In a key step for Alzheimer’s disease (AD) treatment, the FDA has fully approved Biogen’s and Eisai’s Leqembi (lecanemab), the first drug shown to reduce the rate of disease progression and to slow cognitive and functional decline in adults.
Several treatments are available that address symptoms of AD, but the search for drugs that can address the disease’s underlying causes has been long and arduous. Most current evidence suggests the main culprit is amyloid (Aβ) plaques.
“Today, the FDA approved Leqembi under the traditional approval pathway, making Leqembi the first and only approved anti-amyloid Alzheimer’s disease treatment shown to reduce the rate of disease progression and to slow cognitive impairment in the early and mild dementia stages of the disease,” said Haruo Naito, CEO at Eisai, in a press release yesterday.
In trials, Leqembi demonstrated clinically meaningful slowing of cognitive and functional decline in a patient group generalizable to U.S. Medicare beneficiaries, which included a mix of racial and ethnic groups, patients with common comorbid conditions, concomitant medications, and patients with mild cognitive impairment due to AD or mild AD.
The drug’s full approval is based on Phase III data from Eisai’s large, global Clarity AD clinical trial, the results of which were presented at the Clinical Trials on Alzheimer’s Disease (CTAD) 2022 conference and published in The New England Journal of Medicine on November 29, 2022.
In this trial, Leqembi met its primary endpoint and all key secondary endpoints with statistically significant results and confirmed the clinical benefit of the drug. The primary endpoint was the global cognitive and functional scale, Clinical Dementia Rating Sum of Boxes (CDR-SB). Treatment reduced clinical decline on CDR-SB by 27% at 18 months compared to placebo.
Additionally, the secondary endpoint of AD Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS MCI-ADL), as measured by people caring for patients with AD, noted a statistically significant benefit of 37%. This measures the ability of patients to function independently, including being able to dress, feed themselves, and participate in community activities.
Following FDA’s traditional approval of Leqembi, CMS confirmed that broader coverage of the drug is now available and released more details on the CMS-facilitated registry now available for healthcare professionals to submit required patient data to CMS. Medicare will cover this therapy for appropriate patients.
Leqembi is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble (protofibril) and insoluble forms of Aβ. The drug targets and clears the most neurotoxic form of Aβ that continuously accumulates as well as removes the existing plaques to treat this progressive, chronic disease.
In June 2023, the FDA’s Peripheral and Central Nervous System Drugs (PCNS) advisory committee voted unanimously that the data from Eisai’s Clarity AD clinical trial confirmed the clinical benefit of Leqembi. Committee members also confirmed the drug’s overall risk-benefit and on January 6, 2023, it was approved by the FDA under the accelerated approval pathway.
