The U.S. Food and Drug Administration (FDA) has converted the drug Leqembi (lecanemab-irmb) from accelerated approval to traditional approval for the treatment of Alzheimer’s disease. This decision was made after a confirmatory trial showed that the drug provides clinical benefit. Leqembi is the first amyloid beta-directed antibody to receive traditional approval for Alzheimer’s disease. The drug works by reducing amyloid plaques in the brain, a key feature of the disease.
Leqembi was initially approved in January under the Accelerated Approval pathway, which allows the FDA to approve drugs for serious conditions with unmet medical needs based on their effect on surrogate endpoints. As a requirement of the accelerated approval, the FDA mandated a confirmatory trial to verify the clinical benefit of Leqembi. The trial, known as Study 301 (CLARITY AD), involved 1,795 patients with Alzheimer’s disease and confirmed the efficacy of the drug in reducing cognitive decline compared to a placebo.
Teresa Buracchio, acting director of the FDA’s Office of Neuroscience, stated that this approval is the first time a drug targeting the underlying disease process of Alzheimer’s has demonstrated clinical benefit. Alzheimer’s disease affects over 6.5 million Americans and causes memory loss, cognitive decline, and difficulty performing daily tasks. While the exact cause of Alzheimer’s is not fully understood, it is characterized by the accumulation of amyloid beta plaques and neurofibrillary tangles in the brain, leading to the loss of neurons.
The FDA convened the Peripheral and Central Nervous System Drugs Advisory Committee on June 9 to discuss the clinical benefit of Leqembi. The committee unanimously agreed that the results of Study 301 confirmed the drug’s benefit in treating Alzheimer’s disease.
The most common side effects of Leqembi included headaches, infusion-related reactions, and amyloid-related imaging abnormalities (ARIA), which is a known side effect of amyloid-targeting antibodies. ARIA can manifest as temporary brain swelling and small spots of bleeding, but usually resolves over time. However, it can also present with severe symptoms, including seizures and brain edema, which can be life-threatening. The prescribing information includes a boxed warning to alert patients and caregivers to the risks associated with ARIA.
Patients who have the ApoE ε4 allele, a genetic risk factor for Alzheimer’s, have a higher incidence of ARIA when treated with Leqembi. The prescribing information recommends testing for ApoE ε4 status before starting treatment with the drug.
The use of anticoagulant medication was associated with an increased risk of intracerebral hemorrhages in patients taking Leqembi compared to a placebo. The prescribing information advises caution when considering the use of Leqembi in patients taking anticoagulants or with other risk factors for intracerebral hemorrhage.
Leqembi is contraindicated in patients who have a serious hypersensitivity to the drug or its inactive ingredients. Adverse reactions may include swelling and allergic reactions.
The drug should be initiated in patients with mild cognitive impairment or mild dementia stage of Alzheimer’s disease, as that is the population studied in clinical trials. The safety and effectiveness of Leqembi in other stages of the disease have not been evaluated.
The approval of Leqembi was granted to Eisai Inc. The FDA is an agency within the U.S. Department of Health and Human Services responsible for ensuring the safety and security of drugs, vaccines, medical devices, and other healthcare products.
