The Food and Drug Administration (FDA) has granted accelerated approval to Leqembi™ (lecanemab-irmb) for the treatment of Alzheimer disease (AD).

Leqembi is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble and insoluble forms of amyloid beta. It reduces amyloid beta plaques in the brain, which is a defining pathophysiological feature of Alzheimer disease.

The accelerated approval was based on a reduction in amyloid beta plaques observed in patients treated with Leqembi. In a phase 2b study (ClinicalTrials.gov Identifier: NCT01767311), 856 patients with early AD and confirmed amyloid pathology (using positron emission tomography [PET] imaging) were randomly assigned to receive 1 of 5 doses of lecanemab-irmb (161 patients received the recommended dosing regimen of 10mg/kg every 2 weeks) or placebo (n=247).

In a subgroup of patients enrolled in the amyloid PET substudy, findings showed that treatment with lecanemab 10mg/kg every 2 weeks resulted in a statistically significant reduction in brain amyloid plaque from baseline to week 79 compared with placebo (difference from placebo, -0.310 [P <.001]). This effect correlated with improvements in cognitive decline based on the Clinical Dementia Rating-Sum-of-Boxes (CDR-SB) and the Alzheimer Disease Assessment Scale-Cognitive Subscale scores at week 79.

Under the accelerated approval pathway, a confirmatory trial is required to confirm the clinical benefit of lecanemab. According to the FDA, data from the phase 3 Clarity AD trial (ClinicalTrials.gov Identifier: NCT03887455), which was recently reported, will serve as the confirmatory trial. The study showed a statistically significant treatment difference in the CDR-SB score change, indicating a reduction in clinical decline with lecanemab compared with placebo.

“The unquestionably positive data from the clinical studies of Leqembi indicate that thorough removal of beta amyloid from the brain leads to clinical benefit,” said Maria C. Carrillo, PhD, Alzheimer’s Association chief science officer in a statement. “This treatment can change the course of Alzheimer’s in a meaningful way for people in the early stages of the disease, allowing more time to participate in daily life and live independently.”

Treatment with Leqembi should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials. There are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied.

As for safety, the most common adverse reactions reported with treatment included infusion-related reactions, headache, and amyloid related imaging abnormalities-edema.

Leqembi is supplied as a preservative-free solution in single-dose vials of 500mg/5mL and 200mg/2mL. Treatment is administered by intravenous infusion once every 2 weeks. The Company say it will be available on or before January 23, 2023.

References

  1. FDA grants accelerated approval for Alzheimer’s disease treatment. News release. Accessed January 6, 2023. https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-alzheimers-disease-treatment.
  2. Leqembi. Package insert. Eisai; 2022. Accessed January 6, 2023. https://www.leqembi.com/-/media/Files/Leqembi/Prescribing-Information.pdf.