Blarcamesine slows clinical decline in Alzheimer’s disease

Key takeaways:

• Blarcamesine improved scores on Alzheimer’s-specific quality-of-life metrics by as much as 50%.
• Treatment was safe and well-tolerated with few recorded adverse events.

Treatment with oral blarcamesine for older adults with Alzheimer’s disease led to significant slowing of clinical decline compared with placebo at 48 weeks, according to new research presented at CTAD.

“We believe the scalable and convenient features of blarcamesine could reduce crucial barriers within the currently complex health care ecosystem for Alzheimer's disease and provide broader access to a diverse population,” Christopher U. Missling, PhD, president and CEO of Anavex, said in a release related to the study.

The researchers, led by Marwan Noel Sabbagh, MD, FAAN, vice chairman for research and professor in the department of neurology at Barrow Neurological Institute in Phoenix, sought to examine the safety and efficacy of blarcamesine (Anavex Life Sciences), a once-daily, oral small molecule that triggers SIGMAR1, removing misfolded proteins that are consistent with AD pathology.

Their global, randomized, double-blind, placebo-controlled, parallel-group, multicenter 48-week (AD-004) phase 2b/3 study included 508 older adults with a confirmed AD diagnosis via biomarker analysis. Participants were SIGMAR1 wild type carriers and had Mini Mental State Exam scores of 20 to 28.

The participants were randomly assigned on a 1:1:1 basis to receive 30 mg blarcamesine (n = 154; 51.9% men), 50 mg blarcamesine (n = 144; 52.1% men) or placebo (n = 164; 50% women) once per day. Following the treatment regimen, participants were eligible to enroll in a 96-week open-label extension study (ATTENTION-AD).

The AD-004 study’s co-primary endpoints were change from baseline to week 48 in scores on the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13) and Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) metrics, with improvement in Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) score as the chief secondary endpoint.

The results showed that blarcamesine slowed clinical decline for the overall study population as measured by the ADAS-Cog13 by 36.3% and in the CDR-SB by 27.6%. Clinical decline in SIGMAR1 wild type carriers slowed by 49.8% in the ADAS-Cog13 and by 33.7% in the CDR-SB at week 48.

The researchers additionally found that blarcamesine was generally safe, with few adverse events reported, the majority of which were mild and transient in nature, corrected by adjusting titration and dosing times. Treatment-emergent adverse events were recorded in the first 24 weeks, also related to titration.

“These data are very exciting, particularly featuring blarcamesine’s novel upstream mechanism of action, enhancing autophagy through SIGMAR1 activation, a key clearance mechanism that removes protein aggregates and misfolded proteins across the Alzheimer's disease continuum,” Juan Carlos Lopez-Talavera, MD, PhD, head of research and development of Anavex, said in the release.

Reference:

Anavex’s blarcamesine achieves pre-specified efficacy in phase 2b/3 Alzheimer’s trial: Data presented at CTAD conference 2024. https://www.anavex.com/post/anavex-s-blarcamesine-achieves-pre-specified-efficacy-in-phase-iib-iii-alzheimer-s-trial-data-prese. Published Oct. 31, 2024. Accessed Nov. 11, 2024.