Cognition Therapeutics Presents Promising Zervimesine Data at AAIC 2025, Highlighting Potential in Dementia with Lewy Bodies and Alzheimer’s Disease
Cognition Therapeutics unveiled encouraging Phase 2 data for its oral drug, zervimesine, in both Dementia with Lewy Bodies (DLB) and Alzheimer’s Disease (AD) at the Alzheimer’s Association International Conference (AAIC) 2025. The SHIMMER study in DLB met its primary safety and tolerability endpoint, with zervimesine demonstrating a significant impact on neuropsychiatric symptoms. Notably, patients treated with zervimesine showed an 86% improvement compared to placebo on the Neuropsychiatric Inventory (NPI-12), specifically targeting challenging symptoms like hallucinations, delusions, and anxiety. This result addresses a critical unmet need in DLB, where existing treatments for these behavioral disturbances are often poorly tolerated. The data suggests zervimesine may offer a safer and more effective approach to managing these debilitating symptoms, potentially reshaping the DLB treatment landscape. The question remains whether these positive signals will translate into larger, confirmatory trials and ultimately impact patient care.
Beyond DLB, Cognition also presented findings from the SHINE study in Alzheimer’s disease. While the study met its primary safety endpoint, a key takeaway emerged from a subgroup analysis. Patients with lower plasma p-tau217 levels, a biomarker indicating less advanced AD pathology, showed a more robust response to zervimesine, experiencing significant slowing of cognitive decline. This finding is strategically crucial as it suggests a potential path for patient stratification using a readily accessible blood test. The ability to identify patients most likely to benefit from zervimesine could significantly improve clinical trial design and potentially guide treatment decisions in real-world clinical practice. This personalized medicine approach aligns with broader industry trends towards targeted therapies and precision diagnostics. The critical next step will be validating these findings in larger, prospective studies incorporating p-tau217 assessment.
Further analyses of cerebrospinal fluid (CSF) and plasma biomarkers from the SHINE study provided mechanistic insights into zervimesine’s action. In the lower p-tau217 subgroup, significant reductions in plasma glial fibrillary acidic protein (GFAP), a marker of neuroinflammation, were observed. Trends towards normalization of neurofilament light (NFL), a marker of neurodegeneration, and amyloid beta species were also noted. These findings suggest zervimesine may exert its therapeutic effects by modulating multiple pathways implicated in AD pathogenesis, including neuroinflammation, synaptic health, and neurodegeneration. This multi-pronged approach distinguishes zervimesine from other AD therapies that primarily target single pathways. The challenge remains to fully elucidate these mechanisms and understand their relative contributions to clinical outcomes.
These data presentations from Cognition Therapeutics underscore the evolving landscape of neurodegenerative disease research and drug development. The company’s focus on sigma-2 receptor modulation represents a novel therapeutic strategy, and the early clinical signals for zervimesine are generating considerable interest. The commercial implications are substantial, particularly in DLB, where effective treatment options are limited. For Medical Affairs teams, the emergence of p-tau217 as a potential predictive biomarker raises important considerations for HCP engagement and education. Moving forward, it will be crucial to monitor the progress of zervimesine in larger, later-stage clinical trials. The potential for a safe and effective oral therapy that addresses multiple aspects of both DLB and AD holds significant promise for patients and could reshape the treatment paradigm for these devastating diseases. The question remains whether these early positive signals will translate into clinically meaningful benefits in larger populations and ultimately change the trajectory of these devastating diseases.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
