Study of semorinemab in a larger mITT population confirmed statistically significant reduction in rate of cognitive decline in patients with Alzheimer disease, compared with placebo, but failed to achieve other end points.
Full topline data from the phase 2 LAURIET study (NCT03828747) of semorinemab, an investigational antitau antibody, presented by AC Immune and Genentech at the 14th Clinical Trials on Alzheimer’s Disease Conference (CTAD), November 9-12, confirmed previously announced success in meeting 1 of the 2 co-primary end points, showing a statistically significant reduction in rate of cognitive decline when compared with placebo in patients with mild-to-moderate Alzheimer disease (AD).
Data announced in August 2021 demonstrated the statistically significant reduction (43.6%; P <.0025) in rate of cognitive decline at week 49 for those taking semorinemab vs placebo, as measured by the Alzheimer’s Disease Assessment Scale, Cognitive Subscale, 11-item Version (ADAS-Cog11). At CTAD, data were presented from a larger modified intent to treat (mITT) population (n = 241), including patients who had received 1 or more dose of study drug and had 1 post-baseline ADAS-Cog11 assessment.
According to data, patients in the larger population taking semorinemab had a 42.2% reduction in rate of cognitive decline, when compared to placebo (P = .0008). Prespecified subgroups were consistent with treatment effect, regardless of disease severity, baseline Tau load, and APOE carrier status. Positive safety data was also confirmed in the CTAD presentation, and serious adverse events were consistent between both treatment arms.
Notably, there was no significant treatment effect on the second co-primary end point, change from baseline in activities of daily living, as measured by the Alzheimer’s Disease Cooperative Study-Activities of Daily Living scale. Additionally, secondary efficacy end points—change in Mini-Mental State Examination and Clinical Dementia Rating-Sum of Boxes scores—were not achieved. A total of 204 patients with mild-to-moderate AD who had missed 1 or more dose of study drug were included in the prespecified mITT population. The open label extension of the trial is ongoing.
“We are pleased that the data presented at CTAD confirm LAURIET’s remarkable findings, which provide the first evidence of therapeutic impact on cognition for an anti-Tau monoclonal antibody in mild-to-moderate AD, by showing a statistically significant slowing of the rate of cognitive decline,” Andrea Pfeifer, PhD, CEO, AC Immune, said in a statement. “We thus remain encouraged by the LAURIET data, while still being cautious about what it may mean for patients, given the lack of effect on functional endpoints. AD is a slow progressing chronic disease, therefore, we look forward to learning about semorinemab’s longer-term effects through the ongoing open-label extension, which is being conducted by our partners at Genentech.”
Also presented at CTAD were biomarker analyses; when assessed by positron emission tomography, no treatment effect was identified on global or regional Tau distribution. Similar to other studies, treatment with semorinemab also showed pronounced increase in plasma Tau levels when analyzed, which may indicate peripheral tau binding. The ratio of the level of semorinemab in the cerebrospinal fluid to that in plasma fell in the expected range (mean 0.29%), as did levels of semorinemab in plasma.
“The finding of significant slowing of cognitive loss assessed by ADAS-Cog 11 in the LAURIET study is an important result and one that should be further analyzed. It is the first example of a monoclonal anti-Tau antibody slowing cognitive decline in mild-to-moderate AD, adding to an emerging dataset that provides a strong scientific rationale for Tau as a valid target in Alzheimer’s disease,” Johannes Streffer, MD, chief medical officer, AC Immune, said in a statement.
For more coverage of CTAD 2021, click here.