Anavex 2–73, developed by Anavex Life Sciences, is a small molecule that activates a protein receptor known as the sigma-1 receptor, which is involved in ensuring that proteins fold correctly in the cell as they are produced.
Anavex 2–73 is thought to target several cellular pathways — including failed protein folding, oxidative stress, mitochondrial dysfunction and inflammation — that are relevant to neurodegenerative and neurodevelopmental diseases, such as Rett syndrome.
Mitochondria are small cellular organelles that provide energy and are known as cells’ “powerhouses.” Oxidative stress is an imbalance between the production of free radicals and the ability of cells to detoxify them. These free radicals, or reactive oxygen species, are harmful to the cells and are associated with a number of diseases.
The AVATAR (NCT03941444) study, taking place at the Royal Melbourne Hospitals in Victoria, Australia, is currently recruiting patients. Thirty participants will be randomly assigned to take an oral solution of Anavex 2–73 (18 patients) or a placebo (12 patients) every day for seven weeks. Those who complete the study and show a good safety and tolerability profile will be eligible to continue to take Anavex 2–73 in an open-label extension study.
Preclinical studies using mouse models of Rett syndrome (which have mutations in the MECP2 gene that resemble the human disease) treated with Anavex 2–73 showed that the treatment improved motor and reflex responses to external auditory stimulation compared to placebo. The mice also had better balance and gait patterns.
Anavex 2–73 has been awarded orphan drug status by the U.S. Food and Drug Administration as a potential treatment for Rett syndrome.
”Rett syndrome is a devastating disease for patients and families, for which there are currently no treatments that improve the course of the disease. There is an urgent need for high quality, evidence-based treatments for Rett syndrome patients,” Christopher U Missling, PhD, president and CEO of Anavex said in a press release.
“We are excited to announce the first patient dosed in our AVATAR trial of ANAVEX®2–73 for Rett syndrome,” Missling added. “We have made great effort to develop a patient-centric clinical trial, using our learnings from broad dialogue with the Rett syndrome community.”
Anavex 2–73 is currently being evaluated in another Phase 2 trial (NCT03758924) that is being conducted at three clinical sites in the U.S., with the support of the International Rett Syndrome Foundation. The trial is still recruiting participants.