Anavex Life Sciences’ investigational drug candidate ANAVEX2-73 led to improvements in clinical efficacy endpoints, including cognitive and non-cognitive measures, in a phase 2 Parkinson’s disease study.
The phase 2 trial enrolled 132 patients with Parkinson’s disease, with candidates randomised equally to receive either 30 mg, 50 mg ANAVEX2-73 or placebo, respectively.
The study found that the treatment resulted in a significant increase in mRNA expression of the SIGMAR1 (sigma-1 receptor) – the drug’s target biomarker.
Previous data suggests that activation of SIGMAR1 can lead to the restoration of complete housekeeping function in the body, and is key to restoring neural cell homeostasis and promoting neuroplasticity.
Independent research also strengthens the case that SIGMAR1 activation has a beneficial effect as a compensatory mechanism to chronic central nervous system (CNS) diseases.
ANAVEX2-73 is designed to activate SIGMAR1 and is also in development as a treatment for Alzheimer’s disease, Rett syndrome, infantile spasms, Angelman’s syndrome and Fragile X syndrome.
In the phase 2 trial, the boost of SIGMAR1 observed with ANAVEX2-73 treatment correlated with clinical efficacy, showing statistically significant improvements compared to placebo on the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) total score.
The MDS-UPDRS total score improved by -10.98 points in the high-dose ANAVEX2-73 group, while it worsened by 3.53 points in the placebo group from baseline to the end of the trial at 14 weeks.
“This is now the second independent placebo-controlled clinical ANAVEX2-73 phase 2 study to confirm the predictive biomarker of response established with SIGMAR1 mRNA expression. Both ANAVEX2-73-PDD-001 Parkinson’s disease dementia study and the recently reported ANAVEX2-73-RS-001 US Rett syndrome study are persuasively consistent with the proposed mechanism for ANAVEX2-73,” said Christopher Missling, president and chief executive officer of Anavex.
“We believe that the easily accessible predictive biomarker combined with the observed efficacy is a consistent explanation of the efficacy in this second largest CNS indication with unmet medical need. This data further strengthens the foundation of ANAVEX2-73 as a cross-platform CNS drug,” he added.
Following the biomarker-correlating efficacy data from the phase 2 Parkinson’s disease, Anavex is planning to submit the results to the US Food and Drug Administration (FDA) in a bid to seek regulatory guidance for the treatment.