(Originally published on ATAI.life on January 16, 2020)
On Monday, GABA Therapeutics commenced dosing for its phase I clinical trial of the anxiolytic etifoxine in Melbourne, Australia. The phase I, two-stage, double-blind, placebo-controlled single and multiple dose study is evaluating the pharmacokinetics, pharmacodynamics, and safety of oral etifoxine in up to 34 normal healthy volunteers.
“Data from this study could provide important insights for a broad range of neurological disorders beyond anxiety and depression.” said Dr. Ian Massey, co-founder and CEO of GABA Therapeutics.
Clinical studies have shown that etifoxine has comparable speed of onset and anxiolytic efficacy as the world’s top two selling benzodiazepines (Xanax® and Ativan®). In contrast, however, etifoxine produces its anxiolytic effects without the side effects of sedation, amnesia, ataxia, and dependence associated with benzodiazepines. Moreover, etifoxine is non-addictive, with a French National Agency for the Safety of Medicines and Health Products pharmacovigilance study reporting that adverse drug effects occurred in just 21 per million patients. The same study found no cases of abuse, misuse, or dependence after analyzing 14 million prescriptions between 2000 and 2012.
Etifoxine appears to have a dual mechanism of action. It acts as a weak allosteric modulator at the GABAa channel acting at a site distinct from the benzodiazepine binding site. Perhaps even more importantly, it also acts at the mitochondrial translocator protein TSPO, leading to increases in endogenous neurosteroids (such as allopregnanolone), which are essential for maintaining healthy brain biochemistry. Neurosteroids can induce potent anxiolytic, antidepressant, anticonvulsant, and analgesic effects, mainly through interaction with the GABA channel, the main inhibitory system in the brain.
Although there is a great deal of clinical experience with etifoxine, little has been published on its pharmacokinetics and effects on neurosteroids in humans. Therefore, GABA’s Australian study will be a key step in building reliable clinical data on Etifoxine’s efficacy and safety.
GABA’s flagship product, GRX-917, the deuterated version of etifoxine, has an identical mechanism of action, biology and pharmacology as etifoxine, but with improved pharmacokinetics. Based on all the data for etifoxine , GRX-917 will be safer and clinically superior to America’s top two drug classes of anxiolytics: SSRIs/SNRIs and benzodiazepines. Additionally, the drug is not expected to be a controlled substance, since etifoxine is not a controlled substance in France or any other country in which it is sold. Currently, there is no clinically competitive anxiolytic drug on the market or in late stage development.
“I am pleased to inform you that the first dose to the first subject of our etifoxine PK/PD and safety study occurred this morning at 8 am Melbourne time,” said Dr. Massey in an email to stakeholders earlier this week.
“Everything has gone well so far. More soon!”