{"id":71213,"date":"2023-08-11T09:07:10","date_gmt":"2023-08-11T15:07:10","guid":{"rendered":"https:\/\/www.uchealth.org\/today\/?p=71213"},"modified":"2024-10-18T09:54:36","modified_gmt":"2024-10-18T15:54:36","slug":"how-well-does-leqembi-fight-alzheimers-first-fda-approved-alzheimers-drug","status":"publish","type":"post","link":"https:\/\/www.uchealth.org\/today\/how-well-does-leqembi-fight-alzheimers-first-fda-approved-alzheimers-drug\/","title":{"rendered":"How well does Leqembi work to fight Alzheimer’s? First FDA-approved Alzheimer’s drug offers both promise and challenges."},"content":{"rendered":"
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A new FDA-approved drug, Lequembi, offers hope for slowing Alzheimer’s symptoms. But it’s not a cure or easy to get yet. Photo: Getty Images.<\/figcaption><\/figure>\n

The U.S. Food and Drug Administration (FDA) recently gave its first-ever full approval<\/a> for a drug designed to slow the progression of Alzheimer\u2019s disease.<\/p>\n

The drug, lecanemab, branded as Leqembi<\/a>, targets beta-amyloid, a protein that can misshape and accumulate in unhealthy levels in the brains of people with the disease. The buildup creates a sticky plaque that interferes with neurons, the brain cells that transmit information. Leqembi counters by binding to the plaque, helping to remove it.<\/p>\n

Leqembi is not a cure for Alzheimer\u2019s disease. Nor is it approved for all patients. More on that later. But in a phase 3 clinical trial<\/a> of some 1,900 patients, the drug demonstrated success in slowing cognitive and functional decline, compared to a placebo. After dozens of failed clinical trials of other drugs<\/a>, stretching back years, the approval of Leqembi was cause for hope for the nearly 7 million people with Alzheimer\u2019s disease<\/a> and their loved ones and caregivers, said Dr. Victoria Pelak<\/a>, professor of Neurology<\/a> and Ophthalmology<\/a> at the University of Colorado School of Medicine<\/a>.<\/p>\n

\u201cAny time you see a breakthrough like this, where you actually show and have evidence for slowing of clinical and functional decline, then oftentimes the floodgates open with new discoveries,\u201d Pelak said.<\/p>\n

The approval also helps to offset deep-seated pessimism that had reigned among neurologists over decades of dashed hopes for an effective treatment, said Dr. Samantha Holden<\/a>, medical director of the University of Colorado Memory Disorders Clinic<\/a>. Holden also practices at the UCHealth Neurology Clinic \u2013 Central Park<\/a>.<\/p>\n

\u201cIt\u2019s a glimmer of hope I never thought we would have during my career,\u201d said Holden, who is also an associate professor of neurology at the University of Colorado School of Medicine<\/a> on the Anschutz Medical Campus<\/a>.<\/p>\n

Like Pelak, Holden also believes the Leqembi approval could \u201cbuild momentum\u201d and attract \u201cintelligent, creative people\u201d to the effort to penetrate the mysteries of Alzheimer\u2019s disease and other forms of dementia.

Keep up to date with the latest news on Alzheimer’s disease.<\/a><\/div>\n

Leqembi is far from a cure-all, stressed Dr. Peter Pressman<\/a>, associate professor of Neurology at CU and a colleague of Holden\u2019s in the Memory Disorders Clinic. It is but one path to treating a disease likely driven by many factors. But he added that its approval could at least help to break down a widespread belief among patients, caregivers and even some providers that there is nothing that can be done to arrest the progression of Alzheimer\u2019s disease.<\/p>\n

\u201cOne of my greatest hopes for Leqembi and medications of its kind go well beyond any purported benefit of the drug itself,\u201d Pressman said. \u201cIt goes to refocusing the conversation about dementia away from just ignoring it. If Leqembi elevates opportunities to disseminate information and strengthen access to best treatment practices, that would be awesome.\u201d<\/p>\n

Much work to be done to get ready for Leqembi treatments, access to the drug<\/strong><\/h2>\n

Despite the FDA approval, Leqembi treatments will not be available at UCHealth for at least several months. Work is underway to ensure resources are in place to administer the drug safely to patients who would benefit most from it and to address other recommendations and requirements stipulated by the FDA and the Centers for Medicare and Medicaid Services (CMS).<\/p>\n

\u201cWe are completely revolutionizing the care for people living with Alzheimer\u2019s disease, and it\u2019s going to take time,\u201d Holden said. \u201cWe appreciate people\u2019s patience as we do this right. The safety of our patients is our first priority.\u201d<\/p>\n

To learn more about what the Leqembi approval means for patients and health care providers at UCHealth and the CU School of Medicine, UCHealth Today spoke with Pelak, Holden and Pressman. Each stressed that the approval generates equal measures of hope and sober realization of the demands that the approval has already generated.<\/p>\n

Leqembi targets beta-amyloid. What is beta-amyloid and how does it relate to Alzheimer\u2019s disease and its progression?<\/strong><\/h2>\n
\"Neurologist,
Neurologist, Dr. Peter Pressman, is working on ways to help primary care physicians diagnose and manage the growing number of patients with Alzheimer\u2019s disease and other types of dementia. Photo courtesy of the University of Colorado School of Medicine.<\/figcaption><\/figure>\n

Beta-amyloid is a protein found in the brains of all people. These proteins can \u201cmisfold,\u201d as Pressman put it, meaning they become misshapen. When that happens, they can build up and create the sticky plaque that clogs and slows the network of brain cells that enable thinking and memory. Think of it as a computer network disruption.<\/p>\n

