An extension study of a Phase 2 trial investigating Rett syndrome therapy candidate Anavex 2-73 has dosed its first patient.
“We are delighted to provide continuation of Anavex 2-73 treatment for Rett syndrome patients,” Christopher U Missling, PhD, Anavex’s president and CEO, said in a press release.
The open-label, 12-week study will evaluate the long-term safety, tolerability, and clinical benefits of the therapy in women who have completed seven weeks of treatment in the Anavex 2-73-RS-001 study (NCT03758924). Those showing a good safety and tolerability profile are eligible to voluntarily move into the extension study.
All participants will receive the oral liquid formulation of the experimental treatment, given once daily. The extension study may be prolonged beyond the original 12-week duration.
The parent double-blind, placebo-controlled Phase 2 trial is analyzing the safety and clinical benefits of Anavex 2-73 in 15 women, ages 18 to 45 years. It is ongoing in the U.S., and is currently recruiting. More information on the four trial sites, and contacts, can be found here.
Patients in the parent trial are being randomly assigned to receive the potential treatment or placebo. This study is expected to be completed by December 2019.
The start of the U.S. extension study follows the initiation of the AVATAR Phase 2 trial in Australia, which also is assessing Anavex 2-73 in people with Rett syndrome. AVATAR is being conducted at the Royal Melbourne Hospitals in Victoria and is currently enrolling adult participants.
Anavex 2-73 is an engineered small molecule that works by activating the Sigma-1 receptor protein. The potential therapy is thought to help restore cellular balance by ensuring correct protein folding. It also is designed to ease oxidative stress — an imbalance between the production of toxic reactive oxygen species and the cells’ ability to detoxify them – and reduce inflammation. Additionally, Anavex 2-73 is intended to improve the function of nonworking mitochondria, which are cells’ power plants.
The therapy has already received orphan drug designation from the U.S. Food and Drug Administration as a treatment for Rett syndrome.
In a mouse model of the disorder, Anavex 2-73 significantly improved motor and reflex response to external auditory stimulation, compared with placebo. Chronic dosing over 6.5 weeks also led to improvements in balance, gait, motor learning, and muscle strength.
Anavex 2-73 also is being developed as a treatment for Alzheimer’s disease. In a Phase 2 extension study (NCT02756858), it was shown to reduce cognitive decline and improve patients’ abilities to perform daily activities.
Another Phase 2 study (2017-004335-36) will evaluate the efficacy and safety of the treatment for Parkinson’s disease dementia. This trial also will asses Anavex 2-73’s impact on motor function and sleep quality.
In animal models, Anavex 2-73 showed anticonvulsant, anti-amnesic, neuroprotective, and anti-depressant effects, suggesting its potential to treat other neurologic disorders, such as epilepsy.