Eisai and Biogen Start Rolling Biologics License Application Submission to FDA for Subcutaneous Version of Alzheimer Disease Drug Leqembi

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Eisai and Biogen Inc. have initiated a rolling FDA submission for a subcutaneous (SC) version of Leqembi (lecanemab-irmb) to treat Alzheimer disease (AD) in patients with mild cognitive impairment (MCI) or the mild dementia stage of AD.¹ The Biologics License Application (BLA) for Leqembi, which was granted fast track designation by the FDA based on findings from the Clarity AD (Study 301) trial, seeks approval for weekly SC autoinjector maintenance dosing.

Leqembi is a humanized IgG1 monoclonal antibody directed against aggregated soluble and insoluble forms of amyloid β (Aβ). The medication decreases the accumulation of Aβ plaque in the brain, which is a defining pathophysiological feature of AD.

“As part of the [SC] autoinjector 360 mg weekly maintenance regimen under review, patients who have completed the biweekly [intravenous (IV)] initiation phase would receive weekly doses that maintain effective drug concentrations to sustain the clearance of highly toxic protofibrils which can continue to cause neuronal injury even after the (Aβ) plaque has been cleared from the brain,” Biogen stated in a press release.¹

In the release, Eisai and Biogen noted that the Leqembi SC autoinjector can reduce the amount of time patients with AD spend in the clinic receiving IV infusion while also lowering the burden on caregivers and healthcare providers. The SC version, administered as two consecutive injections, could allow patients to receive Leqembi at home instead of visiting an infusion center twice per month.

“This SC autoinjector is easier for patients and their care partners to use, and may reduce the need for hospital visits and nursing care compared to (IV) administration,” Biogen stated in the press release. “In addition to potentially maintaining the clinical and biomarker benefits, subcutaneous maintenance dosing may be more convenient for patients and their care partners to continue the treatment.”¹

In an open label extension of the Clarity AD trial, 72 patients with AD, who had not received prior treatment with Leqembi, were administered the SC version of the drug to compare the results with 322 patients who were administered IV Leqembi in the Clarity AD core study followed by SC administration in the substudy.²

Following six months of therapy, the SC formulation of Leqembi removed 14% more amyloid plaque than the currently approved IV formulation. Additionally, blood concentration levels with the SC form of Leqembi were 11% higher than the IV version. The decrease from baseline in amyloid plaque in the brain by amyloid PET at six months among patients newly treated with SC Leqembi per centiloid reduction was -40.3 ± 2.27 in SC administration compared to -35.4 ± 1.14 with IV administration.²

Rates of infusion- and injection-related adverse effects (AEs) were lower among patients administered SC Leqembi, whereas rates of serious AEs were higher. Incidence of amyloid-related imaging abnormalities (ARIA)-E was 16.7% in the SC Leqembi patient group compared with 12.6% in the Leqembi IV patient group. ARIA-H was reported by 22.2% of patients in the SC Leqembi patient group compared with 17.3% in the IV Leqembi patient group. An analysis of a small subgroup of patients with early AD found that in patients with low levels of tau, 60% experienced improvements in cognitive function compared with 28% of patients given placebo.²

Earlier this year, Biogen announced it would discontinue the development and commercialization of its AD treatment Aduhelm (aducanumab-avwa) to focus instead on Leqembi. Aduhelm was granted accelerated approval by the FDA in June 2021 as a first-of-its kind therapy for AD.^3,4

References

1. Eisai Initiates Rolling Biologics License Application to US FDA for LEQEMBI® (lecanemab-irmb) for Subcutaneous Maintenance Dosing for the Treatment of Early Alzheimer’s Disease Under the Fast Track Status. News release. Biogen. May 14, 2024. Accessed May 15, 2024. https://investors.biogen.com/news-releases/news-release-details/eisai-initiates-rolling-biologics-license-application-us-fda

2. 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. Accessed May 15, 2024. https://investors.biogen.com/news-releases/news-release-details/eisai-presents-new-leqembir-lecanemab-irmb-investigational

3. Biogen to Realign Resources for Alzheimer's Disease Franchise. Biogen. News release. January 31, 2024. Accessed May 15, 2024. https://investors.biogen.com/news-releases/news-release-details/biogen-realign-resources-alzheimers-disease-franchise

4. FDA Grants Accelerated Approval for Alzheimer’s Drug. News release. FDA. June 7, 2021. Accessed May 15, 2024. https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-alzheimers-drug