CervoMed Inc. (NASDAQ: CRVO) has announced key findings regarding neflamapimod's potential as a treatment for dementia with Lewy bodies (DLB), presented at the Clinical Trials on Alzheimer’s Disease Conference (CTAD). The data from the AscenD-LB Phase 2a trial and insights into the RewinD-LB Phase 2b clinical study suggest that neflamapimod could address the unmet need for effective DLB therapies.
Targeting Neurodegeneration in DLB
DLB, a debilitating condition affecting over 1.4 million individuals in the U.S. and EU, currently lacks approved treatments. CervoMed's approach focuses on targeting the underlying neurodegenerative processes in DLB, particularly within the basal forebrain cholinergic system. Neflamapimod, an orally administered small molecule, inhibits p38 mitogen-activated protein kinase alpha, potentially improving synaptic function.
GFAP as a Biomarker
Data from the AscenD-LB Phase 2a trial confirm that plasma glial fibrillary acidic protein (GFAP) is a reliable measure of neurodegenerative disease activity in DLB. Notably, neflamapimod treatment led to a significant reduction in plasma GFAP levels (p=0.015 versus placebo), and these reductions correlated with improvements in clinical outcomes. This suggests that neflamapimod's clinical activity is mediated by reducing neurodegenerative activity in the basal forebrain cholinergic system.
Patient Selection for RewinD-LB
The RewinD-LB Phase 2b clinical study has successfully enrolled a DLB patient population optimized to demonstrate the treatment effect of neflamapimod. By excluding patients with biomarker evidence of tau pathology, the study focuses on individuals with neurodegeneration primarily in the basal forebrain cholinergic system. According to CervoMed, this approach increases the likelihood of observing a significant clinical effect.
John Alam, MD, Chief Executive Officer of CervoMed, stated, "For both Alzheimer’s disease and DLB, the utilization of imaging and blood testing to exclude patients with high levels of tau pathology has emerged as a powerful tool to focus clinical trials on patients who have the least amounts of fixed, irreversible neurodegeneration, thereby increasing the magnitude of the clinical effect and probability of success."
Statistical Power
The RewinD-LB trial, with 80 patients per arm, was initially designed to detect a treatment effect in a mixed population of DLB patients. By exclusively enrolling patients without tau pathology, the study now has greater than 95%, approaching 100% statistical power for meeting its primary endpoint, change in CDR-SB in neflamapimod-treated patients compared to placebo. Topline data from the RewinD-LB Phase 2b clinical trial are expected in December.
