Date: 2017-03-25
Type of
information: Presentation of results at a congress
phase: 2
Announcement: presentation of results at the 16th International Congress on Schizophrenia Research
Company: Newron Pharmaceuticals (Italy)
Product: evenamide (NW-3509)
Action
mechanism: antipsychotic/sodium channel blocker. Evenamide (NW-3509) is a new generation antipsychotic that acts through pathways that are not targeted by current treatments or other putative antipsychotics. It is associated with a functional blockade of voltage-gated sodium channels that inhibits glutamate release by reducing the firing rate of hyper-excited neurons and may normalize aberrant cortical and hippocampal activity.
Evenamide is an orally available new chemical entity that specifically targets voltage-gated sodium channels. The compound modulates sustained repetitive firing, without inducing impairment of normal neuronal excitability. Evenamide normalizes glutamate release induced by aberrant sodium channel activity. The potential benefits of the compound have been demonstrated in numerous preclinical models predictive of efficacy in psychiatric diseases, including models of psychosis such as amphetamine-induced hyperactivity, sensorimotor gating and information processing deficits (pre-pulse inhibition impairment induced by different stimuli), mania and depression. Efficacy of Evenamide 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 the compound increased the activity of inactive doses of both typical and atypical antipsychotics in models of schizophrenia, psychosis and mania. Moreover, given its neuronal stabilization properties, Evenamide may reduce relapses and prevent or treat episodes of psychosis due to established super-sensitivity psychosis (SSP) induced by antipsychotics. As it is devoid of the risk of drug-induced movement disorders or weight gain, Evenamide can be given in combination for extended periods of time.
Disease: schizophrenia
Therapeutic
area: CNS diseases - Mental diseases
Country: India, USA
Trial
details:
- The four-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 Positive and Negative Syndrome Scale (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 study protocol, including doses and study design, was finalized with FDA input and guidance, and received approval from the Drug Controller General of India (DCGI), as well as the institutional review board (IRB) at each center.
Latest
news:
- • On March 25, 2017, Newron Pharmaceuticals presented detailed results of a Phase IIa study with evenamide (NW-3509), in patients with schizophrenia. The results were presented at the 16th International Congress on Schizophrenia Research in San Diego. Results 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 [?5.1 (9.67)] than for placebo [-3.7 (9.65)]. For the PANSS Positive Symptoms sub-scale, a statistically significant/near significant improvement from baseline (mean baseline score: 14.8 ± 2.8) to Day 28 for Evenamide, compared to placebo [LS mean difference (SE)], was noted in the ANCOVA-LOCF [?1.28 (0.632), p=0.046], ANCOVA-OC [-1.48 (0.641), p=0.024], and MMRM [-1.19 (0.643), p=0.068] analyses.
- Numerically greater improvement with evenamide was also observed for patients’ functioning, assessed by the Strauss-Carpenter Level of Functioning scale, and severity of illness (Clinical Global Impression of Severity), compared to their standard antipsychotic alone. In addition, a global assessment of change from baseline in the patient’s overall condition (Clinical Global Impression of Change), performed by a clinician, showed a greater proportion of evenamide-treated patients rated as improved (54%), compared to placebo (36%).
- An additional analysis demonstrated that the proportion of patients who showed improvement on the PANSS Positive sub-scale at Day 28 was significantly greater (p=0.0043; Fisher’s exact chi-square test) for the evenamide group (74.5%) compared to the placebo group (43.6%).
- Evenamide in the range of 15-25 mg bid (30-50 mg/day) was well tolerated. The most frequent (>5% of patients in any group) adverse events (evenamide vs. placebo) were somnolence [8 (16.0%) vs. 5 (12.8%)], insomnia [5 (10.0% vs. 1 (2.6%)], overdose [3 (6.0%) vs. 1 (2.6%)], dry mouth [3 (6.0%) vs. 2 (5.1%)], headache [3 (6.0%) vs 0], and cold sweat/hyperhidrosis [2 (4.0%) vs. 0]. The incidence of ‘respiratory, thoracic and mediastinal disorders’ was higher for placebo [1 (2.0%) vs. 3 (7.7%)]. Most adverse events were of mild severity [Evenamide, 58 of 69 (84%); placebo, 30 of 34 (88%)]; 9 of 69 (13%) adverse events for evenamide and 4 of 34 (12%) for placebo were assessed as moderate.
- Two patients in the Evenamide group discontinued treatment due to adverse events: seizure (n=1) and atrial fibrillation (n=1). The proportions of patients with clinically notable abnormalities in vital signs or laboratory values were very low and were similar in the evenamide and placebo groups. The proportion of patients with clinically significant ECG abnormalities was low and similar between groups, and there was no evidence of effects on QTc. Assessment of extrapyramidal symptoms (EPS) using the Extrapyramidal Symptoms Rating Scale did not reveal any treatment-emergent EPS with evenamide treatment.
- • On January 3, 2017, Newron Pharmaceuticals announced preliminary results of a Phase IIa study with its sodium channel blocker, evenamide (NW-3509), in patients with schizophrenia. Detailed results will be presented at the 16th International Congress on Schizophrenia Research, 24-28 March 2017, in San Diego.
- The study was held in two U.S (n=61) and three Indian (n=28) study centers, and enrolled schizophrenia patients with a mean duration of illness of approximately 18 years and an average of 3 hospitalizations. 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, as well as functioning assessed by the Strauss-Carpenter Level of Functioning scale, compared to their standard antipsychotic. In addition, a global assessment of change from baseline in the patient’s overall condition (Clinical Global Impression of Change), performed by a clinician, showed a greater proportion of Evenamide-treated patients rated as improved (54%), compared to placebo (36%).
- • On April 5, 2016, Newron Pharmaceuticals announced that it presented at the 5th Biennial Schizophrenia International Research Society Conference the abstract “Evenamide (NW-3509), a Putative Antipsychotic, Targets Abnormal Electrical Activity and Glutamatergic Abnormalities in Improving Psychotic Symptoms in Patients with Schizophrenia in a Phase II, Placebo-controlled Trial”. A Phase II, placebo-controlled study in patients with schizophrenia experiencing breakthrough symptoms while on adequate doses of risperidone or aripiprazole is ongoing, in which evenamide is being evaluated at doses of 15-25 mg bid as add-on therapy for reducing positive symptoms and psychotic worsening.
Is
general: Yes
