For Immediate Release: July 06, 2023
Today, the US Food and Drug Administration upgraded Leqembi (lecanemab-Irmb), indicated for the treatment of adult patients with Alzheimer’s disease, to traditional approval after finding that a confirmatory study confirmed clinical utility. Leqembi is the first anti-amyloid beta antibody to be converted from accelerated approval to traditional approval for the treatment of Alzheimer’s disease. The drug works by reducing amyloid plaques that form in the brain, a hallmark pathophysiological feature of the disease.
Leqembi was approved under the accelerated approval process in January. This pathway allows the FDA to approve drugs for serious conditions with 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 likely to be achieved predict a clinical benefit for patients. As a post-marketing requirement of accelerated approval, the FDA required the applicant to conduct a clinical study, often referred to as a confirmatory study, to verify the expected clinical benefit of Leqembi. The efficacy of Leqembi was evaluated using the results of Study 301 (CLARITY AD), a randomized, controlled phase 3 clinical trial.
“Today’s action is the first evidence that a drug targeting the underlying disease process of Alzheimer’s disease has demonstrated clinical utility in this devastating disease,” said Teresa Buracchio, acting director of the Office of Neuroscience at the Center for FDA Drug Evaluation and Research. “This confirmatory study confirmed that it is a safe and effective treatment for patients with Alzheimer’s disease.”
Alzheimer’s disease is an irreversible, progressive brain disorder that affects more than 6.5 million Americans. The disease slowly destroys memory and thinking skills, and eventually the ability to perform simple tasks. Although the specific causes of Alzheimer’s disease are not fully understood, it is characterized by changes in the brain – including the formation of amyloid beta plaques and neurofibrillary tangles, or tau – that lead to the loss of neurons and their connections.
Study 301 was a multicentre, 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 disease-stage dementia 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 milligrams (mg)/kilogram (kg) once every two weeks. Leqembi demonstrated a statistically significant and clinically meaningful reduction in decline from baseline to 18 months in the primary endpoint, the sum of boxes of the Clinical Dementia Rating Scale score, compared to placebo. Statistically significant differences between the treatment groups were also demonstrated for all secondary endpoints, which included the cognitive subscale 14 of the Alzheimer’s Disease Rating Scale and the mild cognitive impairment scale of the Alzheimer’s Disease Cooperative Study – Activities of Daily Living.
On June 9, the FDA convened the Peripheral and Central Nervous System Drugs Advisory Committee to discuss whether Study 301 provided evidence of Leqembi’s clinical benefit in the treatment of Alzheimer’s disease. All committee members agreed that the results of the study confirmed the clinical utility of Leqembi for the indicated use.
The most common side effects with Leqembi were headache, infusion-related reactions and amyloid-related imaging abnormalities (ARIA), an adverse reaction known to occur with the class of anti-amyloid antibodies. ARIA most commonly presents as transient swelling in areas of the brain, visible on imaging tests, that usually resolves over time and may be accompanied by small spots of bleeding in or on the surface of the brain. Although ARIA is often not accompanied by any symptoms, symptoms such as headache, confusion, dizziness, blurred vision, and nausea can occur. ARIA can also, in rare cases, lead to severe and life-threatening cerebral edema, which can be associated with seizures and other serious neurological symptoms. Intracerebral hemorrhage, which can be fatal, can occur in patients treated with this class of drugs. A warning is included in the prescribing information to make patients and caregivers aware of the potential risks associated with ARIA.
Patients treated with Leqembi who are homozygous for the ApoE ε4 allele have a higher incidence of ARIA, including symptomatic, severe, and severe ARIA, compared to heterozygotes and non-carriers. The prescribing information states that prior to starting treatment with Leqembi, testing for ApoE-ε4 status should be performed to assess the risk of developing ARIA.
Anticoagulant medication use was associated with an increased number of intracerebral bleeds in patients taking Leqembi compared to placebo. The prescribing information recommends caution when using Leqembi in patients taking anticoagulants or who have other risk factors for intracerebral hemorrhage.
Leqembi is contraindicated in patients with severe hypersensitivity to lecanemab Irmb or any of its inactive components. Side effects can include angioedema (swelling) and anaphylaxis (allergic reactions).
Treatment with Leqembi should be started in patients with mild cognitive impairment or mild dementia with Alzheimer’s disease, i.e. patients in whom the treatment has been studied in clinical trials. The label states that there are no safety or efficacy data for starting treatment at earlier or later stages of the disease than those studied.
Leqembi’s approval was granted to Eisai Inc.
related information
###
boilerplate
The FDA, an agency of the United States Department of Health and Human Services, protects public health by ensuring the safety, efficacy, and safety of human and veterinary drugs, vaccines, and other biological products intended for human use, and medical devices. The agency is also responsible for the safety of the food supply, cosmetics, dietary supplements and products that emit electronic radiation, as well as for the regulation of tobacco products in our country.