New Alzheimer’s drug raises hopes – but also questions

The FDA has approved Leqembi, the first disease-modifying treatment for early-stage Alzheimer’s and its precursors, mild cognitive impairment. Medicare has announced that it will pay for the therapy. Medical centers across the country are scrambling to finalize policies and procedures for getting the drugs to patients, possibly by late summer or early fall.

It’s a tense moment when hope is high for families and other promising therapies like donanemab are on the horizon. Still, medical providers are cautious. “This is an important first step in developing treatments for complex neurodegenerative diseases, but it’s only a first step,” said Ronald Petersen, director of the Mayo Clinic’s Alzheimer’s Research Center in Rochester, Minnesota.

As we enter this new era of treatment for mild cognitive impairment and early-stage Alzheimer’s, there are many unanswered questions. Will Leqembi’s main benefit – a slight slowing of cognitive and performance decline – make a significant difference for patients and family members, or will it be difficult to detect? Will its effects speed up, slow down, or flatten out over time?

Will demand for Leqembi (the brand name for lecanemab), a monoclonal antibody that requires biweekly infusions, be robust or subdued? How many older adults in their 70s and 80s will be able and willing to drive to medical centers twice a month for IV fluids and undergo regular MRI scans and doctor visits to watch for possible side effects like brain hemorrhage or swelling?

How many people, even with Medicare coverage, can afford the medical services they need, including cognitive testing, IV fluids, doctor’s appointments, MRI scans, genetic testing, and spinal biopsy or PET scans to check for the presence of amyloid plaques? a hallmark of Alzheimer’s and a prerequisite for this therapy?

Will primary care physicians begin routinely screening older adults for mild cognitive impairment, which is not the case at present?

These questions are not surprising given that these dementia treatments are breaking new ground. Here’s some of what people should know:

Leqembi basics. Leqembi is very effective at clearing amyloid plaques (a protein that clumps between neurons) from people’s brains. But it cannot reverse cognitive decline or prevent future deterioration.

in one briefing documentAccording to Eisai, the company that makes Leqembi, clinical studies showed a 27% slower rate of decline in people taking the drug. However, looking at the raw scores on the cognitive scale used to measure outcomes (4.41 for the Leqembi group at the end of 18 months versus 4.86 for the placebo group), the improvement rate was 9%, said Lon Schneider, professor of psychiatry, neurology and gerontology at the University of Southern California’s Keck School of Medicine.

Benefits can be difficult to see. Research suggests that patients notice a “clinically meaningful” change in cognitive performance — a noticeable change in their ability to think, remember, and perform everyday tasks — when scores on an 18-point scale used to measure cognitive function Effect used by Leqembi to increase at least 1 point. However, in patients taking this drug, the change seen at 18 months was only 0.45%.

“It’s a minimal difference, and people are unlikely to see any real change in cognitive functioning,” said Alberto Espay, professor of neurology at the University of Cincinnati College of Medicine.

Petersen has a different view, as many patients have told him they would like to delay worsening. “If we can keep these patients stable for a little bit longer, that makes sense,” he told me.

Side effects are common. The medicines manufacturer reported that 17% of the patients taking Leqembi experienced swelling in the brain and 13% had bleeding in the brain. Most of these side effects occurred during the first three months of treatment and disappeared four months later without serious consequences.

Infusion-related side effects also occurred in just over one in four cases – chills, pain, nausea, vomiting, a rise or fall in blood pressure, and more.

A little-discussed side effect is a reduction in brain volume associated with Leqembi and other anti-amyloid therapies. “We don’t know what this will mean for patients in the long term, and that’s worrying,” Espay said.

Because people with the APOE4 gene variant, which increases the risk of Alzheimer’s, are also at higher risk of side effects from Leqembi, doctors at major medical centers will recommend genetic testing when evaluating potential patients.

Not all patients are suitable for this. “I select very carefully the patients I think are appropriate, focusing on people with mild cognitive symptoms who are otherwise healthy,” said Erik Musiek, associate professor of neurology at Washington University School of Medicine in St. Louis.

He has about 20 patients ready to begin treatment once Washington University offers Leqembi, perhaps early fall. Delivering this therapy “is going to be challenging, and I think we have to play it safe,” he said.

In Los Angeles, UCLA Health has established a multidisciplinary group of specialists, similar to a cancer tumor board, to conduct comprehensive screenings of patients who wish to take Leqembi, said Keith Vossel, director of the Mary S. Easton Center for Alzheimer’s Research at UCLA Care. They will disqualify people with more than four microbleeds detected on brain MRI, those taking blood thinners and people with a history of seizures.

At the Mayo Clinic in Minnesota, a new Alzheimer’s therapy clinic will carefully screen potential patients for three to four days and only treat people who live within a 100-mile radius. “We start with patients who are reasonably healthy and follow them very closely,” Petersen said.

At the Mount Sinai School of Medicine in New York City, Mary Sano, director of Alzheimer’s research, is concerned about elderly patients with mild cognitive impairment who want to take Leqembi but have no signs of amyloid plaque buildup in their brain. “We only treat people who are amyloid positive and I’m afraid this could make people feel like we’re not taking care of them,” she said. Studies show that about 40 to 60% of patients aged 58 and over with mild cognitive impairment are amyloid positive.

Patients with moderate Alzheimer’s disease or early-stage cognitive impairment due to vascular dementia or various metabolic causes are also of concern. They too would not be able to conquer Leqembi and could well be disappointed, Sano noted.

The costs could be significant. Leqembi’s cost is difficult to calculate because Medicare officials haven’t disclosed how much the government will pay for the services. But the University of Southern California estimates that a year’s care, including the $26,500 for the drugs, could total about $90,000, according to Schneider.

A separate analysis The Institute for Clinical and Economic Review study estimates that all medical services needed to administer the drug, monitor patients, and perform necessary tests, in addition to Leqembi’s direct costs, average $82,500 per year could be.

Assuming a 20% patient deductible, that would mean a minimum of $18,000 in deductible. While many older adults have supplemental insurance (a Medigap plan or employer-sponsored retirement plan) to help meet these costs, nearly one in 10 Medicare beneficiaries lack this type of protection. And it remains to be seen what policies private Medicare Advantage plans will implement for this drug.

We look forward to hearing from our readers what questions you have answered, what issues you have had with your care and what advice you need on dealing with the healthcare system. Visit kffhealthnews.org/columnists to submit your requests or tips.

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