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Alzheimer's Drug Lecanemab Gets FDA Approval Despite Concerns

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Officials at Alzheimer’s organizations praised the approval of the medication lecanemaab. Manu Padilla/Stocksy United
  • A new Alzheimer’s drug, lecanemab, has received accelerated approval from federal regulators.
  • The approval comes after the medication showed promise in slowing cognitive decline in a phase 3 clinical trial.
  • There are reports that three people died while taking the drug during the trial.
  • Some experts have said lecanemab may simply reduce symptoms and not improve brain function.
  • Nonetheless, officials at numerous Alzheimer’s organizations hailed the approval as an important and encouraging milestone.

A new drug to treat Alzheimer’s disease received accelerated approval today from the federal Food and Drug Administration (FDA).

FDA officials said the approval “represents an important advancement in the ongoing fight to effectively treat Alzheimer’s disease.”

“Alzheimer’s disease immeasurably incapacitates the lives of those who suffer from it and has devastating effects on their loved ones,” said Dr. Billy Dunn, the director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, in a press statement. “This treatment option is the latest therapy to target and affect the underlying disease process of Alzheimer’s, instead of only treating the symptoms of the disease.”

The drug, lecanemab, will be sold under the brand name Leqembi.

Some experts have questioned its effectiveness, but the medication showed promise in a phase 3 clinical trial.

Researchers said lecanemab slowed cognitive and functional decline by 27% when given to people with Alzheimer’s in the clinical trial.

The study results were published in late November in the New Journal of Medicine.

However, the journal Science reported in late December that three people died while taking the drug during the clinical trial. The journal reports that the third death was a 79-year-old Florida woman who died in mid-September after developing brain swelling and bleeding.

Her death, which happened during an extension of the clinical trial, was not reported in the November study results.

Reaction from Alzheimer’s organizations to lecanemab approval

The FDA’s approval of lecanemab was met with praise from officials at several Alzheimer’s organizations.

“The Alzheimer’s Association welcomes and celebrates this action by the FDA. We now have a second approved treatment that changes the course of Alzheimer’s disease in a meaningful way for people in the early stages of the disease,” said Joanne Pike, DrPH, the president and chief executive officer of the Alzheimer’s Association.

“By slowing progression of the disease when taken in the early stages of Alzheimer’s, individuals will have more time to participate in daily life and live independently,” she added. “This could mean more months of recognizing their spouse, children, and grandchildren. This could also mean more time for a person to drive safely, accurately and promptly take care of family finances, and participate fully in hobbies and interests.”

The reaction was equally positive from the Alzheimer’s Drug Discovery Foundation (ADDF).

“Today’s news is incredibly important and a source of optimism not only for patients but also for the medical and research community,” said Dr. Howard Fillit, the co-founder and chief science officer of the ADDF, in a press statement. “It shows us that our years of research into what is arguably the most complex disease humans face is paying off and it gives us hope that we can make Alzheimer’s not just treatable, but preventable.”

However, Fillit also issued a caution.

“This is encouraging news, but the approval of lecanemab is just the first step,” he said. “Alzheimer’s therapies will only be beneficial to patients if the right drug is given to the right patient at the right time based on their unique disease pathology, and for that, we need new and novel diagnostic biomarkers.”

Pike added that insurance coverage will also be an important hurdle.

“While this news is exciting, without insurance and Medicare coverage of this class of treatments, access will be limited to only those who can afford to pay out-of-pocket,” she noted. “The Alzheimer’s Association has submitted a formal request asking [federal officials] to remove the requirement that Medicare beneficiaries be enrolled in a clinical trial in order to receive coverage of FDA-approved Alzheimer’s treatments.”

Details from the Alzheimer’s drug clinical trial

The recent clinical trial was conducted at 235 sites in North America, Asia, and Europe between March 2019 and March 2021. The study involved nearly 1,800 adults ages 50 to 90. All the participants had some form of early dementia or Alzheimer’s disease. Half of the participants were given lecanemab and the other half were given a placebo.

Researchers reported there wasn’t a significant difference between lecanemab and the placebo at 12 months, but at 18 months it appeared the people taking lecanemab had some clearance of amyloid and less cognitive decline.

However, researchers said participants taking lecanemab had a higher percentage of adverse events than people taking the placebo at both 12 months and 18 months.

