Subcutaneous Leqembi Clears More Amyloid than IV Formulation

Weekly subcutaneous administration of Leqembi (lecanemab-irmb) removed 14% more amyloid plaque in patients with Alzheimer’s disease than the biweekly intravenous formulation, according to new data released at the annual Clinical Trials on Alzheimer’s Disease (CTAD) conference in Boston. Additionally, 60% of the patients with early stage Alzheimer’s disease and who have low levels of the protein tau achieved cognitive improvement when treated with Leqembi.

Developed by Eisai and Biogen, Leqembi has been on the market since January 2023 as an intravenous formulation with an accelerated approval. It has a list price of $26,500 a year. The IV formulation of Leqembi received full approval in July 2023 based on phase 3 data from Eisai’s global Clarity AD clinical trial.

Related: CMS Expands Leqembi Coverage After FDA’s Full Approval

The new data come from the open-label extension of the Clarity AD study. In a substudy, 72 patients received Leqembi for the first time as the subcutaneous formulation, and 322 patients received the IV formulation followed by subcutaneous administration. Amyloid in the brain was measured by PET scan at six months.

Systemic injection/infusion reactions are uncommon and mild with subcutaneous administration, and 8.1% of patients in the subcutaneous first administration had injection site reactions. Most were mild and moderate in severity consisting of redness, irritation, or swelling. Rates of amyloid-related imaging abnormalities (ARIA) were similar in both arms. But because of the small number of patients receiving subcutaneous Leqembi researchers said comparisons couldn’t be made.

In addition, researchers conducted a post hoc analysis assessing patients with high vs. low levels of the tau protein in the brain, which indicates an earlier stage of the disease. In the patients with low levels of tau, 76% showed no deterioration of cognition after treatment with Leqembi, and 60% showed clinical improvement after 18 months of treatment in the primary endpoint.

In the Tau PET substudy, Leqembi suppressed the accumulation of tau in the medial temporal brain region in low-tau subpopulations, and in a broader range of brain regions in patients with higher levels. Researchers said this suggests that Leqemb treatment may have different effects on brain regions depending on the stage of the disease.

Eisai aims to submit a biologics license application for Leqembi SC to the FDA by March 31, 2024.