Multi-Modal Correlation Analyses From a Phase 2, Open-Label Study of NE3107 in Patients With Cognitive Decline Due to Degenerative Dementias (P7-6.010)

Abstract

<h3>Objective:</h3> To determine correlations among changes in inflammatory markers, improvements in neuropsychological health, changes in brain metabolism and functional connectivity, and changes in patients’ daily abilities after NE3107 treatment. <h3>Background:</h3> Lowering chronic neuroinflammation may slow Alzheimer’s disease (AD) progression. An exploratory, 3-month, phase 2 trial of NE3107, an oral, anti-inflammatory molecule, enrolled 23 patients, 17 with mild cognitive impairment (MCI) to mild dementia [Mini-Mental State Examination (MMSE) scores ≥20] and 6 patients with moderate dementia (MMSE scores &lt;20). In patients with MMSE ≥20, NE3107 treatment was associated with significant improvements in cognitive performance, including the AD assessment Scale-Cognitive Subscale 12 (ADAS-Cog12), trending improvements in biomarker levels, including tumor necrosis factor-α (TNF-α), significant improvements in the Global Rating of Change (GRC), and enhanced neurophysiological health. We assessed correlations between the anti-inflammatory effects and meaningful clinical outcomes. <h3>Design/Methods:</h3> Eligible patients had a Clinical Dementia Rating score of 0.5 (MCI) or 1 (mild dementia). Clinicians, patients, and caregivers completed a GRC at study completion. Correlations between changes from baseline in cognitive function (ADAS-Cog12) and the key inflammatory biomarker (TNF-α) or patient global impression (GRC) were determined. Hypothesis-based examination of metabolic and functional brain imaging was initiated. <h3>Results:</h3> Patients had a mean age of 71.6 (SD=9.63) years and 15 (65%) were females. In patients with MMSE ≥20, reductions in TNF-α significantly correlated with improvements in ADAS-Cog12 scores (r=0.7; p=0.0077). Improvements in cognition, based on changes in ADAS-Cog12, significantly correlated with clinician-observed improvements in GRC outcomes (r=−0.52; p&lt;0.05). Neuroimaging data suggest correlations with other study outcomes. <h3>Conclusions:</h3> Correlations among improved cognitive function, reduced inflammation, and changes in the clinician-observed GRC (overall impression of patient’s abilities) were consistent with the hypothesized activities of NE3107. Preliminary examination of metabolic and functional brain imaging supports hypothesis-based directional changes in accordance with the expected mechanism of action. <b>Disclosure:</b> Dr. Palumbo has received personal compensation for serving as an employee of BioVie. An immediate family member of Dr. Palumbo has received personal compensation for serving as an employee of Merck Research Laboratories. Dr. Palumbo has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for BioVie. Dr. Palumbo has stock in BioVie. An immediate family member of Dr. Palumbo has stock in Merck Research Laboratories. Dr. Palumbo has received intellectual property interests from a discovery or technology relating to health care. Dr. Palumbo has received intellectual property interests from a discovery or technology relating to health care. Dr. Palumbo has received intellectual property interests from a discovery or technology relating to health care. Jeffrey Zhang has received personal compensation for serving as an employee of Princeton Pharmatech. Jeffrey Zhang has received stock or an ownership interest from CalciMedica. Ms. Mahdavi has nothing to disclose. Ms. Venkatraman has nothing to disclose. Mr. Becerra has nothing to disclose. Mr. Haroon has nothing to disclose. Ms. Jordan has nothing to disclose. Ms. Rindner has nothing to disclose. Mr. Surya has nothing to disclose. Dr. KUHN has nothing to disclose. Dr. POURAT has nothing to disclose. Dr. Jordan has stock in Synaptec Network.