Naurex’s lead compound, GLYX-13, is a novel and selective NMDAR partial agonist in development as an adjunctive therapy for patients with depression who do not respond adequately to current therapy.
In preclinical studies, GLYX-13 exhibited promising efficacy signatures, but without any sign of serious side effects at doses up to 50-100 times greater than the expected therapeutic dose—an unprecedented result for drugs targeting the NMDA receptor, providing the widest therapeutic window among known NMDAR modulators. The good safety profile of GLYX-13 was confirmed in a Phase I clinical trial.
In December 2012, Naurex presented the results of its first Phase II trial of GLYX-13 at a major medical meeting. The trial evaluated the effects of a single dose of GLYX-13 in subjects with major depressive disorder who were not achieving adequate responses to their current antidepressant regimens. The trial results are summarized below:
- Safety: GLYX-13 was well-tolerated overall. Reported side effects were mild to moderate and consistent with those observed in subjects receiving placebo.
- No psychotomimetic side effects: Importantly, and consistent with previous studies, subjects receiving GLYX-13 did not experience any of the psychotomimetic (psychosis-like) effects that are induced with other NMDAR agents such as ketamine.
- Rapid onset of antidepressant effect: Subjects receiving GLYX-13 had a statistically significant reduction in depression scores within 24 hours following a single administration.
- Long duration of antidepressant effect: The statistically significant reduction in depression scores persisted for an average of 7 days following a single administration of GLYX-13.
- Robust effect size: The effect size, a measure of antidepressant efficacy, observed with GLYX-13 at 24 hours and 7 days after a single administration, was nearly double the effect size seen with most SSRI antidepressant agents after 4-6 weeks of repeated dosing.
These findings suggest GLYX-13's potential as a breakthrough therapy in depression—a disorder that is currently treated with agents characterized by delayed onset of effect, significant limiting side effects, and mediocre efficacy, leaving as many as 50% of patients without adequate relief.
Naurex is now conducting a second Phase II clinical trial (C-202) evaluating repeated dosing of GLYX-13 in subjects with depression who are experiencing inadequate response to their current antidepressant agents. Initial results from this trial are expected in late 2013. To learn more about the C-202 Phase II trial, visit the listing at www.ClinicalTrials.gov.
Naurex has previously reported results from an initial Phase II clinical trial (C-201) of GLYX-13, as noted in the preceding section. Trial C-201 was a randomized, double-blind, placebo-controlled study of the efficacy and safety of intravenous GLYX-13 in subjects with major depressive disorder who had demonstrated inadequate or partial response to other antidepressants. It was conducted at 12 clinical centers in the U.S. Outcome measures included ratings of signs, symptoms and changes in depression scores on standard rating scales for mood and psychiatric disorders. Safety was also assessed.
Naurex has also previously reported results from a Phase I safety trial of GLYX-13, which showed that adverse events for the groups receiving GLYX-13 and placebo were all rated as mild, and there were no signs of the schizophrenia-like side effects associated with other drugs that modulate the NMDA receptor.
The Phase I trial was a randomized, double-blind, placebo-controlled single ascending dose level study of the safety, tolerability and pharmacokinetics of various dose levels and formulations of GLYX-13 in healthy volunteers. The primary outcome measures included observational and laboratory-confirmed safety parameters, including schizophrenia-like side effects. None were observed, even following administration of single doses of GLYX-13 that were significantly higher than the expected therapeutic dose based on data from animal studies. The pharmacokinetics of GLYX-13 demonstrated drug exposure in humans that correlated to exposure in animals at the same doses.