The headline on the UCHealth Today blog posting summed it up: “First FDA-approved drug offers both promise and challenges.” This was in reference to Leqembi (generic name: lecanemab), a drug designed to slow the progression of Alzheimer’s disease.
The blog included comments and perspectives from three physicians associated with UCHealth and the University of Colorado School of Medicine. These three are:
- Dr. Victoria Pelak, professor of Neurology and Ophthalmology at the University of Colorado School of Medicine
- Dr. Samantha Holden, medical director of the University of Colorado Memory Disorders Clinic
- Dr. Peter Pressman, associate professor of Neurology at CU and a colleague of Holden’s in the Memory Disorders Clinic
The three discussed a number of the “promises and challenges” Leqembi presents. We will offer several of their key points here. (We will not include much in the way of the pharmacology of Leqembi — the details of how it works. If interested, you can read more about those details in our AgeWise article at https://agewisecolorado.org/blog/alzheimers-drugs-are-works-in-progress/.)
Leqembi® is not a cure for Coloradans with Alzheimer’s
All three doctors emphasized that Leqembi is not a cure for Alzheimer’s. Nor is it approved for all patients. But clinical trials have demonstrated the drug’s success in slowing cognitive and functional decline, compared to a placebo. Dr. Pelak observed: “Any 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.” Dr. Holden echoed this, saying a drug like Leqembi can offset pessimism about finding an effective treatment and could build momentum in trying to unravel the mysteries of Alzheimer’s and other forms of dementia.
Dr. Pelak added that this is cause for hope for the nearly 7 million people in the U.S. with Alzheimer’s and their loved ones and caregivers. In 2020, the Alzheimer’s Association estimated that there were 76,000 people aged 65 or older living with Alzheimer’s in Colorado, a number projected to increase to 92,000 by 2025.
Dr. Pressman stressed that Leqembi is far from a cure-all, but it may still reassure patients, caregivers and even some providers that the quest to find a way to arrest the progression of Alzheimer’s is not futile. “One of my greatest hopes for Leqembi and medications of its kind go well beyond any purported benefit of the drug itself,” Dr. Pressman said. “It goes to refocusing the conversation about dementia away from just ignoring it.”
Leqembi® is Limited to Coloradans with mild impairment
The physicians pointed out that Leqembi is for people with mild cognitive impairment and confirmed unhealthy levels of beta-amyloids in the brain, proteins long thought to be a key causative factor for Alzheimer’s. These beta-amyloids are typically determined through a spinal tap to collect cerebrospinal fluid or by PET (positron emission tomography) scans. Leqembi is not recommended for people with advanced cognitive decline. Dr. Pressman added that there are cases of people “whose brains were riddled with beta-amyloid at the time of death” but did not show symptoms of dementia. He said this increases the importance of not only confirming the presence of beta-amyloids, but also associated cognitive impairment. As he put it: “We don’t want to give the drug to people who may not need it.”
Dr. Holden said it’s also important to maintain perspective. Clinical trials of Leqembi never showed it to be able to stop the progression of cognitive decline but rather just slow it down. “Even if people receive Leqembi early in the course of their disease, their cognitive function is going to decline down the road,” she said. On a particularly sober note, she reminded that at this point a drug like Leqembi is “still only delaying the inevitable.”
She added that this drug right now is one piece of a broader effort to look into modifying Alzheimer’s disease, and she said “we can’t ignore the large population of people for whom this treatment is not going to be a possibility” (such as those with severe/advanced cognitive decline).
Coloradans could experience Leqembi’s side effects
There is also the matter of side effects. UCHealth’s blog noted that one of the most serious issues that arose in drug trials were what are called amyloid-related imaging abnormalities, or ARIAs. These included swelling in parts of the brain and brain bleeding. Dr. Pressman said that most ARIAs are temporary, but a small percentage of patients will have serious problems, including hemorrhaging and seizures. (Significant swelling and bleeding in the brain were notable side effects of a similar preceding drug called Aduhelm® [generic name: aducanumab], which did not gain full FDA approval as Leqembi did. There were also questions about Aduhelm’s effectiveness.)
