Anavex Life Sciences Corp. announced that long-term clinical study results from the U.S. ANAVEX(R) 2-73-RS-001 (NCT03758924) study demonstrate disease modifying effect of ANAVEX(R) 2-73 (blarcamesine) for adult patients with Rett syndrome. Usually, symptomatic therapies treat the symptoms of the disease but do not address the underlying cause of the disease.

Disease-modifying therapies target the underlying cause of the disease. ANAVEX(R) 2-73 (blarcamesine) is an orally available, small-molecule activator of the sigma-1 receptor (SIGMAR1) which, data suggest, is pivotal to restoring cellular homeostasis and promoting neuroplasticity.(1) In the U.S. ANAVEX(R) 2-73-RS-001 trial, of all 25 patients who both started and completed the randomized, double- blind, placebo-controlled study, 24 patients voluntarily enrolled in the 12-week open label extension (OLE) study, receiving once daily oral liquid ANAVEX(R) 2-73 (blarcamesine) formulation for further evaluation of long-term safety, tolerability, and effectiveness of ANAVEX(R) 2-73 (blarcamesine) in patients with Rett syndrome. The 12-week extension study was subsequently further extended to 36 weeks.

The effect of ANAVEX(R) 2-73 (blarcamesine) in the double-blind part of the U.S. ANAVEX(R) 2-73-RS-001 study was maintained in the open label 12-week extension study. Results from pharmacometric modeling of the full clinical data (i.e., from baseline of the double-blind study to the end of the open label extension study) indicates that the data are best characterized by a combined symptomatic and disease modifying drug effect model. Meaning that ANAVEX(R) 2-73 (blarcamesine) exhibited both symptomatic and disease modifying effects in the treatment of Rett syndrome in a clinical setting.

Patients assigned first to ANAVEX(R) 2-73 (blarcamesine) in the double-blind part of the study and who continued on ANAVEX(R) 2-73 (blarcamesine) during the open label extension (OLE) study had a statistically significant (p = 0.01147) reduction in disease severity when compared with patients assigned first to placebo in the double-blind part of the study and who then received ANAVEX(R) 2-73 (blarcamesine) during the open label extension (OLE) part of the study -- a criterion for classification as a disease modifying agent. Continued improvement from the drug, as measured with the Rett Syndrome Behavior Questionnaire (RSBQ) total score,(2) was observed from the start of the double-blind study to the end of the open label extension part for patients continuing on ANAVEX(R) 2-73 (blarcamesine). Patients previously on placebo, who switched to ANAVEX(R) 2-73 (blarcamesine) in the OLE part of the study experienced improvement during the OLE part.

Additionally, disease progression, which is defined as change in Rett syndrome disease severity with time, was also reduced with long-term treatment with ANAVEX(R) 2-73 (blarcamesine). Patients assigned first to ANAVEX(R) 2-73 (blarcamesine) in the double-blind part of the study and who continued on ANAVEX(R) 2-73 (blarcamesine) during the open label extension (OLE) study had a statistically significant (p = 0.01752) reduction in disease progression when compared with patients assigned first to placebo in the double-blind part of the study and who then received ANAVEX(R) 2-73 (blarcamesine) during the open label extension (OLE) part of the study -- a criterion for classifying a drug as a disease modifying agent. Patients assigned to ANAVEX(R) 2-73 (blarcamesine) at the start of the double-blind study experienced more benefit of drug effect than could be explained by symptomatic benefit alone -- hence, ANAVEX(R) 2-73 (blarcamesine) exhibited both symptomatic and disease modifying effect.

The reduction in annual rate of disease progression for those patients, who continued on ANAVEX(R) 2-73 (blarcamesine) was over 3-fold greater, relative to those who switched from placebo to ANAVEX(R) 2-73 (blarcamesine): Ratio of reduction in annual rate of disease progression = 3.17 (Reduced disease progression rate [Double-blind Part/OLE -- ANAVEX(R) 2-73/ANAVEX(R) 2-73] = -1.383/year; Reduced disease progression rate [Double-blind Part/OLE -- Placebo/ANAVEX(R) 2-73] = -0.4357/year). Anavex plans to submit the data for publication in a peer-reviewed medical journal. ANAVEX(R) 2-73 (blarcamesine) has previously received Fast Track designation, Rare Pediatric Disease designation and Orphan Drug designation from the FDA for the treatment of Rett syndrome.