Abstract for Saturday March 9th, 2024 at the ADPD 2024 in Lisbon, Portugal. Times appear to be local.
BLARCAMESINE IN EARLY SYMPTOMATIC ALZHEIMER DISEASE PHASE 2B/3 RANDOMIZED CLINICAL TRIAL
Presenter
• Timo Grimmer (Germany)
Lecture Time
09:10 - 09:25
• Abstract
AIMS
To assess in early Alzheimer’s disease (AD) patient’s efficacy and adverse events of blarcamesine
(ANAVEX®2-73), an orally available, small-molecule activator of the sigma-1 receptor (SIGMAR1) designed
to exert neuroprotection through restoration of cellular homeostasis.
METHODS
ANAVEX®2-73-AD-004 48-week study was an international, double-blind, multicenter, placebo-controlled
Phase 2b/3 clinical study. 508 patients with AD were randomized to blarcamesine or placebo. The clinical
outcomes (primary, secondary, and exploratory) included ADAS-Cog13, ADCS-ADL, CDR-SB, and CGI-I,
which were analyzed using a mixed model for repeated measures (MMRM) and biomarkers from the A/T/N
spectrum, plasma Aß42/40 ratio and brain volume measured by MRI.
RESULTS
The trial was successful, since the differences in the least-squares mean (LSM) change from baseline to 48
weeks between the blarcamesine and placebo groups were -1.783 [95% CI, -3.314 to -0.251]; (P = 0.0226)
for ADAS-Cog13, and -0.456 [95% CI, -0.831 to -0.080]; (P = 0.0175) for CDR-SB in patients with early AD.
In addition, validated biomarkers of amyloid beta pathology, plasma Aß42/40 ratio increased significantly (P
= 0.048), demonstrating strong anti-amyloid effects of blarcamesine in Alzheimer’s disease patients, while
MRI revealed significant reduction in brain volume loss, including whole brain (P = 0.0005), comparing
treatment to placebo.
CONCLUSIONS
Among participants with early symptomatic AD, blarcamesine was generally safe, well tolerated and
significantly slowed clinical progression at 48 weeks, which is also corroborated by biomarkers from the
A/T/N spectrum, including plasma Aß42/40 ratio increase and reduction of brain atrophy in several key
regions of the brain measured by MRI.
ClinicalTrials.gov Identifier: NCT03790709.
