The company is planning a pivotal trial of blarcamesine in Parkinson disease dementia after submitting results of the phase 2 study to the FDA for regulatory guidance.
Anavex Life Sciences announced that its investigational agent blarcamesine, formerly known as ANAVEX 2-73, was found to be safe and well-tolerated in oral doses up to 50-mg once daily in patients with Parkinson disease dementia (PDD) in a proof-of-concept phase 2 controlled trial.1
Results from the international, double-blind, multicenter, placebo-controlled clinical study showed clinically meaningful, dose-dependent, and statistically significant improvements in the Cognitive Drug Research (CDR) computerized assessment system analysis. The full study results are expected to be submitted for presentation at a medical conference and for publication in a peer-reviewed medical journal, according to Anavex.
Principal investigator Jaime Kulisevsky Bojarski, MD, PhD, professor of neurology, and vice-dean, faculty of medicine, Autonomous University of Barcelona, and director of the movement disorders unit, department of neurology, Sant Pau Hospital, said in a statement, "As the first double-blind trial of ANAVEX 2-73 (blarcamesine) in PDD, this proof-of-concept study provides extremely encouraging data. PDD can be debilitating with significant co-morbidities. New therapies are urgently needed to alleviate this suffering and disability.”
In addition to its safe profile, the study confirmed the precision medicine approach of targeting the selective sigma-1 receptor (SIGMAR1) as a genetic biomarker of response to blarcamesine.
Overall, 132 patients with PDD were randomized equally to target doses of 30- or 50-mg blarcamesine or placebo, respectively. In addition to the safety and efficacy of blarcamesine, investigators observed sleep function at Week 8 and Week 14 as well. Patients were then able to enroll in a voluntary 48-week open-label extension study upon completion of the trial, which evaluated the safety, long-term efficacy and changes in gut microbiota with treatment of blarcamesine.
“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 toward urgently needed treatment for this serious complication of Parkinson’s disease,” Dag Aarsland, MD, PhD, professor, and head, department of old age psychiatry, Institute of Psychiatry, Psychology & Neurosciences, King’s College London, said in a statement.
Blarcamesine is an orally available, small-molecule activator of the sigma-1 receptor, which serves as a molecular chaperone and functional modulator involved in restoring homeostasis. The drug is not only being evaluated in patients with PDD, but in other neurodegenerative disorders such as Alzheimer disease (AD), Rett Syndrome, infantile spasms, Fragile X syndrome, and Angelman’s disorder.
While blarcamesine remains in the preclinical phase for infantile spasms, Fragile X syndrome, and Angelman’s, the drug has shown its efficacy in AD and Rett Syndrome in phase 2 and 3 trials, respectively.
In April, Anavex announced results from a phase 2a clinical study (NCT0224451) of blarcamesine in patients with AD. The study, which was the first genome-wide search for biomarkers associated with therapeutic response in AD, found multiple biomarkers with a significant impact on clinical outcomes at the end of the 57-week treatment period.2
Among them included mean plasma concentration of blarcamesine (slope ∆Mini Mental State Examination [MMSE]: P <.041), genomic variants SIGMAR1 p.Gln2Pro (∆MMMSE: P <.039; ∆Activities of Daily Living Score [ADCS-ADL]: P <.063) and COMT p.Leu146fs (∆MMSE: P <.039; ∆ADCS-ADL: P <.063), and baseline MMSE score (slope MMSE: P <.015).3
The researchers analyzed the relationship between all available patient data and efficacy outcome measures with unsupervised formal concept analysis (FCA), integrated in the Knowledge Extraction and Management (KEM) environment. They concluded that this analysis method is a template for the identification of patient selection markers in early therapeutic development for neurologic disorders.
Findings from the phase 2s study were the basis for the testing of potential patient selection markers for the ongoing phase 2b/3 AD study (NCT03790709), which is expected to conclude in Q4 of 2021.
Anavex also recently announced the completion of the phase 2 study in patients with Rett syndrome. The study included 31 patients who were treated with blarcamesine across a 7-week treatment period. Topline results are expected to be released sometime in Q4 of 2020.4