FDA OK of Alzheimer’s Drug Brings Hope, Some Safety Concerns

July  7, 2023 – Experts in the Alzheimer’s disease field are throwing around works like ”breakthrough”, ”celebrate” and ”thrilled,” a day after the FDA granted full approval to a new drug to treat early stages of the disease. 

With no cure in sight, any new approval ushers in hope, including with an agent like Leqembi that slowed progression of the disease an average of 27% in research. Concerns include reports of some rare but potentially serious side effects, like brain swelling or bleeding, which prompted the FDA to require a boxed warning on the drug’s labeling.

The price could be a consideration as well. Lecanemab is estimated to cost $26,500 per year, which drug maker Eisai justifies by saying each patient treated has a $37,600 “per patient per year value” to society.

Lecanemab is intended to slow progression in people with mild thinking and memory issues in early stage Alzheimer’s disease. It’s not a cure and does not reverse the progress for people already living with more advanced disease. 

First of Its Kind

“This is the first ever traditional approval for a diseasemodifying therapy for Alzheimer’s disease. So that is a huge win for patients and families,” said Susan Peschin, president and CEO of the non-profit Alliance for Aging Research. She added that the Alliance is “thrilled” this agent earned full FDA approval. 

“We know that it’s not a cure or even a therapy that is going to have a significant long-lasting effect. But to have a therapy that slows progression of early Alzheimer’s by 27% over 18 months — that could mean a lot to people who have mild cognitive impairment,” Peschin said.

After a year-and-a-half of taking the drug, Leqembi delayed symptoms of Alzheimer’s disease by more than 5 months compared to placebo. 

Asked if this is likely to make a different in the day-to-day lives of people, Rebecca Edelmayer, PhD, senior director of scientific engagement at the Alzheimer’s Association, said yes. An additional 5.3 months of delayed progression compared to placebo in research “will be very valuable to an individual at an early stage. It means more time with family, attending graduations and be independent … so they can continue leading meaningful lives.” 

There is now hope for people with early Alzheimer’s disease, said Michael Weiner, MD, professor of radiology and biomedical imaging, medicine, psychiatry and neurology at the University of California, San Francisco. “The big picture is this is a breakthrough.” 

If you or a loved one might be or are in the early stages, “now’s the time to get to a doctor to get assessed,” said Weiner, who is also principle investigator of the Alzheimer’s Disease Neuroimaging Initiative, the largest observational study in the world for Alzheimer’s.

“If people wait too long, the door may close.”

How Safe is Treatment?

“There are definitely adverse events or side effects associated with the treatment. That’s why it carries what is called a black box warning,” Weiner said.

The FDA boxed warning is considered the highest safety-related warning for risks of “serious and life-threatening events.” The concern with Leqembi and other drugs used to treat Alzheimer’s disease is amyloid-related imaging abnormalities (ARIA) in the brain. The ARIA side effects include microbleeds and brain swelling. 

Peschin said it’s important for the public to know about these risks and to discuss them with their doctors. The risks are “minimal for many people,” she said, but added people with two copies of a genetic mutation called APOE4 are at higher risk for these side effects. 

The boxed warning is meant to call attention to some of these side effects, Edemayer said. “We really welcome those discussions to be happening between individuals or families and clinicians so they can make enforced treatment decisions.” She added that many medications to treat other conditions carry FDA box warnings. 

Weiner warned against use of Leqembi in people on blood thinning medication because of the risk of bleeding. It’s not an official FDA warning, “but if you’re on a blood thinner, a microbleed can turn out to be a macro-bleed.” 

A lot of big bleeding in the brain that can be extremely serious, he explained. There have been a few people, just a few, taking a monoclonal antibody like Leqembi or aducanumab who experienced seizures, hospitalization or death. 

An Unmet Need

The full approval was largely expected. The FDA granted Leqembi accelerated approval in January after a first study suggested it might delay the disease’s progression. The agency grants accelerated approval when there is an unmet need and a drug shows initial promise while larger studies are done. In this case, a second study confirmed the clinical benefit and the FDA granted full approval. 

Also, last month, the FDA Advisory Group reviewing evidence for Leqembi voted unanimously to recommend approval. The FDA is not bound by advisory board decisions, but usually follows their guidance.

Lecanemab addresses the underlying cause of Alzheimer’s disease. The treatment reduced the levels of amyloid plaques in the brain, the build-up of which is long thought to me a major culprit in the memory robbing disease. 

The treatment is given as I.V. infusions twice a month. Weiner hopes a more convenient pill form will be available in the future. 

Medicare Coverage, with a Catch

Also, if you’re a Medicare patient, the plan will cover 80% of the drug costs but there are a few requirements you have to meet first. The first one is obvious – you have to be enrolled in Medicare. 

But the Centers for Medicare and Medicaid Services also requires you have a diagnosis of mild cognitive impairment or mild Alzheimer’s disease dementia, with documented evidence of beta-amyloid plaques in the brain. “That is critical, you don’t want to be giving treatment to someone who is not living with Alzheimer’s disease,” Edelmayer said. 

Your doctor also has to sign up for a CMS approved registry to enter patient data and get reimbursed for care. Your doctor will take care of this last requirement. 

A Look Ahead

Drug maker Lilly has completed a phase III study of a monoclonal antibody in development for Alzheimer’s disease. It’s called donanemab and it’s expected to come up for FDA review soon. 

Another monoclonal antibody, already FDA approved for Alzheimer’s, is  Aduhelm. The June 2021 approval was controversial. All members of the FDA Advisory Board voted against its approval.

Weiner offered an optimistic, big picture perspective. 

“I think in our lifetime, we’re going to see the ability to prevent cognitive decline and dementia by identifying people who think they’re completely normal and treat them before they develop symptoms,” he said.

Alzheimer’s disease, which affects 6.5 million Americans, typically develops over 15 years and most of that time, people have no symptoms at all. 

“It’s just like early stage prostate cancer or early stage breast cancer,” he said. 

But there is research underway using scans to identify people who have amyloid plaques but do not know they have Alzheimer’s and treating them with monoclonal antibody therapy to prevent disease. Stay tuned. 

The Alzheimer’s Association encourages people with Alzheimer’s disease and their providers to enter information in their Alzheimer’s Network for Treatment and Diagnostics (ALZ-NET) registry. Launched in 2021, it aims to collect robust information on safety and efficacy of a wide range of treatments for Alzheimer’s disease to inform education, clinical care and research. 

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