Blarcamesine Treatment Shows Clinical and Biomarker Improvements in Parkinson Disease Dementia
In a clinical trial (NCT03774459) of blacarmesine (Anavex 2-73; Anavex Life Sciences, New York, NY) for Parkinson disease dementia (PDD), clinical improvements in motor and nonmotor symptoms were seen. There was also evidence of relevant biomarker changes.
Individuals treated with 50 mg/day blacarmesine vs placebo had a -14.51-point change (reflecting improved symptoms) in total score on the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) total score (P=.034).
Clinical improvements were seen across all domains of the MDS-UPDRS scale, including nonmotor and motor experiences of daily living, motor examination, and motor complications. These improvements were clinically relevant corresponding to a relative improvement of 18.9% over 14 weeks. Cognitive improvements were assessed by the Cognitive Drug Research (CDR) computerized assessment system and seen with blacarmesine vs placebo in domains of attention (reaction [P=.039] and vigilence [P=.008]) and episodic memory (P=.047).
Blacarmesine targets sigma 1 and muscarinic receptors; in this study, treatment with blacarmesine, MDS-UPDRS scores, and cognitive endpoints all correlated with changes in sigma 1 receptor mRNA expression (P=.035) over the course of treatment. These data suggest that sigma 1 mRNA levels could be used as a biomarker for the effects of treatment.
"PDD is a debilitating disorder with significant comorbidities and there has not been a mechanistically novel medication approved for PDD in over 20 years,” said Jaime Kulisevsky, MD, PhD, professor of neurology, University of Barcelona. “Hence, new therapies are urgently needed to alleviate this suffering and disability. I am impressed with the robust improvement of the MDS-UPDRS across all sub-score parts 1-4 coupled with the biomarker correlated outcome measures and I support the implementation of the Anavex 2-73 Phase 3 studies in Parkinson disease and Parkinson disease dementia, respectively.”
Blacarmesine was well-tolerated in oral doses up to 50 mg once daily. Study participants were allowed to be on a stable regimen of anti-Parkinson's disease medications (including levodopa, dopamine agonists, MAO-B inhibitors, or entacapone). Treatment with cholinesterase inhibitors, rivastigmine, donepezil, and galantamine was also permitted.
These data are being presented at the AD/PD 2022 International Conference on Alzheimer’s & Parkinson’s Diseases in Barcelona, Spain and virtually March 15-20, 2022.