Pressman added that misfolding of another key protein, tau<\/a>, causes tangles inside neurons that also deteriorate brain function. Tau was not the target of the Leqembi trial, but it is another subject of intense research into the sources of Alzheimer\u2019s disease.<\/p>\n

\u201cWe all have both beta-amyloid and tau,\u201d Pressman said. \u201cAs long as they fold in their proper configuration, they are doing the right thing.\u201d<\/p>\n

How does Leqembi work?<\/strong><\/h2>\n

Leqembi is a monoclonal antibody: a molecule designed to attack a specific target, in this case the beta-amyloid proteins that \u201caccumulate inappropriately in the brain,\u201d Pelak said. The antibodies bind to the rogue proteins, helping to clear the plaques from the brain.<\/p>\n

Who will benefit most from Leqembi? Should I consider it for a loved one who already has severe cognitive decline due to Alzheimer’s?\u00a0<\/strong><\/h2>\n

The drug is for people with mild cognitive impairment and confirmation of unhealthy levels of beta-amyloids in the brain, as determined through a spinal tap to collect cerebrospinal fluid or by PET (positron emission tomography) scans.<\/p>\n

Leqembi is not<\/strong> recommended for people with advanced cognitive decline. Pressman also pointed out that there are cases of people \u201cwhose brains were riddled with beta-amyloid at the time of death\u201d but did not show symptoms of dementia. That increases the importance of not only confirming the presence of beta-amyloids, but also associated cognitive impairment.<\/p>\n

\u201cWe don\u2019t want to give the drug to people who may not need it,\u201d Pressman said.<\/p>\n

Does Leqembi cure Alzheimer\u2019s disease?<\/strong><\/h2>\n

No. Clinical trials showed Leqembi slowed, but did not stop, the progression of cognitive and functional decline in people with Alzheimer\u2019s disease.<\/p>\n

\"Dr.
Dr. Samantha Holden heads the University of Colorado Memory Disorders Clinic. Photo by UCHealth.<\/figcaption><\/figure>\n

\u201cEven if people receive Leqembi early in the course of their disease, their cognitive function is going to decline down the road,\u201d Holden said. \u201cThat\u2019s where a lot of us are cautious of too much focus on these interventions that are still only delaying the inevitable.\u201d<\/p>\n

All three clinicians emphasized that Leqembi and other drugs that target beta-amyloids are only one element of a broad and ongoing probe of the roots of Alzheimer\u2019s disease. Pressman noted that the large pipeline of Alzheimer\u2019s drugs in development<\/a> cover targets like tau, neuro-inflammation, neuro-transmitters, metabolism and many more.<\/p>\n

Holden called Leqembi \u201cone piece of a multi-pronged approach to modifying Alzheimer\u2019s disease,\u201d and cautioned that \u201cwe can\u2019t ignore the large population of people for whom this treatment is not going to be a possibility.\u201d<\/p>\n

How do patients receive treatment with Leqembi?<\/strong><\/h2>\n

Patients receive the drug via a 30- to 60-minute infusion every other week, Holden said. That does not include time before and after the procedure, she added.<\/p>\n

How much do the treatments cost?<\/strong><\/h2>\n

The estimated annual cost of the drug alone is $26,500.<\/p>\n

Does insurance cover the cost of Leqembi?<\/strong><\/h2>\n

Medicare (CMS) will cover 80% of the cost of the drug, with Medicare patients responsible for the remaining 20% (a little more than $5,000). However, that coverage does not include associated expenses, Holden noted, such as staff to administer the infusion and MRIs three times a year to monitor for brain bleeds and swelling, which are potential side effects of the drug.<\/p>\n

Pelak noted that Medicare coverage also requires hospitals administering Leqembi to enter data about their screening and treatment into a registry maintained by CMS<\/a>.<\/p>\n

Does Leqembi have side effects?<\/strong><\/h2>\n

Yes. The most serious issues demonstrated in the trial were amyloid-related imaging abnormalities (ARIAs)<\/a>, including swelling in parts of the brain and brain bleeding. Pressman said that most ARIAs are temporary, but a small percentage of patients will have serious problems, including hemorrhaging and seizures.<\/p>\n

Are there other factors that increase the risk of using Leqembi?<\/strong><\/h2>\n
\"Dr.
Dr. Victoria Pelak is principal investigator at CU in the trial of aducanumab, another drug that targets beta-amyloid in the brain. Photo by UCHealth.<\/figcaption><\/figure>\n

Yes. People with a gene called APOE4<\/a> are at a much greater risk of developing Alzheimer\u2019s disease and other dementias and for brain swelling after receiving Leqembi. The risk is greatest for people who carry two copies of the gene.<\/p>\n

Pelak said at this point, the FDA recommends genetic testing for APOE4 \u201cto give a proper risk assessment for patients.\u201d But that adds another thorny layer of ethical and financial complexity for patients considering Leqembi and for the providers managing their care, she noted.<\/p>\n

\u201cHow can we force genetic testing on patients?\u201d Pelak said. Genetic testing could affect an individual\u2019s insurance coverage, while extensive counseling and testing would increase capacity and cost pressures, she added.<\/p>\n

Acknowledging all of these details, Leqembi is approved. Why is it not available at UCHealth yet?<\/strong><\/h2>\n

One major reason is the time and effort needed to get the infrastructure in place to accommodate patients qualified to receive the drug. Holden and Pelak noted that while UCHealth and CU did plenty of advance preparation, putting all the pieces in place couldn\u2019t proceed prior to FDA approval.<\/p>\n

The pieces include:<\/p>\n