FDA Panel Backs Traditional Approval of Lecanemab for Alzheimer Disease

The Food and Drug Administration’s (FDA) Peripheral and Central Nervous System Drugs Advisory Committee (PCNS) voted unanimously (6 “yes” to 0 “no”) that lecanemab-irmb (Leqembi^®) shows clinical benefit as a treatment for Alzheimer disease (AD).

Lecanemab is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble and insoluble forms of amyloid beta. In January 2023, the FDA granted accelerated approval to lecanemab for the treatment of AD based on data from a phase 2b trial (ClinicalTrials.gov Identifier: NCT01767311). In March 2023, lecanemab received Priority Review for its supplemental Biologics License Application seeking to convert its accelerated approval status to a traditional full approval.

The panel reviewed efficacy and safety data from the confirmatory phase 3 Clarity AD trial (ClinicalTrials.gov Identifier: NCT03887455), which included 1795 patients with early AD. Patients were randomly assigned 1:1 to receive either lecanemab 10mg/kg via intravenous infusion once every 2 weeks or placebo. The primary endpoint was the change from baseline to 18 months in Clinical Dementia Rating-Sum of Boxes (CDR-SB) score.

Results showed a statistically significant treatment difference in the CDR-SB score change (-0.45; P =.00005), indicating a reduction in clinical decline of 27% with lecanemab over 18 months compared with placebo. Findings also showed statistically significant improvements in all key secondary endpoints compared with placebo (P <.001), including changes in amyloid levels in the brain (as measured by amyloid positron emission tomography), the AD Assessment Scale-Cognitive Subscale 14 (-1.44 [95% CI, -2.27, -0.61]), the AD Composite Score (-0.050 [95% CI, -0.074, -0.027), and the AD Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (2.0 [95% CI, 1.2-2.8]).

The most common adverse events reported with lecanemab were infusion reactions (26.4% vs 7.4% with placebo), amyloid related imaging abnormalities-hemosiderin deposition (ARIA-H; combined cerebral microhemorrhages, cerebral macrohemorrhages, and superficial siderosis: 17.3% vs 9.0% with placebo), ARIA-E (edema/effusion: 12.6% vs 1.7% with placebo), headache (11.1% vs 8.1% with placebo), and fall (10.4% vs 9.6% with placebo).

The panel members also discussed the use of lecanemab in specific subgroups, including apolipoprotein E (ApoE) ε4 homozygote patients, patients requiring concomitant anticoagulants, and those with cerebral amyloid angiopathy.

A regulatory decision is expected on July 6, 2023. Although not bound to the committee’s recommendations, the FDA does take them into consideration when making decisions on approval.

This article originally appeared on MPR