July 6, 2023
The U.S. Food and Drug Administration converted Leqembi (lecanemab), indicated to treat adult patients with Alzheimer’s Disease, to traditional approval following a determination that a confirmatory trial verified clinical benefit. Leqembi is the first amyloid beta-directed antibody to be fully approved for the treatment of Alzheimer’s disease. The drug works by reducing amyloid plaques that form in the brain, a defining pathophysiological feature of the disease.
Leqembi was approved in January under the Accelerated Approval pathway. This pathway allows the FDA to approve drugs for serious conditions where there is an unmet medical need, based on clinical data demonstrating the drug’s effect on a surrogate endpoint—in the case of Leqembi, reducing amyloid plaques in the brain—that is reasonably likely to predict a clinical benefit to patients. As a postmarketing requirement of the accelerated approval, the FDA required the applicant to conduct a clinical trial, often referred to as a confirmatory study, to verify the anticipated clinical benefit of Leqembi. Efficacy of Leqembi was evaluated using the results of Study 301 (CLARITY AD), a Phase 3 randomized, controlled clinical trial.
In the phase 3 “Clarity AD” trial1, 1795 patients with Mild Cognitive Impairment (MCI) or mild dementia due to AD were randomized to receive 10 mg/kg biweekly intravenous infusions of lecanemab or placebo for 18 months. Primary and secondary outcomes—as well as multiple “downstream” biomarkers of AD pathophysiology (CSF and plasma pTau, plasma GFAP, CSF neurogranin, and tau PET)—all favored lecanemab, demonstrating clear-cut clinical benefit and possible modification of disease pathophysiology.
Later the same day, the Center for Medicare Services announced that they will cover this class of medications if they receive full FDA approval.
“Reflecting on our experiences as clinician-scientists in the AD field for two decades, I and my colleagues marvel at the tremendous progress in developing in vivo biomarkers of AD pathology and biologically-potent therapeutics. Progress has not been linear, and treatment trials have been fraught with setbacks. Yet with Clarity AD many of us believe the tide is turning, and a new era of AD care is surfacing—an era in which an accurate clinical diagnosis will be made with high confidence at an early stage with the support of biomarkers, opening the door to molecular-specific therapies. Though much work remains, lecanemab’s success represents a major milestone for the field, and a moment of great hope for patients and families living with this devastating disease.” – Brad Dickerson, MD