Anavex 2-73 (blarcamesine), a potential oral therapy to slow cognitive decline due to Alzheimer’s and other neurological disorders, was found to be safe and to lead to clinically meaningful, dose-dependent improvements in cognition in people with Parkinson’s disease dementia (PDD) treated in a Phase 2 trial.
Anavex Life Sciences, which is developing the therapy and sponsored the ANAVEX 2-73-PDD-001 (NCT03774459) study, is now planning to open a pivotal Phase 3 trial of Anavex 2-73 in PDD patients, with regulatory guidance from the U.S. Food and Drug Administration.
“Given the limited options of adequate treatments for Parkinson’s disease dementia, and the safety concerns and modest or uncertain efficacy of currently used off-label treatments, the Anavex 2-73 (blarcamesine) study results represent a meaningful step forward,” Dag Aarsland, MD, PhD, a professor and head of the Department of Old Age Psychiatry at the Institute of Psychiatry, Psychology & Neuroscience at King’s College London, said in a press release.
Initially developed as a potential disease-modifying therapy for Alzheimer’s, Anavex 2-73 is an orally available small molecule that activates the sigma-1 receptor (SIGMAR1), which is responsible for regulating cellular activity and maintaining the natural balance of brain cells.
By activating SIGMAR1, whose levels are diminished in the brains of people with Parkinson’s and Alzheimer’s, Anavex 2-73 is thought to help lower oxidative stress, neuroinflammation, and the buildup of beta-amyloid and tau proteins. All are known to contribute to disease progression.
The therapy’s safety, tolerability, and initial efficacy are being investigated in 132 people with dementia linked to Parkinson’s disease in ANAVEX 2-73-PDD-001, a multicenter, double-blind, and placebo-controlled study that served as the treatment’s proof of concept.
Enrolled PDD patients, ages 50 to 85, were randomly assigned to either a medium (30 mg) or high (50 mg) dose of Anavex 2-73, or to a placebo, for 14 weeks.
Treatment effects on patients’ cognition, a primary study goal, were measured using the cognitive drug research computerized assessment system, which tests such skills as choice reaction time, vigilance, and the sensitivity and speed of digit, word and picture recognition. Safety, the trial’s other primary goal, was reviewed in terms of adverse events.
Secondary goals included changes in patients’ motor abilities and sleep quality.
Those completing the trial have the option to continue or start treatment with Anavex 2-73 in its 48-week extension, ANAVEX 2-73-PDD-EP-001 (NCT04575259).
This open-label study will assess the oral medication’s long-term safety and tolerability as primary goals. Measures of efficacy, again taken as changes in sleep quality, cognition and motor skills, as well as its possible changes in the number and composition of gut bacteria, are secondary objectives.
In the main Phase 2 trial, Anavex 2-73 was found to be safe and well tolerated at doses up to 50 mg once daily.
Treatment also led to meaningful and dose-dependent cognitive improvements. Detailed data on findings from ANAVEX 2-73-PDD-001 will be given at a scientific conference and published in a medical journal, Anavex Life Sciences stated in its release.
Additionally, the trial validated SIGMAR1 targeting as a therapeutic approach for patients with significant cognitive impairments.
“Our strategy to advance Anavex 2-73 (blarcamesine) with focus on Precision Medicine has been validated in this study of patients with significant cognitive impairment and we are looking forward to the next clinical data readout of ANAVEX 2-73 in Rett syndrome and Alzheimer’s disease, indications where cognitive impairment is also prevalent,” said Christopher Missling, PhD, president and CEO of Anavex.
The Phase 2 PDD trial, which took place at sites across Spain and in Australia, was supported by the Michael J. Fox Foundation for Parkinson’s Research and León Research.
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