PHOENIX, Dec. 10, 2014 /PRNewswire/ — Naurex Inc. today announced that Phase 2b data presented at the Annual Meeting of the American College of Neuropsychopharmacology demonstrated that repeat-dose adjunctive treatment along with GLYX-13, a novel NMDA receptor modulator, resulted in robust and sustained antidepressant effects in subjects along with inadequate responses to their current antidepressants. GLYX-13 was well-tolerated along with no drug-related serious edge events reported, including no sign of the psychotomimetic, or psychosis-like, effects associated along with NMDA receptor antagonists such as ketamine. These Brand-new data confirm the efficacy and safety results from an earlier Phase 2 single-dose study of GLYX-13, which likewise documented the drug’s rapid onset of antidepressant activity in as little as two hours.
Unlike most currently approved antidepressants, which act on serotonin and related neurotransmitter pathways in the brain, GLYX-13 works through an entirely different mechanism, mobilizing glutamate pathways to improve neuronal plasticity and improve the communication between neuronal cells. Dysfunction in these activities is increasingly recognized by scientists as an crucial contributor to depression and others serious disorders of the central nervous system (CNS).
“Currently marketed antidepressants all job via similar pathways in the brain and do not adequately treat 45 percent of people along with major depression. This presents a huge problem,” said Sheldon Preskorn, M.D., a study investigator and professor of psychiatry at the University of Kansas School of Medicine-Wichita. “However, there are now several studies showing that lots of of these patients respond to investigational antidepressants, such as GLYX-13, that appear to job via a different mechanism, the NMDA receptor. These Phase 2b data are especially encouraging since repeated treatments along with GLYX-13 make a sustained response in patients that inadequately respond to marketed antidepressants. These results are of excellent clinical importance.”
Norbert Riedel, Ph.D., president and chief executive officer of Naurex, commented, “The inadequacies of existing therapies have actually increased interest in the antidepressant properties of NMDA receptor antagonists adore ketamine, however the serious adverse effects of these drugs limit their practical utility. After evaluating GLYX-13 in over 500 subjects to date, we believe our novel mechanism has actually achieved the right balance in selectively modulating the NMDA receptor to achieve the speed and efficacy of the NMDA receptor antagonists, however devoid of the adverse effects.”
Dr. Riedel continued, “We have actually discussed the wealth of GLYX-13 data along with the FDA and have actually a clear understanding of the Phase 3 trial design called for to file a Brand-new Drug Application and ultimately offer this potentially crucial Brand-new therapy to the millions of patients that are poorly served by current treatments.”
GLYX-13 Phase 2b Study Design
The GLYX-13 Phase 2b study was divided in to three parts: a six-week adaptive-dose treatment stabilization period, followed by a six-week randomized withdrawal period and a four-week wash-out period. The study was made to evaluate safety and efficacy along with repeat dosing and to find out optimal dose (5 mg/kg or 10 mg/kg) and dose intervals (weekly or bi-weekly). Subjects were evaluated for modifications in depressive symptoms on a weekly basis by off-site independent raters using the HDRS-17 scale. Both subjects and evaluators were blind to the study design.
All 386 subjects were dosed along with an intravenous bolus injection of GLYX-13 at the start of the treatment stabilization period. Subjects received weekly injections of drug until a response was established (reduction in HDRS-17 to a score much less compared to or equal to 50 percent of pre-dose baseline). Upon achieving response, subjects were then dosed along with weekly intravenous injections of placebo to force a relapse in depressive symptoms (boost in HDRS-17 to a score better compared to 50 percent of pre-dose baseline). Upon relapse, subjects were again dosed along with GLYX-13 to evaluate whether efficacy could be reestablished. This cycle was repeated along with weekly doses of either GLYX-13 or placebo for 6 weeks. On average, subjects received four injections of GLYX-13 and two injections of placebo throughout this period. This forced relapse component of the design allowed for evaluation of optimal dose interval, the ability of GLYX-13 to reestablish efficacy if the drug were discontinued, and the antidepressant effects of both drug and placebo in each subject.
Subjects that did not respond throughout the stabilization period were excluded prior to the randomized withdrawal period. throughout this six-week withdrawal period, subjects were randomized to keep on receiving GLYX-13 or to have actually the drug withdrawn and replaced along with placebo. throughout the following four-week washout period, all subjects received injections of placebo.
