Anavax2 73 in Phase IIb/III study met primary endpoints for the treatment of mild cognitive impairment due to Alzheimer's disease.- Anavex Life Sciences
Anavex Life Sciences Corp. announced positive topline results from its Phase IIb/III ANAVEX2-73-AD-004 clinical trial of oral ANAVEX2 73 (blarcamesine) for the treatment of mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) and mild AD (collectively known as early AD).
ANAVEX2 73 met the primary endpoints ADAS-Cog and ADCS-ADL and key secondary endpoint CDR-SB with statistically significant results. Next step, in light of this data, is meeting with regulatory authorities to discuss this data in the context of ongoing development with an aim to bring this therapy to patients in Europe, Asia-Pacific, and the U.S.
ANAVEX2 73 (blarcamesine) is an orally available, small-molecule activator of the sigma-1 receptor (SIGMAR1), which, data suggest, is pivotal to restoring neural cell homeostasis and promoting neuroplasticity.
ANAVEX2-73-AD-004 was a randomized, double-blind, multicenter, placebo-controlled 509 patient Phase IIb/III study (randomized 1:1:1 to mid or high dose of ANAVEX2 73 or placebo), for the treatment of early Alzheimer’s disease over 48 weeks. Further analysis of the data remains ongoing, and the Company plans to submit the data for publication in a peer-reviewed medical journal. The open-label extension study ATTENTION-AD will continue to follow participants over a 96 week period.
ANAVEX2 73 treatment met the primary endpoints and reduced clinical decline on the global cognitive and functional scales over 48 weeks in the analysis of the Intent-to-treat (ITT) population. ANAVEX2 73 demonstrated visible improvement in patients with Alzheimer’s disease. Patients treated with ANAVEX2 73 were 84% more likely, to have improved cognition by ADAS-Cog score change of -0.50 points or better from baseline to end of treatment than patients on placebo, Odds Ratio = 1.84 (p = 0.015). On average, patients, who improved cognitively with ANAVEX2 73 treatment, improved by ADAS-Cog cognition score of -4.03 points. ANAVEX2 73 treatment was 167% more likely to improve function compared with placebo, at a clinically meaningful improvement of ADCS-ADL score change of +3.5 points or better, Odds Ratio = 2.67 (p=0.0255). This reflects a robust improved and clinically meaningful outcome in cognition and function from baseline. Additionally, treatment with ANAVEX2 73 statistically significantly reduced cognitive decline, measured with ADAS-Cog, compared to placebo at end of treatment by 45%, representing a treatment difference in mean score change of -1.85 points (p=0.033).
ANAVEX2 73 treatment also met the secondary endpoint of reduction in clinical decline of cognition and function assessed by the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) compared to placebo, by a treatment difference in mean score change of -0.42 points (p=0.040), representing 27% reduction in the ITT population. ANAVEX2 73 (blarcamesine) was generally safe and well tolerated. The incidence of treatment emergent adverse events (TEAEs) was similar in the active and placebo arms with dizziness being the most common TEAE. TEAEs greater than 7.5% threshold were predominantly mild or moderate. No clinically significant changes in vital signs, laboratory values and ECG parameters in active and placebo arms were observed. Safety findings in the study were consistent with the known safety profile of ANAVEX2 73.
In addition to safety and efficacy demonstrated on the primary and key secondary endpoints, a pre-specified analysis of patients without SIGMAR1 gene mutation provides further confidence of the robustness of the SIGMAR1 activation in the treatment of neurodegenerative diseases. Approximately 80% of the total worldwide population lack a SIGMAR1 gene mutation.ANAVEX2 73 was more efficacious in this pre-specified population. This effect is consistent with prior clinical trials of ANAVEX2 73.
“People living with Alzheimer’s disease desperately need new therapies and I am truly impressed with the outcome of this study, which demonstrated reversal of cognitive decline,” said A/Professor Stephen Macfarlane, FRANZCP, Head of Clinical Services at the Dementia Centre, HammondCare and Principal Investigator. “These results complement and are consistent with findings from the previously completed Alzheimer’s disease Phase IIa ANAVEX2 73 trial, which also demonstrated therapeutic effect on cognition and function. ANAVEX2 73 might be a very much needed solution for many patients with Alzheimer’s disease.”
Economic Burden of Alzheimer's Disease: Alzheimer's disease is the most common cause of dementia and the fifth leading cause of death in adults older than 65 years. The estimated total healthcare costs for the treatment of Alzheimer's disease in 2020 were estimated at $305 billion, with the cost expected to increase to more than $1 trillion as the population ages. Most of the direct costs of care for Alzheimer's disease are attributed to skilled nursing care, home healthcare, and hospice care. Indirect costs of care, including quality of life and informal caregiving, are likely underestimated, and are associated with significant negative societal and personal burdens.