Clinical Trials

NW-3509 is a voltage gated sodium channel (VGSC) inhibitor, originated from Newron’s Ion Channel program. It modulates neuronal hyper-excitability, and is active in a broad range of animal models of psychosis, mania, anxiety, cognition and depression. NW-3509 normalizes glutamate release induced by aberrant sodium channel activity.

The potential benefits of NW-3509 have been demonstrated in extensive animal models predictive of efficacy in psychiatric diseases, including models of psychosis and schizophrenia, such as amphetamine-induced hyperactivity, sensorimotor gating and information processing deficits (pre-pulse inhibition impairment induced by different stimuli), mania and depression. Efficacy of NW-3509 has also been demonstrated in models of aggression and compulsive behavior, as well as in short- and long-term memory tests. Sub-threshold doses of NW-3509 increased the activity of inactive doses of both typical and atypical antipsychotics in models of schizophrenia, psychosis and mania. Preclinical  data indicate that NW-3509 may add to or synergize with antipsychotic drugs to produce a combined therapeutic effect by modulating glutamate and dopamine systems that have been associated with schizophrenia symptoms.

 

* On January 15, 2015, Newron Pharmaceuticals, a research and development company focused on novel CNS and pain therapies, announced  the completion of the first in man US Phase I study of its novel sodium channel blocker NW-3509. The Phase I study performed in 54 healthy subjects in six independent cohorts (nine subjects each) who received single doses of NW-3509 ranging from 1-30 mg, or placebo (2:1), was overseen by an Independent Safety Monitoring Board who reviewed all safety, tolerability and plasma level data at each dose level prior to recommending administration of higher doses. NW-3509 was well-tolerated at all doses. At the maximum feasible dose of 30 mg, adverse events reported in the NW-3509 group (three subjects) included somnolence, headache, and orthostatic tachycardia, while one placebo subject complained of somnolence. In general, most events were transient, and were rated as mild in severity. No pattern of abnormal results was detected in vital signs, laboratory tests, or ECG results in NW-3509-treated subjects compared to placebo. Plasma concentrations of NW-3509 increased with higher doses; the mean Cmax at 20 mg and higher doses matched or exceeded the efficacious plasma concentrations in animal models of schizophrenia when NW-3509 was given as add-on therapy.
Newron plans to perform a double-blind, placebo-controlled randomized Phase II trial of NW-3509 as add-on treatment in schizophrenic patients on stable and adequate doses of atypical antipsychotics, whose symptoms are not effectively controlled by their medication. This 4-week study of the safety and preliminary evidence of efficacy of NW-3509 will be performed internationally and is expected to start in Q2 2015.

* On April 8, 2014, Newron Pharmaceuticals has announced that results from new mechanistic and behavioral studies with NW-3509 confirm its potential for use in patients with schizophrenia. These studies, together with preliminary results from a US Phase I study have been presented at the 4th Biennial Schizophrenia International Research Society (SIRS) Conference on Monday 7th April, 2014 in Florence, Italy. New mechanistic studies have confirmed NW-3509’s selectivity to block voltage gated sodium channels (VGSCs) based on the evaluation of over 130 targets including receptors, channels, transporters and enzymes. This blockade leads to the inhibition of excessive glutamate release that has not been addressed by current antipsychotics. These effects make NW-3509 unique and give it the potential to improve inadequate response when used in conjunction with marketed antipsychotics in patients with schizophrenia.
New behavioural studies with NW-3509, either alone or in combination with first or second generation antipsychotics, demonstrated significant activity in animal models (increased locomotion, aggression, pre-pulse inhibition, cognitive impairment) of schizophrenia independent of the stimulus (amphetamine, MK-801, PCP, scopolamine, sleep deprivation, natural impairment) used to produce the deficit. Benefits have also been demonstrated in animal models of mania, depression and obsessive/compulsive disorders.
Results from an ongoing Phase I trial in healthy volunteers in the US have indicated that NW-3509 at the doses administered is well tolerated, and exposure increases with increasing dose. Exposure in humans measured at the current doses overlap with exposure demonstrated at doses associated with significant benefit in animal models.

* On March 28, 2014, Newron Pharmaceuticals has announced that results from new mechanistic and behavioral studies with NW-3509 confirm its potential for use in patients with schizophrenia. These studies, together with preliminary results from a US Phase I study will be presented at the 4th Biennial Schizophrenia International Research Society (SIRS)

The first Phase I trial in healthy volunteers, performed in the US is nearing completion. Preliminary data will be presented at the SIRS conference.

* On August 10, 2011, Newron Pharmaceuticals announced it has received approval to start its first in-man trial in the US. The investigational new drug (IND) application for NW-3509 was filed on July 5, 2011. NW-3509 is the first selective, voltage gated sodium channel (VGSC) modulator, being specifically developed as an add-on therapy for schizophrenia.

* On July 13, 2011, Newron Pharmaceuticals has announced that it has submitted to the FDA an investigational new drug (IND) application for NW-3509, the first selective, voltage gated sodium channel (VGSC) modulator, being specifically developed for schizophrenia therapy. 

The application is seeking FDA approval to conduct a first human dosing trial in non-patient volunteers. The IND submission follows prior meetings with the FDA and MHRA (UK) and incorporates their suggestions and recommendations. NW-3509 has demonstrated activity in numerous models that mimic psychotic disorders, especially schizophrenia, both as monotherapy and as add-on treatment to currently available anti-psychotics. It significantly reduces abnormalities in pre-pulse inhibition (PPI), a measure of information processing and cognition, that has shown to be abnormal in patients with schizophrenia. The addition of NW-3509 to the treatment regimen of patients who are not benefitting adequately from their current medication, has the potential to result in clinical benefits and to allow the use of lower dose anti-psychotic treatments, thus significantly reducing dose-dependent side effects.