Semorinemab May Slow Cognitive Decline in Mild-to-Moderate Alzheimer Disease

In the placebo-controlled, phase 2 Lauriet study (NCT03828747), semorinemab (AC Immune SA, Lausanne, Switzerland), slowed cognitive decline as measured with the Alzheimer Disease Assessment Scale, Cognitive Subscale, 11-item version (ADAS-Cog11). Semorinemab is a monoclonal antibody to tau. 

Participants (n=272) with mild-to-moderate Alzheimer disease (AD) were treated with semorinemab or placebo for 49 weeks. Those treated with semorinemab had a 43.6% slower rate of decline on the ADAS-Cog11 compared with those treated with placebo (P<.0025). On other measures, however, including the Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating-Sum of Boxes (CDR-SB), no statistically significant differences between semorinemab and placebo treatments were observed. There was also no effect on the rate of functional decline from baseline as measured by the Alzheimer Disease Cooperative Study-Activities of Daily Living (ADCS-ADL). The planned open-label extension of the Lauriet study will be continued by Genentech, a Roche company, (South San Francisco, CA). 

Rachelle Doody, MD, PhD, global head of Neurodegeneration at Roche, noted that this is "another important step in our understanding of the role of tau and the potential for semorinemab to make a difference in the progress of this complex and difficult-to-treat disease. We are grateful to all of the patients, families, caregivers and clinicians involved in the Lauriet study, and we remain committed to following the science and exploring multiple approaches and molecules that are designed to address key pathways of AD, including tau and beta-amyloid, as well as comprehensive approaches to AD care.”

In an earlier trial of semorinemab, the phase 2 Tauriel study (NCT03289143) in people with prodromal-to-mild AD, target engagement and dose-dependent effects on cerebrospinal fluid (CSF) tau levels were seen. However, in that study, no changes in neurodegeneration, as measured by neurofilament light (NfL) levels, were observed. In the Lauriet study data reported today, changes in total tau and tau spread in the brain were not observed. Indices of regional tau levels in the brain are still pending, as are other biomarker studies (including CSF tau). Further analyses of the trial data will be presented at the Clinical Trials on AD (CTAD) conference in November.

Professor Andrea Pfeifer, chief executive officer of AC Immune SA said, “(this) is the first time we have seen a therapeutic effect by a monoclonal antitau therapy. Nevertheless, despite these interesting results, we are still cautious about what this may mean for patients as there was not an impact on the rate of functional decline or other efficacy endpoints. With that said, AD is a slow-moving chronic disease, and this small trial was relatively short, 49 weeks; so, the data from the open-label extension may be important in elucidating the potential of semorinemab in this patient population.”