Fast track designation is intended to accelerate the development and review of experimental therapies aimed at treating serious or life-threatening conditions, with potential to address an unmet medical need. This designation includes frequent interactions with the FDA, eligibility for accelerated approval, priority review, and rolling submission of a new drug application to accelerate regulatory review.
Anavex Life Sciences is developing Anavex 2-73.
“With no currently approved agents to treat Rett syndrome, patients and their physicians have an urgent need for new therapeutic options,” Christopher U. Missling, PhD, president and CEO of Anavex Life Sciences, said in a press release. “We view this FDA Fast Track designation as continued support that Anavex 2-73 (blarcamesine) has the potential to address this unmet need.”
Anavex 2-73 is an oral, small-molecule activator of the sigma-1 receptor (S1R), a protein that plays a key role in protein folding. By activating S1R, Anavex 2-73 is designed to reduce the buildup of toxic misfolded proteins in nerve cells, as well as brain inflammation, oxidative stress, and mitochondrial impairment.
While mitochondria are cell compartments responsible for producing energy in the body, oxidative stress refers to an overproduction of oxidant molecules, known as reactive oxygen species, relative to the levels of antioxidant defenses in the body.
The FDA’s decision to grant fast track status to Anavex 2-73 was based on preliminary data from a Phase 2 clinical trial, called RS-001 (NCT03758924), recently presented at the 6th Annual European Rett Syndrome Conference in Finland. The study is still recruiting patients in the U.S.
Early findings from the first six patients on daily Anavex 2-73 over seven weeks showed that treatment led to significant improvements in the overall ability to function, assessed by the Clinical Global Impression Scale- Improvement, and lessened symptom severity as assessed by the Rett Syndrome Behavior Questionnaire.
Treatment also lowered the levels of the neurotransmitter glutamate and raised the levels of another neurotransmitter called gamma-aminobutyric acid (GABA) in the blood.
Neutransmitters are molecules that allow nerve cells to communicate. Some make nerve cells more likely to fire an electrical signal and are considered excitatory (glutamate), while others make cells less likely to fire and are inhibitory (GABA). The balance between excitatory and inhibitory neural signals is the basis of communication between nerve cells in the brain, and is disrupted in patients with Rett.
RS-001 is one of three trials — with AVATAR (NCT03941444) in Australia and EXCELLENCE — that form Anavex’s Rett Syndrome program. EXCELLENCE will enroll participants in Australia, with additional clinical sites planned to open globally in the future. The study will compare Anavex 2-73 with a placebo.
Anavex is also exploring the therapy’s potential to treat Parkinson’s and Alzheimer’s and has received a U.S. patent (No. 10,426,754) covering treatment of Alzheimer’s with Anavex 2-73. More recently, the company received a second U.S. patent (No. 10,507,196) covering treatment of Rett syndrome, multiple sclerosis, Angelman syndrome, cerebral palsy, and autism spectrum disorders.