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August 2023 LEQEMBI: WHAT PHYSICIANS NEED TO KNOW ABOUT THE NEW ALZHEIMER’S DRUGFeaturing: Ian M. Grant, MD
The Food and Drug Administration (FDA) recently awarded full approval to Leqembi® (lecanemab), a drug that delays progression of Alzheimer’s disease at its earliest stages. Northwestern Medicine has started to offer the drug to interested and eligible patients through Mesulam Center for Cognitive Neurology and Alzheimer’s Disease. While Leqembi is far from a cure for Alzheimer’s, its launch is a landmark moment, says Ian M. Grant, MD, a behavioral neurologist and director of Clinical Trials at the center. “Leqembi is the first anti-amyloid drug shown to clearly produce a clinical change — it’s a small change but a real change,” Dr. Grant says. “I think this could be comparable to the early days of HIV therapy. There will be further advances, and initial therapies will be built on to improve outcomes.” Here, Dr. Grant discusses the benefits and risks of Leqembi, how Northwestern Medicine is providing the drug, and what referring physicians should know. What are the benefits and risks of Leqembi, and the demand so far? “In clinical trials, Leqembi resulted in a 28% slower decline compared to placebo,” Dr. Grant says. “An easier way to think about it is that this equates to four to five additional months of retained function. Patients and families won’t see a day-to-day difference, but the drug is doing something.” Dr. Grant says about one in five patients on Leqembi experience amyloid-related imaging abnormalities (ARIA), generally asymptomatic swelling or bleeding in the brain. But sometimes ARIA is accompanied by transient symptoms, such as headache, confusion and visual disturbance. Rarely, ARIA presents as life-threatening brain edema and bleeding. “We’ve started the conversation about the drug with our existing patients at the Mesulam Center and are also getting some calls from new people,” Dr. Grant says. “I think there is a lot of interest and curiosity, but so far not overwhelming demand. When we go over everything — the potential benefits, side effects, time commitment, monitoring — people are more lukewarm. A handful really want to start the drug, and a lot more want to talk about it.” The approval of Leqembi follows the approval of a similar drug, aducanumab, in June 2021. But aducanumab has not been widely used because, while it does reduce amyloid plaques in the brain, its clinical benefit was less clearly proven in a pair of incomplete clinical trials. How will Northwestern Medicine make Leqembi available to patients? Initially, Leqembi will only be prescribed at Northwestern Medicine through physicians at the Mesulam Center, and Northwestern Memorial Hospital will be the only location where patients can receive the twice-monthly infusions of the drug. Behavioral neurologists will evaluate patients’ stage of illness through cognitive and functional tests, as Leqembi is not effective when Alzheimer’s has already progressed beyond the early stages. Patients will undergo an MRI of the brain and either a lumbar puncture or an amyloid PET scan to confirm presence of amyloid plagues, the drug’s target. Additionally, patients will be tested for the ApoE4 gene, which is associated with increased frequency and severity of ARIA. Northwestern Medicine has decided not to give Leqembi to patients with two copies of the ApoE4 gene because the risk of ARIA is significantly greater, Dr. Grant says. Northwestern Medicine also will exclude patients on blood thinners because of increased risk of brain bleeding, he says. To monitor for ARIA, patients will receive three MRI scans during the first six months of treatment when ARIA is most common, and an additional scan at 12 months as ARIA can occur later, though that is less common. Clinical trials for Leqembi provided 18 months of treatment. Currently, there is no specified stopping point, Dr. Grant says, although that might change with more data. “Our plan is to continue patients on the drug as long as it’s tolerated for at least 18 months, the length of the study, and potentially for as long as people are in mild stages of the disease,” he says. What should referring physicians know? Physicians who see patients who may be interested in Leqembi should know the exclusion criteria in the Appropriate Use Recommendations, Dr. Grant says. “The big exclusion criteria are being on a blood thinner and being too far progressed in the disease,” he says. “Being too far progressed includes patients who are obviously very impaired, such as being dependent on others to get dressed and for daily needs.” For patients who are interested in the drug and not clearly beyond the early stages of Alzheimer’s, Dr. Grant recommends placing a Neurobehavioral Referral to the Mesulam Center because stage of illness can be hard to evaluate. Additionally, referring physicians should be aware of a new direct-to-consumer test that can measure amyloid beta proteins in plasma. “You may see patients who have taken the test and are concerned about their status,” Dr. Grant says. “The Leqembi clinical trials didn’t use blood proteins as a standalone biomarker to exclude patients. So regardless of results on these tests, it’s OK to refer patients for evaluation. With blood tests, there is a risk of false positives, and we don’t know if they are useful for very early stages of the disease.” Will Northwestern Medicine expand capacity to provide Leqembi? While infusions initially will be provided only at the Mesulam Center, physician leaders hope to expand infusions to other Northwestern Medicine Neurology locations by the beginning of 2024. By that time, another Alzheimer’s drug — donanemab — is expected to have received FDA approval and will likely increase demand for infusions. As with Leqembi, donanemab is an amyloid plague-targeting therapy that has slowed progression of Alzheimer’s in clinical trials. Once other Northwestern Medicine neurologists are adequately familiar with the Appropriate Use Recommendations, prescribing will be expanded to other Northwestern Medicine Neurology locations as well, Dr. Grant says. Current MRI capacity at Northwestern Medicine is expected to be sufficient for qualifying and monitoring patients, he says. The Centers for Medicare & Medicaid Services (CMS) is considering covering amyloid PET scans in addition to cerebrospinal fluid testing for proof of amyloid positivity. “We have less capacity for PET, so will be selective in its use,” Dr. Grant says. As more drugs come on the market, “it seems likely our capacity will have to grow, but it’s hard to predict exactly how right now,” he says. For example, while infusions are the current form of delivery, drugmakers are working on subcutaneous forms that patients could inject themselves at home. What are the financial considerations around Leqembi? Leqembi is priced at $26,500 per year, and monitoring and other care will add significantly to its costs. CMS will cover the drug if patients are enrolled in a registry that is tracking results. Private coverage is still being settled. Additionally, the drug’s manufacturer, Eisai, has established a patient assistance program to supply the drug at no cost to uninsured and financially burdened patients who meet the program eligibility criteria. Northwestern Medicine will offer financial counseling to help patients prepare. “There are concerns that less advantaged patients will have a harder time accessing the drug, but so far, we are seeing a decent mix of people who qualify to receive it and have coverage,” Dr. Grant says. “We will continuously evaluate how the drug is being provided to ensure that it’s being done so equitably.” Resources Leqembi (lecanemab)
Donanemab
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Ian M. Grant, MD, Assistant Professor of Neurology (Behavioral Neurology) and Neurology (Hospital Neurology)
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