Study also showed that 76% of individuals treated with lecanemab-irmb had no deterioration in the tau positron emission tomography (PET) subset.
A study of lecanemab-irmb (Leqembi; Eisai Co Ltd, Biogen Inc) 100 mg/mL demonstrated that the weekly subcutaneous formulation showed 14% greater amyloid plaque removal compared to the biweekly intravenous (IV) administration at 6 months of treatment for Alzheimer disease (AD), according to results in a preliminary analysis. Furthermore, the subcutaneous pharmacokinetics of the drug were higher than the intravenous administration by 11%.
The new data, along with data from a tau positron emission tomography (PET) subset, were presented as late breaking findings at the 16th annual Clinical Trials on Alzheimer’s Disease conference, held in Boston, Massachusetts from October 24 to October 27, 2023.
Investigators evaluated a subcutaneous formulation in a sub-study of the open-label Clarity AD (NCT03887455) extension study. The study included 72 individuals who received the subcutaneous drug for the first time and 322 who received the IV drug, followed by subcutaneous administration.
Additionally, the investigators found that there was a reduction in baseline amyloid in the brain at 6 months in patients who were newly treated with the subcutaneous administration by centiloid reduction of -40.3 ± 2.27 compared to -35.4 ± 1.14 for the IV administration. Investigators also found that there were lower rates of systemic injections with the subcutaneous injection. They reported that there was a low rate of local injection site reactions, including redness, irritation, or swelling, which were mostly mild and moderate. There were no other skin rashes or hypersensitivity reactions, according to the results.
Furthermore, the incidence of amyloid-related imaging abnormalities (ARIA) for the subcutaneous formulation were consistent with the rates from the IV formulation. The incidence of ARIA-E, ARIA-H, and ARIA-H without ARIA-E for the intravenous formulation was 12.6%, 17.3%, and 8.9%, respectively, and were 16.7%, 22.2% and 8.3%, respectively, with the subcutaneous formulation. However, due to the small number of individuals in the subset, investigators said that no exact comparison could be made.
In phase 2 and phase 3 clinical trial results, investigators said the maximum exposure was the strongest predictor of ARIA incidence after IV administration, but steady-state exposure was a better predictor in the subcutaneous group.
According to a statement, Eisai plans to submit the subcutaneous formulation’s Biologics License Application to the FDA by March 31, 2024.
Additionally, another subset in the Clarity AD study also included a Tau PET subset, which investigators used to identify individuals who had a low accumulation of tau in the brain, representing earlier stage of early AD. In the subpopulation, 76% of individuals who were treated with lecanemab-irmb had no deterioration and 60% had clinical improvement after 18 months compared with 55% and 28%, respectively, in the placebo group.
Furthermore, treatment with lecanemab-irmb demonstrated consistent clinical response across the endpoints, with efficacy also being consistent with the overall results of the Clarity AD study, according to the results. Lecanemab-irmb also demonstrated favored cognition and function within the earlier stage of early AD.
The drug also slowed the buildup of tau proteins in the frontal lobe, according to the results. Lecanemab-irmb also suppressed the accumulation in the medial temporal brain region with low-tau subpopulations and broader regions with intermediate and high accumulation of tau.
Although these results are promising, the investigators said these results are from the investigational use of the drugs and are not intended to demonstrate conclusive efficacy or safety.
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) conference. News release. Eisai; Biogen. October 2023. Accessed October 30, 2023. Email.