Daily Alzheimer’s pill slows brain shrinkage, boosts cognition
Analysis of trial data shows blarcamesine benefits sustained over time
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The benefits seen in people with early Alzheimer’s disease after a year of treatment with blarcamesine (Anavex 2-73) were sustained over nearly three years, according to new analysis from the treatment’s developer, Anavex Life Sciences.
Patients treated with the investigational oral medication in a Phase 2b/3 study had less loss of brain volume, a marker of neurodegeneration, along with improvements in measures of cognition, daily function, and disease severity, one-year data showed.
A new analysis from that trial and its long-term extension showed that those trends continued, and patients also experienced slower disease progression over three years. The results were presented in an oral session titled, “Advancing Alzheimer’s Disease Care: Convenience for Both Patients and Families with Oral Blarcamesine with Long-term Time Saved,” at the 2026 International Conference on Alzheimer’s and Parkinson’s Diseases, held March 17–21 in Copenhagen and online.
“These results indicate that blarcamesine’s clinical effects are biologically coherent with MRI‑based measures of neuroprotection,” Christopher U. Missling, PhD, president and CEO of Anavex, said in a company press release. “The consistent relation between structural preservation of brain volume and functional outcomes further drives our dedication to developing a novel disease-modifying Alzheimer’s treatment with our oral blarcamesine.”
Alzheimer’s is caused by the buildup of toxic clumps of misfolded proteins in brain cells, which disrupts their function and eventually leads to their death. As these cells are lost over time, connections between them break down, leading to Alzheimer’s symptoms of progressive brain shrinkage and impaired cognitive function.
Daily capsule aims to boost toxin-removing process
Given as a once-daily oral capsule, blarcamesine is designed to enhance autophagy, a recycling process cells use to remove unneeded or toxic proteins, including those involved in Alzheimer’s. By doing so, the therapy aims to protect brain cells and slow disease progression.
The global Phase 2b/3 trial, Anavex 2-73-AD-004 (NCT03790709), evaluated blarcamesine in 508 patients, ages 60-85, with mild cognitive impairment due to Alzheimer’s. Participants were randomly assigned to receive daily doses of 30 mg or 50 mg of blarcamesine or a placebo for 48 weeks (about one year).
Results showed that both doses significantly slowed cognitive decline, as measured by the Alzheimer’s Disease Assessment Scale-Cognition (ADAS-Cog13), and cognitive and functional worsening, as assessed with the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB).
The therapy also significantly reduced brain shrinkage in several key regions. According to updated data, these include the whole brain (37.7%), total grey matter (63.5%), and the temporal lobe (69.2%) — a region critical for memory and language.
After completing the trial, participants could enter an open-label extension study, ATTENTION-AD Anavex 2-73-AD-EP-004 (NCT04314934), in which all patients received blarcamesine and were monitored for long-term outcomes.
After nearly four years, patients who started treatment earlier maintained significantly better cognitive scores on ADAS-Cog13 than those who initially received a placebo. Similar benefits were observed in daily functioning, as measured by the Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale. Overall, the therapy was well tolerated, with most side effects mild to moderate. The most common drug-related side effect was dizziness, which did not typically last long.
The new analyses from these trials showed that reductions in brain atrophy across all three key regions after about one year of treatment with blarcamesine were consistently associated with improvements in cognition (ADAS-Cog13), daily functioning (ADCS-ADL), and disease severity (CDR-SB).
In a subgroup of patients known as ABCLEAR3, a genetically defined subgroup whose specific genetic profile is associated with an enhanced response to blarcamesine, the association between brain volume changes and ADAS-Cog13 was even stronger, about 78% higher than in the overall study population.
Over nearly three years of follow-up, treatment with blarcamesine delayed disease progression by 77 weeks (nearly 18 months) compared with a matched external control group from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), a large, long-running research database that tracks disease progression in people with Alzheimer’s who are not receiving the therapy.
“The patient-friendly oral administration, the manageable side effects, and the clinical efficacy — particularly in the genetically defined ABCLEAR3 population — make blarcamesine, in conjunction with the associated biomarker signal, a promising drug candidate for patients with early-stage Alzheimer’s disease,” said Timo Grimmer, MD, a member of the Anavex scientific advisory board and national coordinating investigator for the Anavex 2-73-AD-004 study. Grimmer presented the data at the conference.
Grimmer, who presented the results at the conference, said researchers believe “these new results will contribute to the growing body of scientific data demonstrating the long-term beneficial effect of blarcamesine in early Alzheimer’s disease.”
Anavex is also exploring blarcamesine’s potential in other neurological diseases, including Parkinson’s, Rett syndrome, and fragile X syndrome.
