Today, atai Life Sciences N.V. (Nasdaq: ATAI) a clinical-stage biopharmaceutical company aiming to transform the treatment of mental health disorders, and its subsidiary GABA Therapeutics, announced final positive results from a Phase 1 clinical trial of GRX-917 that were previously announced as preliminary results during atai’s R&D day. The randomized, double-blind, placebo-controlled trial was designed to evaluate the safety, tolerability, and pharmacokinetic profile of single and multiple ascending doses of orally administered GRX-917.
Overall, compared to placebo, GRX-917 was well-tolerated and neither dose-related nor dose-limiting adverse events were observed. There were no serious adverse events reported nor discontinuations due to drug administration. Furthermore, in contrast to current first-line anxiety disorder treatments such as benzodiazepines, sedation was found to be comparable to placebo.
Dose-dependent increases in qEEG beta power, a biomarker for GABA receptor activation, was demonstrated in subjects who received GRX-917 but not with those who received a placebo, providing evidence of target engagement consistent with GRX-917’s putative mechanism of action.
GRX-917 is a deuterated version of etifoxine, which is an anxiolytic approved in France, with rapid onset and efficacy comparable to leading benzodiazepines like alprazolam and lorazepam that are currently considered the standard of care but is non-addictive with minimal side effects. Etifoxine is thought to achieve its anxiolytic activity by increasing endogenous production of brain neurosteroids like allopregnanolone. Dysregulation of neurosteroidogenesis has been implicated in a broad range of neuropsychiatric diseases including generalized anxiety disorder (GAD), anxious depression, social anxiety disorder (SAD), panic disorder, and postpartum depression.
Florian Brand, CEO of atai
“According to a World Health Organization report, the number of people living with anxiety disorders globally grew from 298 million people in 2020 to 374 million in 2021. Given the catastrophic effects of the pandemic on the mental health of people around the world, the need for a better tolerated, safer therapeutic for GAD and other anxiety disorders has never been more pronounced.”
“We are very encouraged by the Phase 1 results for GRX-917,” said Mario Saltarelli, MD, PhD, CEO and CMO of GABA. “Based on etifoxine’s safety and efficacy profile, we believe GRX-917 will offer a differentiated treatment for GAD with fewer side effects—such as sedation, respiratory depression, and withdrawal.”
In the single-ascending dose (SAD) portion of the trial, adverse events were observed in 53% (17/32) of GRX-917 treated subjects, comparable to 50% (5/10) observed in placebo-treated subjects. Adverse events related to GRX-917 specifically occurred in 25% (8/32) of subjects and were all mild in severity.
In the multiple-ascending dose (MAD) portion of the trial, adverse events were observed in 60.5% (26/43) of GRX-917 treated subjects, also comparable to 60% (9/15) observed in placebo-treated subjects. Adverse events related to GRX-917 specifically occurred in 32.6% (14/43) of subjects and were all mild in severity. The results of these two trial phases indicate that there were no dose-limiting adverse events in trial subjects at higher dosages and no benzodiazepine-like side effects, including sedation were observed.
Biomarker/Pharmacodynamic (PD) Data
Dose- and exposure-dependent increases in beta power were observed by quantitative electroencephalogram (qEEG) in healthy volunteers receiving single doses of GRX-917 but not in those who received a placebo. These results show that GRX-917 has measurable effects on the central nervous system and provide evidence of GABA receptor target engagement and mechanism of action.
About atai Life Sciences
atai Life Sciences is a clinical-stage biopharmaceutical company aiming to transform the treatment of mental health disorders. Founded in 2018 as a response to the significant unmet need and lack of innovation in the mental health treatment landscape, atai is dedicated to acquiring, incubating, and efficiently developing innovative therapeutics to treat depression, anxiety, addiction, and other mental health disorders.
By pooling resources and best practices, atai aims to responsibly accelerate the development of new medicines across its companies to achieve clinically meaningful and sustained behavioral change in mental health patients.
atai’s vision is to heal mental health disorders so that everyone, everywhere can live a more fulfilled life.