Newron Pharmaceuticals S.p.A. (“Newron”), a biopharmaceutical company focused on the development of novel therapies for patients with diseases of the central nervous system (CNS) and pain, announced today preliminary 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.
Detailed results will be presented at the 16th International Congress on Schizophrenia Research, 24-28 March 2017, in San Diego.
Ravi Anand, M.D., Newron’s Chief Medical Officer, stated: “The results of this study are very encouraging. Evenamide was not associated with any dose-limiting toxicities, or the extrapyramidal, sexual, endocrine, and metabolic side effects associated with dopamine-blocking antipsychotics. The addition of Evenamide, which acts by attenuating glutamate release, 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 four-week, Phase IIa, double-blind, placebo-controlled randomized study was designed to investigate tolerability, safety and preliminary evidence of efficacy of Evenamide as an add-on treatment in 89 patients with schizophrenia. Patients included in the study 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 antipsychotic to which they had responded previously. 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. 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.
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%).
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 (AEs) (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%)], and headache [3 (6.0%) vs 0]. The incidence of AEs classified as ‘skin and subcutaneous disorders’ was higher in the Evenamide group [5 (10.0%) vs. 0], while the incidence of ‘respiratory, thoracic and mediastinal disorders’ was higher for placebo [1 (2.0%) vs. 3 (7.7%)]. Most AEs were of mild severity [Evenamide, 58 of 69 (84%); placebo, 30 of 34 (88%)]; 9 of 69 (13%) AEs for Evenamide and 4 of 34 (12%) for placebo were assessed as moderate.
Two patients in the Evenamide group discontinued treatment due to AEs: seizure (n=1) and atrial fibrillation (n=1). There was no evidence of any worsening of extrapyramidal symptoms, abnormal ECG findings, or clinically notable changes in laboratory values or vital signs (blood pressure, pulse or body weight) with Evenamide treatment, compared to placebo.