Nonetheless, officials at Biogen and Eisai, the developers of lecanemab, said the latest clinical trial provided hope for the Alzheimer’s community.

“Today’s announcement gives patients and their families hope that lecanemab, if approved, can potentially slow the progression of Alzheimer’s disease and provide a clinically meaningful impact on cognition and function,” said Michel Vounatsos, the chief executive officer at Biogen, in a statement. “Importantly, the study shows that removal of aggregated amyloid beta in the brain is associated with a slowing of disease in patients at the early stage of the disease.”

Lecanemab clinical trial provides some hope

Lecanemab is used to treat early Alzheimer’s disease. In earlier clinical trials, it was shown to lower levels of beta-amyloid plaque, a biomarker of the disease found in the brain.

“Lecanemab… is a monoclonal antibody infusion therapy that targets components of beta-amyloid, which build up… as part of the plaques and tangles that are characteristic of Alzheimer’s disease. And these new therapies effectively clear those amyloid plaques. It’s an exciting new chapter in the treatment of Alzheimer’s disease,” said Dr. Scott A. Kaiser, a geriatrician and the director of geriatric cognitive health for the Pacific Neuroscience Institute at Providence Saint John’s Health Center in Santa Monica, California.

“We know that it clears the beta-amyloid plaque,” Kaiser told Healthline in September. “The question is whether or not that actually helps with brain function. But the idea is that these plaques are interfering with the effective communication and overall interaction between brain cells and that clearing them could have positive effects.”

The toll from Alzheimer’s disease

It’s estimated that nearly 6 million people in the United States are living with Alzheimer’s disease.

Alzheimer’s disease is a form of dementia that can progress from mild memory loss in the early stages to the potential for a person with the disease to have difficulty engaging in conversation or responding appropriately to what is around them.

There is currently no cure for Alzheimer’s disease, and treatment options are limited.

“There aren’t a lot of alternatives, particularly when it comes to drugs. There are drugs that can boost certain levels of neurotransmitters and, otherwise, potentially enhance cognition. But they don’t modify the actual underlying disease pathology or disease course,” Kaiser said.

“There are some minor symptomatic treatments. It’s akin to cough syrup for somebody who has a cold. It doesn’t actually cure or treat the underlying cold, it can just provide some symptomatic relief. And in terms of pharmacotherapy for Alzheimer’s disease… that’s all there is. That’s all that’s been approved in decades,” he added.

Some hesitation about lecanemab

Lecanemab was granted breakthrough therapy designation by the FDA in June 2021.

This status is designed to speed up the development of new drugs that will address medical needs that are currently unmet for serious or life-threatening conditions.

However, some scientists have expressed concern that the earlier phase 2 trials of lecanemab had flaws and that the actual benefit of the drug to people could be limited.

“The phase 2B lecanemab studies were fatally flawed because the high dose versus placebo analysis (that supposedly showed some clinical benefit) was profoundly compromised,” Dr. Michael Greicius, a professor of neurology and neurological sciences at Stanford University in California, told Healthline.

Greicius argued that in the phase 2B trial, people who were carriers of APOE4, a type of gene associated with an increased risk of Alzheimer’s disease, were prevented midway through the trial from receiving a high dose of the treatment.  

“This means that there were many more APOE4 carriers in the placebo group (71 percent) than in the high dose group (30 percent),” Greicius explained. “This difference in percentage of APOE4 carriers is as likely (or in my view more likely) than the drug to account for the difference in clinical outcomes.”

Concerns with new drugs for Alzheimer’s disease

A similar drug, Aduhelm, has been cleared for use.

In 2021, Aduhelm received FDA approval as the first new treatment for Alzheimer’s disease since 2003. It received approval on the basis of the drug being effective at reducing beta-amyloid plaque.

“This approval was met with a great deal of criticism by the scientific community because there are no compelling data to show that reducing amyloid plaque is associated with improved clinical outcomes,” Greicius said.

“Lecanemab also has a similar profile of dangerous side effects related to brain swelling and brain bleeding that we see with Aduhelm, though lecanemab is probably a bit friendlier than Aduhelm on this front in that ‘only’ 10 percent of patients in the high dose groups showed these side effects [in the phase 2 trial],” Greicius added.



Alzheimer's Drug Lecanemab Gets FDA Approval Despite Concerns
Source: Pinoy Lang Sakalam

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