- The US Food and Drug Administration (FDA) has granted traditional approval to lecanemab for the treatment of early Alzheimer’s disease
- Approval was based on positive results from the CLARITY-AD clinical trial, which showed a 27% reduction in clinical decline for participants receiving lecanemab
- The prescribing information for lecanemab includes a warning for brain micro-bleeds and swelling and a recommendation that patients should undergo genetic testing prior to initiating treatment, due to the higher risk of brain micro-bleeds and swelling in people with two copies of the ApoE e4 allele
- The main US payer, CMS, has expanded its coverage of lecanemab to all patients with early Alzheimer’s disease and confirmed presence of amyloid plaques in the brain, widening access to the new therapy.
Luxembourg, 7 July 2023 – Yesterday, the US Food and Drug Administration (FDA) granted traditional approval to the anti-amyloid drug, lecanemab, for the treatment of early Alzheimer's disease. This approval comes after the unanimous endorsement of its clinical efficacy by an FDA Advisory Committee last month, and represents an important milestone for the Alzheimer’s community.
Lecanemab, which is marketed by Eisai and Biogen under the Leqembi® brand name, is an antibody that targets plaques of amyloid-beta proteins that accumulate in the brain during the development of Alzheimer’s disease. The FDA had previously approved lecanemab via its Accelerated Approval pathway based on the positive results of a Phase 2b, randomised and placebo-controlled clinical trial, which recruited 856 participants with mild cognitive impairment or mild dementia due to Alzheimer’s disease.
Traditional approval was based on the results of CLARITY-AD, a Phase 3, confirmatory trial which enrolled 1,795 participants who received either lecanemab (10mg/kg) or a placebo biweekly via intravenous infusion. This study met all its primary and secondary endpoints, demonstrating a 27% reduction in clinical decline after 18 months of lecanemab treatment on the global cognitive and functional scale, CDR-SB. Analysis of Quality-of-Life measures using the EQ-5D-5L and QOL-AD scales showed an average 50% reduction in decline over the 18 months of the CLARITY-AD trial.
The most common adverse events experienced by trial participants receiving lecanemab included amyloid-related imaging abnormalities, also known as ARIA. ARIA most commonly present as temporary swelling in the brain, and may be accompanied by small brain bleeds. While most cases of ARIA are mild or asymptomatic, severe ARIA can cause seizures and other life-threatening symptoms, with a reported incidence of 0.7% in CLARITY-AD. Participants carrying two copies of the ApoE e4 allele had a much higher incidence of ARIA compared to people with only one ApoE e4 copy, or non-carriers. Participants taking blood-thinning, anti-coagulant medication also experienced a larger number of brain bleeds when being treated with lecanemab.
Taking these safety concerns into account, the FDA has included a black box warning of ARIA in the prescribing information for lecanemab. This warning explains that lecanemab can cause ARIA, and states that genetic testing for ApoE e4 should be performed prior to initiation of treatment. The prescribing information explains that lecanemab treatment should be initiated in patients with mild cognitive impairment or mild dementia due to Alzheimer’s disease and confirmed presence of amyloid beta pathology in the brain. Patient monitoring should include regular MRI brain scans, with three scans during the first 14 weeks of treatment, and caution should be exercised when considering the use of lecanemab in patients on anticoagulant therapy.
In a statement released following the FDA announcement, the US Centers for Medicare and Medicaid Services (CMS) provided further details on health insurance coverage for lecanemab. To be eligible for lecanemab treatment, patients must have a confirmed diagnosis of mild cognitive impairment or mild dementia due to Alzheimer’s disease, documented evidence of amyloid beta pathology in the brain, and a prescribing physician who is participating in a registry that collects real-world evidence on patient outcomes. The CMS also stated that this coverage would be extended to similar anti-amyloid drugs that are granted traditional approval by the FDA.
Alzheimer Europe welcomes the traditional approval of lecanemab by the FDA, and the expansion of access to disease-modifying treatments for early Alzheimer’s disease in the United States. This will give hope to patients and their families, who have long been waiting for therapies that can slow or delay the cognitive and functional decline caused by Alzheimer’s disease.
European patients cannot yet access this new treatment, as lecanemab is currently undergoing a full evaluation by the European Medicines Agency, following the submission of an application for marketing authorisation approval in January 2023. Decisions by European regulators are not expected before the end of the year, but Alzheimer Europe hopes for a similarly positive outcome at European level.
Read the full FDA announcement, here: https://www.fda.gov/news-events/press-announcements/fda-converts-novel-alzheimers-disease-treatment-traditional-approval
Find the prescribing information, here: https://www.leqembi.com/-/media/Files/Leqembi/Prescribing-Information.pdf
