The full approval follows an accelerated approval from January 2023 and was based on a confirmatory trial, which found lecanemab slowed disease progression compared with placebo.
FDA converted its accelerated approval of lecanemab (Leqembi) to a traditional, full approval after a confirmatory trial verified the therapy’s clinical benefit.1 As part of the full approval, CMS has revisited its restricted coverage of lecanemab and will now offer broader coverage of the therapy.2
Lecanemab is an amyloid beta-directed antibody that reduces amyloid plaques that form in the brain. Lecanemab’s accelerated approval followed a controversial accelerated approval of aducanumab (Aduhelm) in 2021. Lecanemab is now the first amyloid beta-directed antibody with full approval.
“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, acting director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research.1 “This confirmatory study verified that it is a safe and effective treatment for patients with Alzheimer’s disease.”
After aducanumab was approved, CMS announced it would restrict Medicare coverage for all approved monoclonal antibodies directed against amyloid for the treatment of Alzheimer disease to patients participating in qualifying clinical trials.3
When lecanemab was approved under the accelerated pathway, CMS said it could consider its coverage based on a review of available information and provide broader coverage.4
“CMS today affirms our commitment to help people with Alzheimer’s disease have timely access to innovative treatments that may lead to improved care and better outcomes,” CMS Administrator Chiquita Brooks-LaSure said in a statement.2 “With FDA’s decision, CMS will cover this medication broadly while continuing to gather data that will help us understand how the drug works. This is welcome news for the millions of people in this country and their families who are affected by this debilitating disease.”
FDA reviewed additional information on lecanemab from Clarity AD, a global, confirmatory phase 3 placebo-controlled, double-blind, parallel-group, randomized trial. The confirmatory trial was a requirement of the accelerated approval to verify the clinical benefit of lecanemab.
Clarity AD evaluated 1795 patients with Alzheimer disease who had mild cognitive impairment or mild dementia and a confirmed presence of amyloid beta pathology. They were randomized 1:1 to receive either a placebo or the treatment (10 mg/kg) once every 2 weeks.
The trial found lecanemab reduced cognitive and functional decline by 27% at 18 months compared with placebo.5 The drug also slowed disease progression by 24%, decline of activities of daily living by 37%, and decline of cognitive function by 26%.
The most common side effects of lecanemab were headache, infusion-related reactions, and amyloid-related imaging abnormalities (ARIA). The therapy will have a boxed warning to alert patients and caregivers to the potential risks associated with ARIA, which can infrequently present with serious and life-threatening brain edema that can be associated with seizures and other severe neurological symptoms.1
1. FDA converts novel Alzheimer’s disease treatment to traditional approval. News release. FDA. July 6, 2023. https://www.fda.gov/news-events/press-announcements/fda-converts-novel-alzheimers-disease-treatment-traditional-approval
2. Statement: broader Medicare coverage of Leqembi available following FDA traditional approval. News release. CMS. July 6, 2023. https://www.cms.gov/newsroom/press-releases/statement-broader-medicare-coverage-leqembi-available-following-fda-traditional-approval
3. CMS finalizes Medicare coverage policy for monoclonal antibodies directed against amyloid for the treatment of Alzheimer’s disease. News release. CMS. April 7, 2022. https://www.cms.gov/newsroom/press-releases/cms-finalizes-medicare-coverage-policy-monoclonal-antibodies-directed-against-amyloid-treatment
4. CMS statement on FDA accelerated approval of lecanemab. News release. CMS. January 6, 2023. https://www.cms.gov/newsroom/press-releases/cms-statement-fda-accelerated-approval-lecanemab
5. van Dyck CH, Swanson CJ, Aisen P, et al. Lecanemab in early Alzheimer disease. N Engl J Med. 2023;388(1):9-21. doi:10.1056/NEJMoa2212948