Positive findings from a phase 2b/3 study investigating blarcamesine, an investigational agent, demonstrated efficacy among patients with early Alzheimer disease.
Newly announced findings from a follow-up analysis to the phase 2b/3 study (NCT03790709) assessing blarcamesine (Anavex Life Sciences), an investigational therapy, demonstrated a significant reduction in pathological amyloid-ß levels in plasma, as well as a significant slowing in the rate of pathological brain atrophy on MRI scans in treated patients with early Alzheimer disease (AD). According to Anavex, blarcamesine is one of the first therapies to demonstrate efficacy on biomarkers of neurodegeneration and may slow cognitive decline among patients with AD.1
In the study, blarcamesine-treated patients showed significant increases in validated biomarkers of amyloid-ß pathology, plasma Aβ42/40 ratio (P = .048), further demonstrating the agent’s strong antiamyloid effect. Additionally, MRI findings showed significant reduction in brain volume loss, including whole brain (P = .0005), when blarcamesine was comparedwith placebo.
“There is hope that new therapies for Alzheimer that target the disease beyond amyloid that may slow progression of the disease for many people with the earliest forms of the disease,” Marwan Noel Sabbagh, MD, professor of neurology and chairman of the Scientific Advisory Board said in a statement.1 “The advantage of blarcamesine (ANAVEX2-73) is that it is a small oral molecule that exerts clinical benefits on cognition and neurodegeneration and could be appealing because of its route of administration and excellent safety profile.”
The trial was a multicenter, randomized, double-blind, placebo-controlled, phase 2b/3 study that enrolled 508 participants with early symptomatic AD. The participants, recruited from 52 medical research centers and hospitals in 5 countries, were randomized to receive blarcamesine (n = 338) or placebo (n = 170) oral capsules once daily for 48 weeks. The Alzheimer’s Disease Assessment Scale-Cognitive (ADAS-Cog) and Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) subscales were used as primary end points to assess the cognitive and functional efficacy of blarcamesine. Using a mixed model for repeated measures, all prespecified clinical end points were analyzed.
The differences in the least-squares mean (LS) change from baseline to 48 weeks between the blarcamesine and placebo groups were −1.783 (95% CI, −3.314 to −0.251) for ADAS-Cog (P = .0226). In addition, at the same time point, the LS difference between the 2 groups were −0.456 (95% CI, −0.831 to −0.080) for Clinical Dementia Rating Scale Sum of Boxes (P = .0175).
“These data are very exciting, particularly in a study that can demonstrate objective slowing of markers of neurodegeneration,” Michael Weiner, MD, professor of radiology and biomedical imaging, medicine, psychiatry, and neurology at the University of California, San Francisco (UCSF) and principal investigator of the Alzheimer's Disease Neuroimaging Initiative (ADNI) said in a statement.1
One of the most common treatment-emergent adverse events in the respective safety population was dizziness, which was transient and mostly mild to moderate in severity. This adverse event was reported in 120 participants (35.8%) during titration and in 76 participants (25.2%) during maintenance with blarcamesine. In comparison, this adverse effect occurred in 10 participants (6.0%) during titration and 9 (5.6%) during maintenance with placebo.
“Alzheimer disease is such a devastating disease that affects tens of millions worldwide, and Anavex’s clinical development is a testament to our determination to follow the science,” Christopher U Missling, PhD, president and chief executive officer of Anavex said in a statement.1 “We like to thank all the people involved in the study for their invaluable contributions and we look forward to advancing blarcamesine as a potential new convenient orally available treatment option for Alzheimer disease.”