Data Show Three Years of Continuous Treatment with Leqembi Reduces Cognitive Decline in Patients with Early Alzheimer Disease

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Data from the Phase III global Clarity AD study of Leqembi (lecanemab-irmb) demonstrated effectiveness with three years of continuous treatment in patients with early Alzheimer disease (AD), according to Biogen and Eisai. The study, which was conducted as a joint venture, found that three years of continuous treatment with lecanemab reduced cognitive decline by -0.95 on the Clinical Dementia Rating-Sum of Boxes (CDR-SB) compared to expected declines in untreated groups. These results were presented at the Alzheimer’s Association International Conference 2024.

Leqembi is classified as an anti-amyloid beta (Aβ) protofibril antibody. According to both companies, it is the only dual-acting drug that is currently available to support neuronal function by clearing the highly toxic protofibrils that continue to cause neuronal injury and death even after plaques have been cleared from the brain.¹

“Protofibrils are thought to be the most toxic Aβ species that contribute to brain damage in AD and play a major role in the cognitive decline of this progressive and devastating disease,” reports Eisai, in a press release. “Protofibrils can cause neuronal damage in the brain, which can subsequently adversely affect cognitive function through multiple mechanisms. The mechanism by which this occurs has been reported not only by increasing the formation of insoluble Aβ plaques, but also by directly damaging signaling between neurons and other cells. It is believed that reducing protofibrils may reduce neuronal damage and cognitive impairment, potentially preventing the progression of AD.”

The global, placebo-controlled, double-blind, parallel-group, randomized Clarity AD study included 1,795 patients with early AD, of whom 898 were randomly assigned to the lecanemab 10 mg/kg bi-weekly IV treatment cohort and 897 were randomly assigned to the placebo cohort. Upon completion of the study, 95% of the study’s participants agreed to continue in the open-label extension portion. The primary endpoint of the study was the mean change from baseline according to the CDR-SB.

Results found that after three years of continuous treatment, over 50% of patients continued to show improvements in cognitive function. Additionally, a change from 0.5 to 1 on the CDR score domains of memory, community affairs and home/hobbies was the difference between slight impairment and loss of independence. As part of an additional tau PET sub study that was optional, results found that 59% of patients demonstrated improvements or no decline, while 51% showed improvement from baseline on the CDR-SB.

At the time results were presented, no new safety findings were reported after three years of treatment. According to the data, most amyloid-related imaging abnormalities occurred in the first six months of treatment, with rates decreasing as the study progressed. Common adverse events included infusion-related reactions, headache, superficial siderosis of central nervous system, rash, and nausea/vomiting.

Patients were excluded from the trial if neuroimaging displayed an increased risk for intracerebral hemorrhage. Baseline use of antithrombotic medications such as aspirin were only allowed if patients were on stable doses. Patients with factors that indicate an increased risk for intracerebral hemorrhage and patients who need to be on anticoagulant therapy should be supervised with caution.¹

According to the Centers for Disease Control and Prevention, an estimated 6.7 million Americans were living with AD last year. While it is less common, it can develop in younger people. Beyond the age of 65 years, the number of people living with the disease doubles every five years. By 2060, AD is expected to affect 14 million people in the United States.²

Eisai and Biogen are co-commercializing lecanemab, with Eisai leading its global development and regulatory processes.¹

References

1. New Clinical Data Demonstrates Three Years of Continuous Treatment with Dual-Acting LEQEMBI® (lecanemab-irmb) Continues to Significantly Benefit Early Alzheimer’s Disease Patients Presented at The Alzheimer’s Association International Conference (AAIC) 2024. Biogen. July 30, 2024. Accessed July 31, 2024. https://investors.biogen.com/news-releases/news-release-details/new-clinical-data-demonstrates-three-years-continuous-treatment

2. About Alzheimer’s Disease. CDC. Accessed July 31, 2024. https://www.cdc.gov/aging/alzheimers-disease-dementia/about-alzheimers.html#:~:text=Who%20has%20Alzheimer's%20Disease?,the%20risk%20increases%20with%20age.