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FDA Fully Approves Lecanemab-IRMB For Early Alzheimer Disease Treatment
The United States Food and Drug Administration (FDA) has granted full, traditional approval to lecanemab-IRMB (Leqembi™) for the treatment of mild cognitive impairment or mild dementia that characterizes the early stages of Alzheimer disease (AD). The application, submitted by drug manufacturers Eisai and Biogen, received Accelerated Approval in January as well as Fast Track, Priority Review, and Breakthrough Therapy designations.
Leqembi, a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody that targets soluble and insoluble forms of amyloid beta and is administered as a 100mg/mL intravenous injection, is the first AD treatment in 2 decades to receive full FDA approval. It works to reduce amyloid plaque formation in the brain, a defining feature of Alzheimer disease that drives cognitive decline, slowing disease progression by 27% in early AD patients, according to trial results.
"Today's action is the first verification that a drug targeting the underlying disease process of Alzheimer disease has shown clinical benefit in this devastating disease," said Teresa Buracchio, MD, acting director of the Office of Neuroscience in the FDA's Center for Drug Evaluation and Research. "This confirmatory study verified that it is a safe and effective treatment for patients with Alzheimer's disease."
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Despite accelerated approval in January, lecanemab-IRMB has not yet been widely used due to an earlier decision by the Centers for Medicare and Medicare Services (CMS) that does not provide coverage for the drug. Traditional approval, though, will prompt a change in CMS coverage for the drug, which costs $26,500 out-of-pocket. The expansion of coverage will be accompanied by a requirement that patients participate in a health agency database, known as a registry, to continue to gather data on the mechanism and efficacy of the drug.
The accelerated approval granted in January was based off Phase 2 randomized, controlled study data that shows a reduction in amyloid-beta plaques in early AD patients treated with lecanemab-IRMB versus placebo. The approval was accompanied by some controversy due to 2 deaths that occurred following the conclusion of the 18-month trial. As part of the accelerated approval, the FDA stipulated that Eisai and Biogen carry out a postmarketing trial to verify lecanemab’s clinical benefit.
The phase III CLARITY AD was a multicenter, randomized, double-blind, placebo-controlled, parallel group study that included 1795 patients with AD. Patients with mild cognitive impairment or mild dementia as well as confirmed presence of amyloid beta pathology were randomized in a 1:1 ratio to receive placebo or lecanemab-IRMB (10 mg/kg) once every 2 weeks. Patients receiving Leqembi exhibited less cognitive decline overall, as measured by change on the Clinical Dementia Rating-Sum of Boxes (CDR-SB), the Alzheimer Disease Assessment Scale Cognitive Subscale 14, and the Alzheimer Disease Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment.
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Leqembi’s label will now include a black-box warning against rare, but serious and life-threatening, events, including brain swelling and bleeding. Additional potential adverse side effects of treatment with lecanemab-IRMB include a warning for amyloid-related imaging abnormalities (ARIA), which may emerge with antibodies of this class. ARIA most commonly manifests as temporary swelling in the brain that usually resolves over time and may cause headache, confusion, dizziness, vision changes, nausea, and seizure. Patients may also experience infusion-related reactions, including flu-like symptoms, nausea, vomiting, and blood pressure changes.
Some patients may be at greater risk for adverse events, including APOE4 homozygotes, those with underlying cerebral amyloid angiopathy, and those also receiving treatment with anticoagulant agents.
Lecanemab-IRMB is indicated only for the treatment of early AD, with no safety or efficacy data on initiating treatment at earlier or later stages of the disease.
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