Lecanemab (Leqembi) became the first Alzheimer's treatment targeted at the disease process to win full FDA approval, the today.
"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, MD, acting director of the Office of Neuroscience in the 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."
Full FDA approval expands the anti-amyloid agent's , giving more Alzheimer's patients access to the drug.
Reaching this milestone in Alzheimer's disease treatment has been "a long journey," said Babak Tousi, MD, of the Cleveland Clinic in Ohio, an investigator in the lecanemab clinical trials. "We can affect the disease trajectory -- it's a small benefit, but it's still a benefit. We can slow it down."
"This was a big step for us, and it's not just because of the effect of the disease treatment," Tousi noted. "We learned more about the disease and learned how to diagnose it more accurately, and how to look at the process of the disease progression and biomarkers."
In January, lecanemab was approved under the to treat Alzheimer's disease. As part of the accelerated approval, drugmakers Eisai and Biogen were required to conduct a postmarketing trial verifying lecanemab's clinical benefit.
The confirmatory study, the phase III trial, showed lecanemab led to less decline on cognitive and functional measures in early Alzheimer's disease, 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 edema or effusions (ARIA-E), which occurred in 13% of people who received lecanemab. ARIA with hemosiderin deposition (ARIA-H), which includes cerebral hemorrhage 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 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 hemorrhage.
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 unanimously agreed that lecanemab showed clinical benefit in early Alzheimer's disease 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 Merit Cudkowicz, MD, of Harvard Medical School and Massachusetts General Hospital in Boston. "I was also impressed that the effect was seen relatively early -- in 6 months -- and then it seemed to get bigger with time."