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Investigational Oral Agent Significantly Reduces Alzheimer Disease Biomarkers
After 12 months of treatment with investigational oral agent ALZ-801 (valiltramiprosate), patients with early Alzheimer disease demonstrated statistically significant and clinically relevant plasma biomarker reduction in addition to previously reported preservation of brain volume and positive memory effects, biopharmaceutical company Alzheon Inc. recently announced.
ALZ-801 is in phase 3 development as a potential disease modifying treatment for Alzheimer disease that blocks the formation of neurotoxic soluble beta amyloid (Aβ) oligomers that cause cognitive decline.
The ongoing phase 2 biomarker trial enrolled 84 patients with early Alzheimer disease who carry either the APOE4/4 or APOE3/4 genotype. Participants received oral ALZ-801 265 mg twice daily.
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Among the 75 patients who completed the week 52 visit, ALZ-801 demonstrated a significant 41% reduction from baseline in plasma phosphorylated tau181 (p-tau181) at 52 weeks. In addition, ALZ-801 significantly reduced the plasma p-tau181/Aβ42 ratio by 37%.
“Across many trials of anti-amyloid treatments, p-tau181 has emerged as a consistent plasma biomarker that correlates with clinical benefit,” said Kaj Blennow, MD, PhD, professor of clinical neurochemistry, University of Gothenburg, Sweden, and a member of Alzheon’s scientific advisory board and developer of the p-tau181 assay. “Upon analysis of the plasma p-tau181 data in our laboratory, we have observed an unprecedented reduction in this leading biomarker of Alzheimer’s pathology in patients taking ALZ-801 tablet for 12 months. This suggests a downstream effect on neuronal function and the potential for clinical efficacy of this novel treatment.”
ALZ-801 showed robust plasma p-tau181 reductions at weeks 13, 26, and 52 that corresponded with previously observed preservation of hippocampal volume and improvements in memory tests. According to Alzheon, the early p-tau181 effects are enabled by a 40% brain penetration of ALZ-801 compared with approximately 1% brain penetration of plaque-clearing antibodies.
“Combined with preservation of brain hippocampal volume and a favorable safety profile with no events of vasogenic edema, these new biomarker data and their positive correlations with cognitive benefits further validate the disease modifying effects of ALZ-801 in Alzheimer’s patients,” said Martin Tolar, MD, PhD, founder, president, and CEO of Alzheon.
“Importantly, rather than slowing the cognitive decline of patients as seen in trials with other agents, subjects treated with ALZ-801 demonstrated cognitive gain from baseline status on memory tests and maintained their cognitive skills over 1 year. These well-differentiated results position ALZ-801 to potentially become the first oral agent that can slow or even stop and prevent Alzheimer’s pathology in patients and healthy individuals at risk for the disease.”
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