Newron announces results of Phase I study of NW-3509, Phase II study in schizophrenia patients planned for Q2 2015
Newron Pharmaceuticals S.p.A., a research and development company focused on novel CNS and pain therapies, has announced the completion of the first in man US Phase I study of its novel sodium channel blocker NW-3509. This new chemical entity (NCE) is a product of Newron’s in-house ion-channel discovery program that also identified safinamide, a unique dual mechanism treatment that was recommended for approval by the CHMP in December 2014 as an add-on treatment for Parkinson’s disease (PD), and has been submitted for the same indication in the US.
NW-3509 is an orally available NCE that specifically targets voltage-gated sodium channels. It modulates sustained repetitive firing, without inducing impairment of normal neuronal excitability. NW-3509 normalizes glutamate release induced by aberrant sodium channel activity.
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.
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.
Ravi Anand, Newron’s CMO, stated: “NW-3509 may improve efficacy of current antipsychotics, allowing a reduction of their dosage, and of associated side effects e.g., metabolic syndrome, tardive dyskinesia, extra-pyramidal side effects (EPS). Moreover, given its neuronal stabilization properties, NW-3509 may reduce relapses and prevent or treat episodes of psychosis due to established super-sensitivity psychosis (SSP) induced by antipsychotics. It may also benefit domains of symptoms such as cognition, mood disorders and suicidality that are currently not managed effectively by available treatments.”
Source: Newron Pharmaceuticals