Early Beginnings
The original, non-deuterated drug (etifoxine) was originally developed to compete with tranquilizing and sedative BZs of the 1960’s, such as Valium and Librium. But it was mischaracterized as a mild benzodiazepine, because of its lack of typical benzodiazepine side effects, like sedation and ataxia. Hoechst sold the rights to the drug, without knowing its true efficacy and unaware of its mechanism of action. A small pharmaceutical distributor has been producing and distributing the drug off-patent since 1979, in limited markets. The drug was never developed in the U.S. or broader European markets.
Discovering the Extraordinary Mechanism of Action
Contrary to what was originally believed, French researchers in the 2000’s discovered that etifoxine did not interact at the benzodiazepine site on GABA receptors! It took sophisticated modern research techniques to reveal a truly significant discovery: The drug increases the levels of natural neurosteroids, like allopregnanolone (ALLO), a highly potent and effective modulator of GABA channels, and that the clinically observed effects could be reversed in pre-clinical experiments by blocking the natural synthesis of these steroids. Scientists quickly took notice of this unique biological action and began to explore etifoxine in models of other indications where neurosteroids (like ALLO) had shown efficacy: Alzheimer’s Disease, Multiple Sclerosis, Parkinson’s Disease and traumatic brain injury, to name a few.
Etifoxine – No Patent Protection – Not Viable
The stage was set for an old drug to be rejuvenated, but the original patents had expired and most of the therapeutic indications had already been disclosed (or patented). Without patent protection, there was no business rationale to re-develop the drug in any new markets, which explains why etifoxine was never introduced into the United States. This is the rationale behind the discovery and development of GRX-917: a vastly improved variant of etifoxine, with patent protection.