Semorinemab Slows Decline in Cognition, Top-line Results Show
Treatment with the investigational anti-tau monoclonal antibody semorinemab significantly slowed decline in a measure of cognition among people with mild-to-moderate Alzheimer’s disease in the Phase 2 LAURIET clinical trial, top-line results show.
“The top line results of the Lauriet Phase 2 clinical trial of semorinemab are remarkable in that it is the first time we have seen a therapeutic effect by a monoclonal anti-Tau antibody therapy,” Andrea Pfeifer, PhD, CEO at AC Immune, said in a press release.
“We also are excited by the fact that this is the first time a monoclonal antibody has had a therapeutic impact on cognition in the mild-to-moderate AD patient population,” Pfeifer added. AC Immune is co-developing semorinemab alongside Genentech, a Roche company.
In the brains of people with Alzheimer’s, a protein called tau forms abnormal “tangles” that are thought to contribute to disease progression. By binding to the tau protein, semorinemab is designed to stop these tangles from forming and growing, thereby halting disease progression.
The LAURIET clinical trial (NCT03828747), sponsored by Genentech, enrolled 272 adults with mild-to-moderate Alzheimer’s at 43 study centers around the globe. Participants were randomly assigned to receive either semorinemab or a placebo for 49 weeks, or about one year.
The study’s primary endpoint — its main measure of efficacy — was a change in scores on two standardized assessments: the Alzheimer’s Disease Assessment Scale, Cognitive Subscale, 11-item Version (ADAS-Cog11), which measures cognition, and the Alzheimer’s Disease Cooperative Study–Activities of Daily Living (ADCS–ADL), which assesses difficulties in day-to-day tasks.
Top-line results — the trial’s initial findings — showed that semorinemab treatment significantly reduced the rate of decline in ADAS-Cog11, by 43.6% compared with the placebo.
However, the treatment did not significantly affect scores on the ADCS–ADL. Semorinemab treatment also did not significantly affect scores on two secondary measures of cognition, the Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating–Sum of Boxes (CDR-SB).
Further analyses of the trial data are ongoing, according to the researchers.
“Although we are encouraged by the positive outcome for one co-primary endpoint measuring cognitive performance, we will continue our analyses of these data and continue the open label portion of the study to better understand why semorinemab didn’t show an effect on the co-primary endpoint measuring functional decline in activities of daily living, or on the secondary endpoints,” Rachelle Doody, MD, PhD, global head of neurodegeneration at Roche, said in an email to Alzheimer’s News Today.
Participants who completed the LAURIET trial had the option of enrolling in an open-label extension study, in which all participants will get the active medication and continue to be monitored for safety and efficacy.
“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,” Pfeifer said.
“With that said, AD [Alzheimer’s disease] 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,” Pfeifer said.
More broadly, the positive results from this trial support targeting tau as a therapeutic strategy in Alzheimer’s, she added.
Doody said the researchers “remain committed to following the science” and are continuing to explore varying approaches.
“The topline Lauriet results in people living with mild-to-moderate Alzheimer’s disease are 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,” Doody said.
Top-line results from a separate Phase 2 clinical trial called TAURIEL (NCT03289143), which tested semorinemab in people with early Alzheimer’s, were released last year and showed no evidence of benefit.