Latest Trial Results of Anavex 2-73 ‘Very Promising’

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by Forest Ray PhD |

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Anavex 2-73 clinical trial

Clinical improvements with Anavex 2-73 (blarcamesine) correlated with activation of the SIGMAR1 gene, which provides instructions for making the protein targeted by the investigational Rett syndrome therapy, in a Phase 2 study.

The sigma-1 receptor, or SIGMAR1, has been associated with helping nerve cells adapt to experience and injury, and its activation may serve to compensate for the effects of neurological disorders such as Rett.

Based on this result, Anavex Life Sciences, the experimental treatment’s developer, plans to discuss a path toward regulatory approval with the U.S. Food and Drug Administration (FDA).

“The biomarker-driven clinical evidence is very exciting and opens the possibility of successful treatment for both adults and children with Rett syndrome and early interventions for modifying the course of the disease,” Walter E. Kaufmann, MD, the study’s principal investigator and Anavex’s chief medical officer, said in a press release.

The double-blind Phase 2 trial (NCT03758924) evaluated the safety, pharmacological profile, and efficacy of Anavex 2-73 among 31 adult women with Rett syndrome. Participants received once-daily doses of either 5 mg Anavex 2-73 — an orally-administered liquid — or a placebo for seven weeks.


Anavex 2-73 is designed to reduce cellular stress by activating SIGMAR1, which helps proteins fold into their correct, functional shapes.

Trial results published late last year indicated that approximately two-thirds of those receiving Anavex 2-73 (66.7%) saw statistically significant reductions in several of the syndrome’s characteristic behaviors. Those behaviors include general mood, breathing, hand behavior, and repetitive face movements, as measured by the Rett Syndrome Behaviour Questionnaire (RSBQ), the trial’s key efficacy measurement.

Disease severity also declined significantly among those treated with the experimental medication, with 86.7% of treated individuals showing sustained improvements, as assessed by the Clinical Global Impression Improvement Scale (CGI-I).

Compared to placebo, a pre-specified group of participants with the normal version of SIGMAR1 achieved a mean 14.5 point RSBQ benefit and a mean 12.9 point improvement in the Anxiety, Depression, and Mood Scale (ADAMS), measuring anxiety and mood symptoms in individuals with intellectual disability.

The ADAMS improvements were balanced across all subscales, including manic/hyperactive behavior, depressed mood, social avoidance, general anxiety, and obsessive compulsive behavior.

Notably, increases in the levels of SIGMAR1 messenger RNA — an intermediate molecule between DNA and protein — correlated with clinical efficacy as measured by both RSBQ and CGI-I.

“Despite the challenges of the older age of the cohort (patients were on average 24 years of age) and the relatively low dose (5 mg daily), Anavex 2-73 demonstrated clinically meaningful improvements in outcome measures evaluating multiple impairments, which are supported by correlations with objective biomarkers,” Kaufmann said. “The outcome of this trial is very promising in terms of both safety and clinical improvement.”

Added Christopher U. Missling, PhD, Anavex’s president and CEO: “These are strong and consistent data demonstrating biomarker-correlated rapid and clinically meaningful improvements in key measures of Rett syndrome symptoms in the ANAVEX 2-73 treatment group compared to placebo.”

Anavex 2-73 currently holds fast track designation, rare pediatric disease designation, and orphan drug designation from the FDA for the treatment of Rett syndrome.

It also is being evaluated in two other clinical trials. The Phase 2 AVATAR trial (NCT03941444) continues to enroll women with Rett in Australia and the U.K., and the Phase 2/3 EXCELLENCE  trial (NCT04304482) in girls with Rett, ages 5 to 18.