Since 6 January, the anti-amyloid drug lecanemab (marketed under the brand name Leqembi™) has been available to US-based patients with mild cognitive impairment (MCI) or mild dementia due to Alzheimer’s disease (AD). However, the national coverage determination by the Centers for Medicare and Medicaid Services (CMS) limits access to participants enrolled in approved clinical research studies. On 9 June, a US Food and Drug Administration (FDA) Advisory Committee unanimously recommended traditional approval of lecanemab, which is expected to pave the way for broader access to the drug.
Lecanemab is an antibody that targets plaques of amyloid-beta proteins, which accumulate in the brain during the development of AD. Lecanemab was authorised via the FDA accelerated approval pathway, which covers medicines for serious conditions where there is an unmet medical need, and where the drug has an effect on a surrogate endpoint that is likely to predict a clinical benefit to patients. FDA approval of lecanemab was based on the positive results of a Phase 2b, randomised and placebo-controlled clinical trial, which recruited 856 patients with MCI or mild dementia due to AD.
In January this year, Eisai and Biogen filed for traditional FDA approval based on the results of their confirmatory Phase 3 study, CLARITY-AD. This study similarly showed a substantial reduction in brain amyloid, as well as a 27% slowing in clinical decline after 18 months of lecanemab treatment. During the Advisory Committee meeting, six experts including Collette Johnson, a patient advocate, discussed the findings of CLARITY-AD - with presentations from Eisai, and overviews of clinical efficacy, safety, and statistics from FDA reviewers. The advisors unanimously agreed that CLARITY-AD verified the clinical efficacy of lecanemab, showing a clear, statistically-significant slowing of clinical decline that would represent a meaningful benefit for patients.
On safety, the Committee discussed the risk of brain bleeds and swelling (also termed ARIA), which are particularly high for individuals carrying the APOE4 risk allele. They recommended that the FDA provide clear labelling to inform patients and caregivers on the risk of ARIA, and strengthen the suggestion to undergo genetic testing for APOE4. The FDA now has four weeks to consider the recommendations from the Advisory Committee, with a final decision due by 6 July. Access information and briefing documents for the Advisory Committee meeting: