Subcutaneous Lecanemab Found Equally Effective as IV Version in Alzheimer Disease Treatment

An injectable version of lecanemab-irmb (Leqembi; Eisai Co., Ltd) 100 mg/mL showed equal efficacy to the intravenous (IV) version of the drug in removing toxic brain plaques in patients with Alzheimer disease (AD), according to research presented at the 16th annual Clinical Trials on Alzheimer’s Disease (CTAD) conference held in Boston, Massachusetts. A weekly dose of the drug administered as 2 consecutive injections could allow patients to receive lecanemab at home instead of visiting an infusion center twice per month.¹

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According to data presented at the CTAD conference, after 6 months of treatment, the subcutaneous (SC) form of lecanemab removed 14% more amyloid plaque than the currently approved IV formulation. Further, blood concentration levels of SC lecanemab were 11% higher than the IV version.¹

In an open-label extension (OLE) of the Clarity AD study, investigators administered the SC formulation of lecanemab to 72 patients who were receiving the drug for the first time to compare them with 322 patients administered IV lecanemab in the Clarity AD core study followed by SC administration in the substudy.

“Reduction from baseline of amyloid in the brain by amyloid PET at 6 months in the newly treated SC patients by centiloid reduction was -40.3 ± 2.27 in SC administration compared to -35.4 ± 1.14 in IV administration,” the investigators wrote.

In terms of safety, the rates of infusion- and injection-related adverse effects (AEs) were lower for the SC version of the drug; however, rates of serious AEs were higher. Incidence of amyloid-related imaging abnormalities (ARIA)-E was 16.7% in the SC cohort compared with 12.6% in the IV cohort. ARIA-H was reported in 22.2% in the SC cohort compared with 17.3% in the IV cohort.

An analysis of a small subgroup of patients with early AD showed that among individuals with low levels of tau, 60% showed improvements in cognitive function vs 28% of patients administered a placebo.

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.²

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 ARIA. Additional MRIs should be obtained before the 5th, 7th, and 14th doses. Dose interruptions may be required if radiographically observed ARIA occurs.²

Eisai stated that it will submit a Biologics License Application (BLA) to the FDA by March 31, 2024 for the SC version of lecanemab.

References

1. Eisai Presents New LEQEMBI® (lecanemab-irmb) Investigational Subcutaneous Formulation Interim Study Results and Clinical Improvement Data in Earlier Stages of Early Alzheimer’s Disease From Additional Analyses of Clarity AD at The Clinical Trials on Alzheimer’s Disease (CTAD). Eisai. News release. October 25, 2023. https://investors.biogen.com/news-releases/news-release-details/eisai-presents-new-leqembir-lecanemab-irmb-investigational

2. Holmberg, M. Leqembi From Eisai. Pharmacy Times. Published June 20, 2023. Accessed October 26, 2023. https://www.pharmacytimes.com/view/leqembi-from-eisai