Eisai has shown 14% greater amyloid plaque removal using injections of Leqembi (Biogen and Eisai’s lecanamab-irmb) versus biweekly IV administration according to a preliminary analysis using amyloid PET at 6 months of treatment.
A substudy evaluating the sub-cutaneous (SC) formulation included 72 patients who received Leqembi for the first time SC, and 322 patients who received an intravenous (IV) of the drug in the Clarity AD core study, followed by SC administration in this substudy. Reduction from baseline of amyloid in the brain by amyloid PET at six 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 low-tau subpopulation, which is in the earlier stages of early AD, is thought to show slow disease progression. In the low-tau subpopulation, 76% of the drug treated group showed no deterioration and 60% showed clinical improvement after 18 months of treatment in the primary endpoint, Clinical Dementia Rating, compared with 55% and 28% of the placebo group, respectively.
Importantly, in this low-tau subgroup, Leqembi treatment also showed consistent clinical response across multiple endpoints. In this population, drug treatment favored cognition and function in the earlier stage of early AD.
In the Tau PET substudy, Leqembi treatment slowed the buildup of tau proteins in the temporal lobe (early Braak region), where tau accumulation was observed in the earlier stage of early AD. 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 the intermediate and higher accumulation groups. This suggests, the researchers say, that the drug may have different effects on brain regions indexed by tau depending on the stage of the disease. The spread of tau in the brain is a hallmark of AD progression.
The company reported that weekly SC administration pharmacokinetics are 11% higher than the biweekly IV formulation. They reported 90% CI for drug exposure for SC vs. IV is within the bioequivalence limits of 80% to 125%. These data could allow Eisai to select a dose that achieves pharmacokinetics that are comparable to the IV dose.
Further, in the 18-month core study of Clarity AD, there was a statistically significant difference in global cognition and function as measured by CDR-SB between the Leqembi and placebo groups. The separation in CDR-SB between the group that continued to receive the drug and (early start group) and the group who switched from placebo to Leqembi (delayed start group) was maintained during the 6-months following the core study. This indicates that similar disease trajectory for both early and delayed start groups occurred with the drug’s administration.
The blood biomarker results (plasma Aβ42/40 ratio, ptau181, GFAP and NfL) showed improvement even after delayed initiation of treatment with Leqembi, suggesting treatment may affect clinical outcomes through improvement of AD pathology.