Itruvone (PH10) is an odorless investigational pherine nasal spray designed with a novel, rapid-onset potential mechanism of action (MOA) that is fundamentally differentiated from the MOA of all currently approved treatments for depression disorders. Itruvone, which is administered at microgram-level doses, is designed to engage and activate chemosensory neurons in the nasal cavity, which are connected to neural circuits in the brain that produce antidepressant effects. Specifically, itruvone’s proposed MOA involves the regulation of the olfactory-amygdala neural circuits believed to increase the activity of the limbic-hypothalamic sympathetic nervous system and increase the release of catecholamines. Importantly, unlike all currently approved oral antidepressants and rapid-onset ketamine-based therapy (KBT), including both intravenous ketamine and intranasal ketamine, Vistagen believes itruvone does not require systemic uptake and distribution of the compound to the brain to produce rapid-onset of antidepressant effects, avoiding side effects and safety concerns potentially associated with rapid-onset KBT and longer acting oral antidepressants.

In a small randomized, double-blind, placebo-controlled exploratory Phase 2A study of itruvone for in MDD conducted in Mexico City, at a 6.4μg dose, rapid-onset antidepressant effects were observed and sustained for an 8-week period (p=0.022).  In the itruvone 6.4μg treatment group, the HAM-D-17 score improved significantly from the baseline within one week and this effect was sustained until the Week 8 study endpoint. More information about the published itruvone Phase 2A study in MDD can be found in the peer-reviewed article, “A Placebo Controlled Trial of PH10: Test of a New Rapidly Acting Intranasally Administered Antidepressant,” published in the November-December 2019 edition of the British Journal of Pharmaceutical and Medical Research.

To confirm the favorable safety profile of itruvone established in three previous clinical studies conducted in Mexico, as well as facilitate Vistagen’s plans for Phase 2B development of itruvone in the U.S. as a fast-acting stand-alone treatment for MDD, a U.S. Phase 1 study was completed. There were no reported SAEs or discontinuations due to adverse events in the trial. Two AEs were reported during the treatment period, fatigue and headache, which occurred in the same subject. Both AEs resolved without sequelae and were mild in severity. Following itruvone administration, there were no clinically significant findings in ECGs, vital signs, and laboratory parameters. Overall, itruvone was well-tolerated and continued to demonstrate a favorable safety profile.

The FDA has granted Fast Track designation for itruvone as a potential treatment for MDD.

The completed successful U.S. Phase 1 study enables Vistagen’s plans for Phase 2B development of itruvone in the U.S. as a fast-acting stand-alone treatment for MDD.