FDA Converts Leqembi to Traditional Approval to Treat Alzheimer’s

The U.S. Food and Drug Administration (FDA) has converted Leqembi (lecanemab-irmb), 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 converted from an accelerated approval to a traditional approval 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, which allows 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, FDA required Eisai and Biogen 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 III multicenter, randomized, double-blind, placebo-controlled, parallel-group study that enrolled 1,795 patients with Alzheimer’s disease. Treatment was initiated in patients with mild cognitive impairment or mild dementia stage of disease and confirmed presence of amyloid beta pathology. Patients were randomized in a 1:1 ratio to receive placebo or Leqembi at a dose of 10 mg/kg once every two weeks. Leqembi demonstrated a statistically significant and clinically meaningful reduction of decline from baseline to 18 months on the primary endpoint, the Clinical Dementia Rating Scale Sum of Boxes score, compared to placebo. Statistically significant differences between treatment groups were also demonstrated on all secondary endpoints, which included the Alzheimer’s Disease Assessment Scale Cognitive Subscale 14 and the Alzheimer’s Disease Cooperative Study — Activities of Daily Living Scale for Mild Cognitive Impairment.

“Today’s action is the first verification that a drug targeting the underlying disease process of Alzheimer’s disease has shown clinical benefit in this devastating disease,” said Teresa Buracchio, acting director of the Office of Neuroscience in 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.”