HDRS-17 is a usually used instrument that monitors modifications in subjects’ responses on a number of depressive symptoms such as depressed mode, insomnia, somatic symptoms and difficulty in day-to-day job and activities. The HDRS-17 depression assessment scale was administered to subjects by off-site independent raters.
GLYX-13 Demonstrates Ability to Induce and Reestablish Antidepressant Effect
Overall, GLYX-13 was substantially a lot more effective compared to placebo in alleviating symptoms of depression, it was able to again alleviate symptoms after a forced relapse, and its efficacy in reducing symptoms of depression increased over the course of the treatment period.
Responders demonstrated a considerable difference between responses to drug versus placebo throughout the treatment stabilization period, showing an standard 2.8 point decrease in HDRS-17 scores (improvement of depressive symptoms) in the week after receiving GLYX-13 and an standard 3.1 point increase in HDRS-17 scores (worsening of depressive symptoms) in the week after receiving placebo (p-value = 0.03).
During the treatment stabilization period, reductions in depression scores were compounded incrementally along with each dose of GLYX-13. For subjects responding to GLYX-13, the very first dose of GLYX-13 resulted in an standard reduction in HDRS-17 scores of 4.9 points from baseline; this effect increased to a cumulative standard reduction in HDRS-17 scores of 12.5 points from baseline by the end of the six-week stabilization period.
GLYX-13 Was Well-Tolerated along with Durable Antidepressant Effects
GLYX-13 was found to be well-tolerated throughout the study, along with no drug-related serious edge events and no subjects discontinuing treatment because of drug-related edge events.
A previous Phase 2a study demonstrated that the antidepressant effects of GLYX-13 lasted for an standard of seven days after a single dose; the Phase 2b study data demonstrated that this durable effect continues to build along with repeat doses. Subjects treated along with GLYX-13 throughout the very first six-week treatment stabilization period, then randomized to receive placebo injections, continued to prove to effects of the GLYX-13 treatment throughout the following six-week withdrawal period and the subsequent four-week washout period – never returning toward the baseline HDRS-17 score over the entire post-treatment period. Durability of effect was likewise seen in the subjects that were randomized to keep on GLYX-13 treatment throughout the withdrawal period.
Previous Phase 2a Study Established Rapid Onset of Action
In the Phase 2a study, a considerable reduction in depressive symptoms was seen in as little as two hours following a single injection of GLYX-13 in subjects that had failed treatment along with one or a lot more antidepressant agents. The effect persisted for an standard of seven days. The effect size, a measure of the magnitude of the drug’s antidepressant efficacy, observed at 24 hours and at seven days after a single administration of GLYX-13, was nearly double the effect size seen along with most others antidepressant drugs after four to 6 weeks of repeated dosing.
GLYX-13 to Advance to Phase 3 in 2015
Naurex has actually completed an end-of-Phase 2 meeting along with FDA and is proceeding along with its Phase 3 program, expected to start in 2015.
Naurex recently completed an $80 million Collection C financing to keep on development of GLYX-13 and its next-generation, orally available NMDA receptor modulator NRX-1074, which is completing a Phase 2 study in major depressive disorder. The financing will certainly likewise support advancement of the company’s preclinical NMDA receptor modulators for others CNS indications.
Naurex’s proprietary drug discovery platform is based on the pioneering job of company founder Joseph Moskal, Ph.D. and his colleagues at the Falk Focus for Molecular Therapeutics at Northwestern University. Naurex retains exclusive global development and commercialization rights for the discovery platform and all resulting molecules.
About Naurex Inc.
Naurex is a clinical stage biopharmaceutical company producing transformative therapies for challenging disorders of the central nervous system. The company has actually built a platform for discovering drugs that improve synaptic plasticity, or strengthen the network for neural cell communication. Molecules discovered by Naurex achieve this through a novel mechanism that modulates the NMDA receptor – very compared to shutting it down – resulting in drugs that are both highly effective and well tolerated. Naurex’s lead molecule, GLYX-13, has actually demonstrated rapid, robust, and sustained efficacy in multiple Phase 2 clinical studies in depression, an area of higher unmet requirement that has actually seen little innovation in decades. NRX-1074, a next-generation, orally bioavailable drug candidate, is in Phase 2 clinical development in depression. Naurex’s platform has actually yielded a rich pipeline of subtype-selective NMDA receptor modulators along with the potential to treat a broad set of psychiatric and neurologic disorders.
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SOURCE Naurex Inc.