The blog further observed that people with a gene called APOE4 are at a much greater risk of developing Alzheimer’s disease and other dementias and also at greater risk for brain swelling after receiving Leqembi. Dr. Pelak said at this point, the FDA recommends genetic testing for APOE4 in order to get a proper risk assessment. She acknowledged this adds a layer of ethical and financial complexity for patients considering Leqembi and for the providers managing their care. For instance, she said, if genetic testing is done, this could affect an individual’s insurance coverage. Counseling and testing would also add to costs.
Costs that Coloradans are likely to face for Leqembi®
Patients approved for Leqembi receive the drug via a 30- to 60-minute intravenous infusion every other week, according to Dr. Holden. This does not include time before and after the procedure. The estimated annual cost of the drug alone is $26,500. Medicare has said it will cover 80% of the cost of the drug, with Medicare patients responsible for the remaining 20% (so a little more than $5,000). However, Dr. Holden noted, that coverage does not include associated expenses, such as staff to administer the infusion and MRIs three times a year to monitor for brain bleeds and swelling, the potential side effects of the drug.
Medicare coverage reportedly also requires hospitals administering Leqembi to enter data about their screening and treatment into a registry maintained by the Centers for Medicare and Medicaid Services (CMS).
Treatments with Leqembi® not immediately available in Colorado
UCHealth said Leqembi treatments will not be available at its facilities for at least several months. The health network said, “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 CMS.” Drs. Holden and Pelak noted it requires time and effort to get the infrastructure in place to accommodate patients qualified to receive the drug. This includes getting the drug on formulary, establishing billing codes, ensuring adequate availability of infusion equipment and staff to administer treatments, developing a protocol for determining those most likely to benefit from receiving the drug (and also determining who is ineligible), and crafting reliable safety monitoring protocols prior to, during, and after infusions.
All three doctors added that the overall healthcare workforce of today is ill-equipped to fully address the needs of millions of people with Alzheimer’s. Dr. Pressman has written an article in which he argues that the main responsibility for diagnosing and managing dementia falls on primary care, which he called “the already strained backbone of the American medical system.” He advocates for developing automated systems and other measures to help providers with cognitive screenings, assessments, treatment options.
Dr. Pelak agreed that “Everybody recognizes the primary care issue. Screening to help people recognize when a cognitive issue is due to Alzheimer’s disease is very important. We are working on ways to find and create resources to help PCPs [primary care providers] and geriatricians not be overburdened with the act of figuring out whether or not someone with cognitive complaints has Alzheimer’s disease.”
Dr. Holden added that the need to bolster help for primary care providers is especially acute because of a severe nationwide shortage of behavioral neurologists, who specialize in the diagnosis and treatment of dementia. “There are not enough of us to go around,” she said. She noted further that “blockbuster drugs” are usually for very rare conditions, but in the case of Leqembi, “we are talking about 7 million people with Alzheimer’s disease. This is a turning point in many different ways, including for the health care system as a whole and how we deliver care equitably for a population that has basically been ignored.”
Coloradans should stay sensitive to signs of cognitive decline
Especially now that a drug shows some promise for those with mild cognitive impairment, meaning those who are presumably in the early stages of Alzheimer’s disease, Dr. Holden says it’s important to help people get into care and not ignore warning signs like memory loss and confusion. She stressed that the sooner a person seeks help for signs of cognitive decline, the better their outlook will be. “Proper diagnosis is critical to discovery and treatment of dementia,” Dr. Pelak added. “We need to figure out why a person has dementia or determine if cognitive impairment is due to causes other than dementia, such as depression or small strokes.”
The doctors also pointed out that ongoing studies continue to show that diet and exercise can improve brain aging and decrease cognitive decline in its mild phases. Dr. Holden said one of the strongest interventions can still be the lifestyle one follows.
Acknowledgement: Appreciation to UCHealth Today for significant content in this article.