Semorinemab Phase 2 Trial Shows Significant Reduction in Cognitive Decline in Mild-to-Moderate Alzheimer’s Disease

On November 10, 2021, AC Immune and Genentech, a subsidiary of Roche, announced the latest results of a Phase 2 clinical trial for semorinemab, an anti-tau monoclonal antibody. The trial aimed to evaluate the safety and efficacy of semorinemab in treating patients with mild to moderate Alzheimer's disease (AD). The trial demonstrated a significant impact of semorinemab in slowing cognitive decline in a broader patient population.

In the brains of AD patients, the deposition of β-amyloid and neurofibrillary tangles caused by the misfolding of tau protein are two typical pathological hallmarks, and they are also two important targets for the development of AD therapies. Pathological tau proteins can spread between neurons, thereby propagating to more brain regions and leading to clinical disease progression. Semorinemab is a monoclonal antibody targeting the N-terminal region of tau protein. It is designed to delay the propagation of tau proteins between neurons by binding to them.

Previously released data showed that, using the ADAS-Cog11 scale to assess cognitive levels in AD patients, after 49 weeks of treatment, the decline in cognitive abilities in the semorinemab group (N=204) was reduced by 43.6% (p<0.0025) compared to the placebo group, achieving one of the trial's primary endpoints. However, semorinemab did not reach the other primary endpoint of this trial, as it had no effect on the decline in patients' daily functioning assessed by ADCS-ADL.

The full results released this time show that, among 241 patients, the rate of cognitive decline in the semorinemab group was reduced by 42.2% (p=0.0008) compared to placebo based on the ADAS-Cog11 assessment. Moreover, regardless of disease severity, tau burden, or APOE genotype, the benefits of semorinemab on ADAS-Cog11 were consistent with the treatment effect observed in the overall cohort across all pre-specified subgroups. Analysis of ADAS-Cog11 scores indicates that the therapeutic effect of semorinemab was primarily driven by scores evaluating memory components, a core feature of Alzheimer's disease (AD). However, no significant treatment effects were observed for the other co-primary or secondary endpoints of the trial.

In addition, tau positron emission tomography (PET) analysis showed no effect of treatment on overall or regional tau distribution in the brain. Plasma tau analysis showed a significant increase in plasma tau levels in patients after semorinemab treatment, indicating peripheral tau binding, consistent with previous studies.

In terms of safety, semorinemab was generally well-tolerated, with a balanced incidence of adverse events and serious adverse events between the two treatment groups, and no unexpected safety signals were observed.

References:

[1] AC Immune Announces Late-Breaker Presentation by Genentech at CTAD on Phase 2 Lauriet Study of Semorinemab in Mild-to-Moderate Alzheimer’s Disease. Retrieved November 10, 2021, from https://ir.acimmune.com/news-releases/news-release-details/ac-immune-announces-late-breaker-presentation-genentech-ctad

(Original text has been abridged)

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