Leqembi From Eisai

The FDA has approved lecanemab-irmb intravenous (IV) injection (Leqembi) from Eisai Inc for the treatment of Alzheimer disease (AD).

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Treatment should be initiated in patients with mild cognitive impairment or who are at the mild dementia stage of disease, which was when treatment began in the clinical trials. Effectiveness or safety data are not available for initiation of treatment in earlier or later stages of the disease. Lecanemab-irmb received accelerated approval from the agency based on the reduction in amyloid β plaques, and its continued approval for this indication may depend on an additional confirmatory trial.¹

Pharmacology and Pharmacokinetics

Lecanemab-irmb is a humanized IgG1 monoclonal antibody directed against aggregated soluble and insoluble forms of amyloid β. It reduces the accumulation of amyloid β plaques in the brain, which is a defining pathophysiological feature of AD. Lecanemab-irmb reaches steady-state concentration after 6 weeks of treatment and demonstrates a terminal elimination half-life of 5 to 7 days. Although albumin levels, body weight, and sex affect lecanemab-irmb exposure, none were found to be clinically significant. Because it is degraded by proteolytic enzymes, lecanemab-irmb is not expected to undergo either metabolism by hepatic enzymes or renal elimination. The pharmacokinetics of lecanemab-irmb in patients with hepatic or renal impairment was not evaluated.¹

Dosage and Administration

The presence of amyloid β pathology should be confirmed before beginning treatment with lecanemab-irmb.The recommended dose is 10 mg/kg IV once every 2 weeks. Before administration, the medication must be diluted in 250 mL of 0.9% sodium chloride injection, USP, then given as an IV infusion over approximately 1 hour via a terminal low-protein binding 0.2-μm inline filter. A brain MRI should be obtained within 1 year before treatment begins to evaluate for preexisting amyloid-related imaging abnormalities (ARIA). Additional MRIs should be obtained before the 5th, 7th, and 14th doses. Dose interruptions may be required if radiographically observed ARIA occurs.¹

Clinical Trials

Lecanemab-irmb was evaluated for efficacy in a dose-finding, double-blind, parallel-group, placebo-controlled study (Study 1, NCT01767311) of 856 participants with AD who had confirmed presence of amyloid β pathology and mild cognitive impairment or who were at the mild dementia stage of disease. Participants were randomly assigned to receive 1 of 5 doses of lecanemab-irmb or a placebo for a 79-week double-blind, placebo-controlled period, followed by a treatment-free gap period of 9 to 59 months (mean, 24 months), followed by an open-label extension period for up to 260 weeks. The study data demonstrated that participants receiving lecanemab-irmb 10 mg/kg every 2 weeks had a statistically significant reduction in brain amyloid plaque from baseline to week 79 compared with those receiving placebo.^1,2

Contraindications, Warnings, and Precautions

There are no contraindications to treatment with lecanemab-irmb.

Because lecanemab-irmb can cause amyloid-related imaging abnormalities, such as ARIA with edema (ARIA-E) and ARIA with hemosiderin deposition, enhanced clinical vigilance for ARIA is recommended during the first 14 weeks of treatment.

The risk of ARIA, including symptomatic ARIA, was increased in apolipoprotein E ε4 homozygotes compared with heterozygotes and noncarriers. Clinical evaluation, including MRI if indicated, is warranted if symptoms of ARIA occur. If infusion-related reactions occur, the infusion rate may be reduced or the infusion may be discontinued, and therapy should be administered if appropriate. Patients who experience infusion-related reactions may be considered for premedication with antihistamines, corticosteroids, or nonsteroidal anti-inflammatory drugs before subsequent doses.

The most common adverse reactions are ARIA-E, headaches, and infusion-related reactions.¹

References

1. Leqembi. Prescribing information. Eisai Inc; 2023. Accessed February 22, 2023. https://www.leqembi.com/-/media/Files/Leqembi/Prescribing-Information.pdf?hash=3d7bf1a2-5db2-4990-8388-81086f415676

2. FDA grants accelerated approval for Alzheimer’s disease treatment. News release. FDA. January 6, 2023. Accessed February 22, 2023. https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-alzheimers-disease-treatment

About the Author

Monica Holmberg, PharmD, BCPS, is a pharmacist in Phoenix, Arizona, and a Pharmacy Times contributor.