Eisai Submits sBLA for Monthly Intravenous Maintenance Dosing of Alzheimer Therapy Lecanemab


The company also submitted a request for a fast track designation specific to a subcutaneous version of lecanemab and is expected to hear back within 60 days from March 2024.

Reisa Sperling, MD, a neurologist at Brigham and Women’s Hospital, Harvard Medical School

Reisa Sperling, MD

According to an announcement from Eisai and Biogen, the companies have officially submitted a supplemental biologics license application (sBLA) for a new monthly intravenous (IV) maintenance dosing for lecanemab-irmb (Leqembi), its FDA-approved therapy for early-stage Alzheimer disease (AD). Those who’ve already completed the biweekly IV initiation phase are now eligible to receive a monthly IV does that maintains effective drug concentration to sustain the clearance of highly toxic protofibrils.1

Lecanemab, a humanized immunoglobulin gamma 1 monoclonal antibody directed against aggregated soluble and insoluble forms of amyloid-ß, was approved in July 2023 in 100 mg/mL injections for IV use. In the newly submitted sBLA, the companies included data from Study 201 (NCT01767311), a phase 2 trial, and its open-label extension (OLE), as well as the phase 3 Clarity AD trial (NCT03887455), the study that lecanemab was traditionally approved on, and its OLE.

The companies also planned to submit a BLA for a weekly maintenance therapy dose of 360 mg using a subcutaneous (SC) administration; however, the FDA brushed back, claiming it needed a fast track designation specific for the SC formulation to proceed with the review. Following the guidance, Eisai submitted a request for fast track designation for the SC formulation and noted it will initiate a rolling submission should the FDA grant this designation. A decision on this designation is expected to come within 60 days of the March 2024 submission.

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At the 2023 Clinical Trials on Alzheimer’s Disease (CTAD) Conference, data from the OLE of Clarity AD showed that a novel SC form of lecanemab resulted in greater amyloid plaque removal than biweekly IV administration. After 6 months of treatment, a subgroup of patients demonstrated a 14% increased amyloid plaque removal with the SC method than IV administration, the administration for which it was FDA-approved under.2

Presented by Reisa Sperling, MD, a neurologist at Brigham and Women’s Hospital, Harvard Medical School, the data comprised of 72 patients with early AD who received lecanemab for the first time in a subcutaneous way and 322 patients who received IV lecanemab in the Clarity AD core study followed by SC administration in the substudy. All told, investigators observed reductions of –40.3 (±2.27) centiloids at 6 months for newly treated paitents on SC lecanemab vs reductions of –35.4 (±1.14) centiloids for those on IV administration. In addition, the weekly SC pharmacokinetic area under the curve were 11% higher than the biweekly IV formulation.

In the Clarity AD core study, 12.6%, 17.3%, and 8.9% of patients reported ARIA-edema, ARIA-H (cerebral microhemorrhage because of ARIA, cerebral hemorrhage, and brain surface hemosiderin deposition) and ARIA-H alone, respectively, with intravenous lecanemab. Among the subgroup of 72 patients on subcutaneous lecanemab in the new analysis, investigators observed incidence rates of 16.7%, 22.2%, and 8.3%, respectively; however, Eisai noted that no exact comparison was made because of the sample size of individuals.

1. Eisai completes submission of Leqembi (lecanemab-irmb) supplemental biologics license application for IV maintenance dosing for the treatment of early Alzheimer disease to the US FDA. News release. Eisai. April 1, 2024. Accessed April 1, 2024. https://investors.biogen.com/news-releases/news-release-details/eisai-completes-submission-leqembir-lecanemab-irmb-supplemental
2. Irizarry M, Li D, Dhadda S, Hersch S, Reyderman L, Kramer L. Preliminary update on lecanemab safety in Clarity AD open-label extension, including subcutaneous formulation. Presented at: CTAD conference; October 24-27, 2023; Presentation 4.
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