hold a public advisory meeting before granting accelerated approval for the drug.

In aducanumab’s shadow

The approval of lecanemab, a treatment for Alzheimer's disease, has been met with skepticism due to concerns about patient safety and reports of the FDA acting improperly in the approval of a similar drug, aducanumab, last year. Lecanemab, made by Eisai and Biogen, slows cognitive decline in patients with mild cognitive impairment, but its approval was based on phase II data and not phase III data, which showed the drug slowed cognitive decline by 27% over 18 months of treatment. The approval of aducanumab, made by the same companies, was also granted through the FDA's accelerated approval pathway and was met with controversy due to a lack of strong evidence for its effectiveness. A congressional investigation found that the approval process for aducanumab was "rife with irregularities" and raised concerns about the FDA's and Biogen's actions.