Encouraging results of Phase IIa study with Evenamide in patients with schizophrenia

Unique mechanism: glutamate modulation and voltage-gated sodium channel blockade.

Newron Pharmaceuticals has presented detailed results of a Phase IIa study with its unique sodium channel blocker, Evenamide (NW-3509), in patients with schizophrenia. The new chemical entity is orally available and specifically targets voltage-gated sodium channels by a unique mechanism of action.

The results were presented at the 16th International Congress on Schizophrenia Research, 24-28 March 2017, in San Diego.

Ravi Anand, Newron’s Chief Medical Officer, stated: "Evenamide uniquely combines voltage-gated sodium channel blockade with attenuation of glutamate release. The results of this first study in patients with schizophrenia confirm preclinical data, which indicated that Evenamide might provide significant evidence of efficacy as an add-on to the most commonly prescribed atypical antipsychotics in patients with chronic schizophrenia, without effect on any of the over 130 neurotransmitters, enzymes, or transporters targeted by most antipsychotics."

Dr Anand continued: "The patients in this study, who were showing signs of worsening symptoms of psychosis while on doses of antipsychotics they had responded to in the recent past, benefited on all efficacy measures evaluated. The onset of improvement occurred early in treatment. Evenamide was not associated with any increase in extrapyramidal, sexual, endocrine, cardiac, laboratory or metabolic side effects caused by the use of antipsychotics. The addition of Evenamide to patients showing a worsening of their symptoms while on their current atypical antipsychotic was not only well-tolerated, but showed a consistent pattern of benefit on all efficacy measures assessed. These preliminary results warrant further investigation in larger and longer trials in patients with more severe symptoms."

The 4-week, Phase IIa, double-blind, placebo-controlled, randomized, multi-national study was designed to investigate the tolerability, safety and preliminary evidence of efficacy of Evenamide as an add-on treatment in 89 patients with a DSM-5 diagnosis of schizophrenia. Patients included in the study were primarily male (86%) and 19 to 60 years of age, with a mean baseline PANSS total score of 62.9 ± 7.4, and were experiencing break-through psychotic symptoms while on stable and adequate doses of risperidone (mean dose: 4.2 ± 2.0 mg/day; n=70) or aripiprazole (mean dose: 19.7 ± 7.0 mg/day; n=19), the atypical antipsychotics to which they had responded previously. The study was conducted in two U.S (n=61) and three Indian (n=28) study centers, and enrolled patients with schizophrenia with a mean duration of illness of approximately 18 years and an average of three hospitalizations. Patients were randomized to receive twice daily Evenamide (15-25 mg) or placebo, in addition to their current antipsychotic.

The results of the study indicate that patients treated with Evenamide showed improvement on the symptoms of schizophrenia assessed by the Positive and Negative Syndrome Scale (PANSS). The mean (SD) change from baseline at Day 28 for the PANSS total score was greater for Evenamide than for placebo.