FDA Grants Rare Pediatric Disease Designation to Anavex 2-73 for Rett Syndrome

The U.S. Food and Drug Administration (FDA) has granted rare pediatric disease designation to Anavex 2-73 (blarcamesine) for the treatment of Rett syndrome.

This designation provides priority review to investigational treatments that have the potential to provide clinically meaningful benefits in serious rare diseases mainly affecting individuals younger than 18.

If the FDA ultimately approves Anavex 2-73, the treatment’s developer — Anavex Life Sciences — may quality for a voucher redeemable for priority review of a subsequent application for a different product. This voucher program is an incentive to develop treatments for rare pediatric diseases that might otherwise not be profitable.

“We are pleased to have received the rare pediatric designation from the U.S. FDA for [Anavex 2-73] for young patients with Rett syndrome,” Christopher U. Missling, PhD, Anavex’s CEO, said in a press release. “This designation for [Anavex 2-73] underscores the significant unmet medical need for patients with this genetic disease.”

Anavex 2-73 is an investigational oral therapy that activates the sigma-1 receptor (S1R), a protein involved in the correct folding of other proteins. S1R activation leads to reduced toxic accumulation of misfolded (altered shape) proteins, less dysfunction in mitochondria (which provide energy to cells), as well as decreased oxidative stress and neuroinflammation, all involved in Rett syndrome.

Oxidative stress is an imbalance between the production of free radicals — potentially harmful molecules associated with several diseases — and the generation of antioxidant defenses.

Preclinical work showed that Anavex 2-73 improved motor skills, acoustic responses, and visual acuity in a mouse model of Rett syndrome, which supported the therapy’s Phase 2 clinical program in people with the disorder.

Two ongoing Phase 2 studies are evaluating the safety and effectiveness of Anavex 2-73 in Rett patients in the U.S. (RS-001; NCT03758924, still enrolling) and in Australia (AVATAR; NCT03941444). Together, these trials will include up to 51 women with Rett syndrome.

Preliminary results from the first six participants in the RS-001 study showed that treatment with Anavex 2-73 was well-tolerated and significantly eased Rett symptoms. These benefits correlated with meaningful changes in blood levels of crucial biomarkers of the disorder.

Anavex also plans to launch the EXCELLENCE study to compare the safety and effectiveness of Anavex 2-73 to a placebo in about 69 children and adolescents (ages 5–18) with Rett syndrome.

The trial is expected to open in Australia in the coming months, followed by additional clinical sites globally. More information is available here.

“Our goal is to advance a potential treatment for Rett syndrome in order to bring medicines to patients as soon as possible,” Missling said.

The FDA also previously granted orphan drug designation to Anavex-2-73 for the treatment of Rett syndrome. In Europe, the Committee for Orphan Medicinal Products, an arm of the European Medicines Agency, has recommended a similar designation from the European Commission.

These designations are intended to accelerate the development of Anavex-2-73 by providing regulatory support and financial benefits, and also to ensure marketing exclusivity for a period of time (seven years in the U.S. and 10 years in the European Union) pending approval.

Anavex is also exploring the therapy’s potential in Alzheimer’s and Parkinson’s.