Anavex Life Sciences' oral blarcamesine (ANAVEX®2-73) has shown promising results in slowing the progression of early Alzheimer's disease, according to data from the ATTENTION-AD trial. The study, a continuation of the ANAVEX®2-73-AD-004 double-blind trial, evaluated the long-term effects of blarcamesine on cognition and function over three years. The findings suggest that continuous treatment with blarcamesine significantly reduces clinical decline and provides meaningful benefits for patients with early Alzheimer's.
The ATTENTION-AD trial included an open-label extension (OLE) lasting 96 weeks for participants in North America and Europe, and up to 144 weeks for those in Australia. The study aimed to assess the safety, tolerability, and long-term efficacy of blarcamesine in patients with early Alzheimer's disease.
Sustained Cognitive Benefits
Results from the delayed-start analysis demonstrated a significant difference in ADAS-Cog13 scores between early and late treatment groups at Week 144 (LS mean difference -2.70, P = 0.0348), favoring the early start group. This treatment difference continued to increase up to Week 192 (LS mean difference -3.83, P = 0.0165), suggesting that earlier initiation of blarcamesine leads to greater stability in cognitive function. According to Prof. Dr. Timo Grimmer, MD, "Long-term clinical ATTENTION-AD study results support the importance of continued long-term blarcamesine treatment."
Similarly, the delayed-start analysis for ADCS-ADL showed numerically favorable results for the early start group over the late start group at Week 144 (LS mean difference +2.32, P = 0.125). The treatment difference continued to increase up to Week 192 and reached statistical significance (LS mean difference +4.30, P = 0.0206).
Safety and Tolerability
Blarcamesine exhibited a favorable safety profile, with most adverse events being mild to moderate in severity and primarily linked to the initial titration phase. No severe or life-threatening adverse events were attributed to blarcamesine, and there were no deaths related to the drug. The most frequent treatment-emergent adverse event (TEAE), dizziness, was effectively managed by adjusting the titration schedule, reducing its frequency from 25.2% in the ANAVEX®2-73-AD-004 trial to 9.6% in the ATTENTION-AD trial.
Mechanism of Action and Clinical Implications
Blarcamesine is a small molecule administered orally once daily, demonstrating clinically meaningful improvement over 48 weeks with primary endpoint ADAS-Cog13 score being larger than 2 points. The Phase IIb/III trial data, recently published in The Journal of Prevention of Alzheimer's Disease (JPAD), highlights blarcamesine's potential to target upstream Alzheimer's disease pathology through autophagy enhancement via SIGMAR1 activation. This mechanism could offer a complementary or alternative approach to injectable anti-beta amyloid drugs.
Juan Carlos Lopez-Talavera, MD, PhD, Head of Research and Development of Anavex, stated, "These results demonstrate that diagnosing and treating people earlier in the progression of Alzheimer's disease may lead to greater clinical benefit." The company is currently aiming to advance blarcamesine as a potential treatment option for Alzheimer's disease, with its Marketing Authorization Application (MAA) under review by the EMA.
Ongoing Compassionate Use Program
Currently, 74 participants are receiving blarcamesine within the Compassionate Use Program, with some continuing treatment for over 9 years. No severe or life-threatening adverse events have been attributed to blarcamesine in this program.
