The US Food and Drug Administration (FDA) converted the approval process for Leqembi ( lecanemab-irmb), indicated for the treatment of adult patients with Alzheimer’s disease, is on traditional approval after a confirmatory study verified clinical benefit. Leqembi is the first antibody directed against amyloid-beta protein to move from an accelerated to a traditional approval process 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 in January under the accelerated approval track. 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 an alternate endpoint—in Leqembi’s case, plaque reduction amyloid in the brain—which is reasonably likely to predict clinical benefit to patients. As a post-marketing requirement for accelerated approval, the FDA required the applicant to conduct a clinical study, often referred to as a confirmatory study, to verify the anticipated clinical benefit of Leqembi. The efficacy of Leqembi was evaluated using the results of Study 301 (CLARITY AD), a Phase 3 randomized controlled clinical study.
“Now’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 Center for Evaluation and Evaluation’s Office of Neuroscience . FDA Drug Investigation. “This confirmatory study verified that it is a safe and effective treatment for patients with Alzheimer’s disease.”
Alzheimer’s disease is an irreversible and progressive brain disorder that affects more than 6.5 million people in the United States. 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 beta-amyloid plaques and neurofibrillary tangles, or tau—that result in the loss of neurons and their connections.
Study 301 was a 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 disease-stage dementia and confirmed presence of beta-amyloid pathology. Patients were randomized in a 1:1 ratio to receive either placebo or Leqembi at a dose of 10 milligrams (mg)/kilograms (kg), once every two weeks. Leqembi demonstrated both a statistically significant and a clinically significant reduction in the decline from baseline to 18 months in the primary endpoint, the Dementia Clinical Rating Scale Sum of Boxes score, compared with the placebo.
On June 9, the FDA convened the Advisory Committee for Drugs for the Central and Peripheral Nervous System to discuss whether study 301 provided evidence of clinical benefit for Leqembi for the treatment of Alzheimer’s disease. All committee members voted that the study results verified the clinical benefit of Leqembi for its indicated use.
The most common side effects of Leqembi were headache, infusion-related reactions, and amyloid-related imaging abnormalities (ARIA), a side effect known to occur with the class of antibodies that target the amyloid. ARIAs most often present as temporary swelling in areas of the brain seen on imaging studies that usually resolve over time and may be accompanied by small spots of bleeding on or on the surface of the brain. Although ARIAs are often not associated with any symptoms, symptoms can occur and include headache, confusion, dizziness, vision changes, and nausea. ARIAs can also infrequently present with severe and life-threatening cerebral edema that may be associated with seizures and other severe neurological symptoms. Intracerebral hemorrhages can occur in patients treated with this class of drugs and can be fatal. A boxed warning is included in the prescribing information to alert patients and caregivers to the potential risks associated with ARIAs.
Leqembi-treated patients who are homozygous for the ApoE ε4 allele have a higher incidence of ARIAs, including symptomatic, severe, and severe ARIAs, compared with heterozygotes and non-carriers. The prescribing information states that a test for ApoE ε4 status should be performed prior to starting treatment with Leqembi to inform the risk of developing ARIAs.
The use of anticoagulant medicines was associated with a greater number of intracerebral bleeds in patients taking Leqembi compared with placebo. The prescribing information recommends caution when considering the use of Leqembi in patients taking anticoagulants or with other risk factors for intracerebral hemorrhage.
Leqembi is contraindicated in patients with severe hypersensitivity to lecanemab-irmb or any of its inactive ingredients. Adverse reactions may include angioedema (swelling) and anaphylaxis (allergic reaction).
Leqembi should be started in patients with mild cognitive impairment or the mild dementia stage of Alzheimer’s disease, the population in which the treatment was studied in clinical trials. The labeling indicates that there are no safety or efficacy data on initiation of treatment earlier or later in the disease than those studied.
SOURCE: PRNewswire