The first treatment targeting Alzheimer’s disease has been given full FDA approval, the agency announced last week, giving the green light to the anti-amyloid lecanemab (Leqembi).
“This is the first verification that a drug targeting the underlying disease process of the disease has shown clinical benefit,” said Dr Teresa Buracchio, acting director of the Office of Neuroscience in the FDA’s Centre for Drug Evaluation and Research. “This confirmatory study verified that it is a safe and effective treatment for patients with Alzheimer’s.”
In January, lecanemab was approved under the accelerated approval pathway to treat the disease. MedPage Today reports that as part of the accelerated approval, drugmakers Eisai and Biogen were required to conduct a postmarketing trial verifying its clinical benefit.
The confirmatory study, the phase III CLARITY AD trial, showed lecanemab led to less declines on cognitive and functional measures in early Alzheimer's, but was associated with adverse events.
The primary efficacy endpoint was change on the Clinical Dementia Rating-Sum of Boxes (CDR-SB), a scale that ranges from 0-18, with higher scores indicating worse impairment. From a baseline score of about 3.2 on the CDR-SB, mean worsening at 18 months was 1.21 with lecanemab and 1.66 with placebo, a difference of 0.45 points.
All key secondary endpoints were met.
Adverse events included amyloid-related imaging abnormalities (ARIA) with oedema or effusions (ARIA-E), which occurred in 13% of people who received lecanemab. ARIA with hemosiderin deposition (ARIA-H), which includes cerebral haemorrhage and superficial siderosis, occurred in 17%.
Three subgroups appeared to have a higher risk of adverse events: APOE4 homozygotes, people with underlying cerebral amyloid angiopathy, and people who require concomitant treatment with anticoagulant agents.
A boxed warning is included in the lecanemab prescribing information to alert patients and caregivers to the potential risks associated with ARIA, the FDA said.
The prescribing information states that testing for APOE4 status should be performed before starting treatment to inform patients of ARIA risk, and recommends caution for patients taking anticoagulants or those who have other risk factors for intracerebral haemorrhage.
Several reports indicated that three people died during the lecanemab open-label extension study, though it was unclear what role the drug may have played.
Recent research also suggested that anti-amyloid therapies for Alzheimer’s disease, including lecanemab, may accelerate brain atrophy.
Last month, an FDA advisory committee that lecanemab showed clinical benefit in early Alzheimer’s in its confirmatory trial. In a 6-0 vote, the agency’s Peripheral and Central Nervous System Drugs Advisory Committee fully backed the evidence supporting the anti-amyloid monoclonal antibody.
The CLARITY AD findings were "robust on the primary and all the key secondary" outcomes, said FDA advisory committee member Dr Merit Cudkowicz of Harvard Medical School and Massachusetts General Hospital. “I was also impressed that the effect was seen relatively early – in six months – and then it seemed to get bigger with time.”
MedPage Today article – Alzheimer's Drug Wins Full FDA Approval (Open access)
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