Eisai and Biogen Report Positive Clinical Data for Subcutaneous Formulation of Leqembi (lecanemab) in Alzheimer’s Disease

▎WuXi

Edited by Kant Content Team

Recently, Eisai and Biogen announced the efficacy and safety data of their Alzheimer's disease (AD) antibody therapy Leqembi (lecanemab) subcutaneous formulation in the Clarity AD open-label extension (OLE) trial. Preliminary data show,The brain amyloid clearance rate of its investigational subcutaneous formulation is 14% higher than that of the approved Leqembi intravenous formulation.And exhibit a similar rate of amyloid-related imaging abnormalities (ARIA).The company plans to submit a Biologics License Application (BLA) for the Leqembi subcutaneous formulation to the U.S. FDA by March 31, 2024.

Alzheimer's disease is the most common neurodegenerative disease in the elderly, and amyloid plaque deposition is a hallmark feature of patients' brains. Targeting amyloid is one of the key directions in the development of new drugs for Alzheimer’s disease.Leqembi is a targeted amyloid antibody that binds to soluble β-amyloid aggregates and promotes their clearance.It has the potential to alter disease pathology and slow disease progression. Earlier this year, the FDA granted accelerated approval for its market release based on clinical trial results showing that Leqembi reduced amyloid levels in patients' brains, and in JulyFull ApprovalThis therapy enabled Leqembi intravenous formulation to become the first Alzheimer's disease drug to receive full FDA approval in 20 years.

The results announced this time are from a sub-study within the Clarity AD open-label extension trial, which evaluated the subcutaneous formulation of Leqembi. The sub-study included 72 patients who were newly treated with the subcutaneous formulation of Leqembi (without prior use of the intravenous formulation). Additionally, it included 322 patients from the core Clarity AD study who had previously been treated with the intravenous formulation of Leqembi but were switched to the subcutaneous formulation during the subsequent sub-study.

The results of the trials announced this time are as follows:

1) At 6 months of treatment, the preliminary analysis of amyloid positron emission tomography (PET) showed,Weekly subcutaneous administration shows a 14% higher amyloid plaque clearance rate compared to biweekly intravenous administration.The reduction in brain amyloid levels from baseline was -40.3±2.27 for the subcutaneous administration group and -35.4±1.14 for the intravenous administration group.

2）The area under the curve (AUC) of pharmacokinetic parameters for patients receiving subcutaneous administration once a week is 11% higher than that for the intravenous formulation administered once every two weeks.The 90% CI for subcutaneous and intravenous drug exposure falls within the 80%-125% bioequivalence limits.

3）When administered subcutaneously, patients rarely experience systemic injection/infusion reactions, and such reactions are mostly mild., and this phenomenon has not been observed in patients receiving subcutaneous formulations for the first time. Overall, the incidence of local injection site reactions in patients receiving subcutaneous treatment is low (8.1%). Most of the severity is mild to moderate, including redness, irritation, or swelling. No rash or other hypersensitivity reactions were reported.

Image Source: 123RF

4) In the Clarity AD core study, the incidence rates of ARIA-E (ARIA-edema), ARIA-H (ARIA-hemorrhage), and ARIA-H alone (without ARIA-E) in patients (n=898) treated with Leqembi intravenous formulation were 12.6%, 17.3%, and 8.9%, respectively.In the new treatment patients (n=72) of the Clarity AD OLE subcutaneous formulation sub-study, the rates of ARIA-E, ARIA-H, and ARIA-H only were 16.7%, 22.2%, and 8.3%, respectively.However, due to the small sample size of patients in the subcutaneous formulation sub-study, a definitive comparison could not be made.

The approved Leqembi requires patients to visit a medical clinic every two weeks for intravenous injection.If the subcutaneous formulation is approved, patients can self-administer it at home or receive subcutaneous injections through a caregiver, which is expected to significantly improve medication adherence.