Evenamide Phase II/III Study 008A Shows Promising Results in Schizophrenia

Newron Pharmaceuticals, a biopharmaceutical firm dedicated to pioneering treatments for central and peripheral nervous system disorders, has reported encouraging findings from its Phase II/III clinical trial, study 008A. The trial assessed the safety, tolerability, and efficacy of evenamide, a novel compound, in chronic schizophrenia patients who have not responded adequately to second-generation antipsychotics, including clozapine.

Conducted over four weeks across 45 centers in 11 countries, the randomized, double-blind, placebo-controlled study involved 291 participants. These individuals were assigned to receive either evenamide or a placebo in addition to their ongoing antipsychotic treatment. The trial successfully achieved its primary goal, which was to demonstrate an improvement in the Positive and Negative Syndrome Scale (PANSS) Total Score, as well as a significant improvement in the Clinical Global Impression of Severity (CGI-S), a key secondary outcome measure.

Evenamide demonstrated a positive safety profile and good tolerability, with a completion rate of nearly 97%. Only three participants withdrew due to adverse events, with two from the evenamide group and one from the placebo group, who unfortunately passed away. The study did not identify any new safety concerns, as adverse events were comparable between the evenamide group (25%) and the placebo group (25.8%). The most frequently reported adverse events in the evenamide group were headache, vomiting, and nasopharyngitis, each affecting three patients, with similar occurrences in the placebo group.

The study results showed that the addition of evenamide to the patients' existing antipsychotic regimen led to a statistically significant reduction in the PANSS Total Score by 10.2 points, as opposed to a 7.6-point reduction in the placebo group by day 29, with a least square mean difference of 2.5. For the CGI-S, the least square mean difference was 0.16, with a corresponding p-value of 0.037.

Dr. Ravi Anand, Newron's Chief Medical Officer, highlighted the groundbreaking nature of the study's results, emphasizing that it is the first international trial to show significant benefits from adding a new chemical entity (NCE) to the treatment of schizophrenia patients with poor responses to second-generation antipsychotics. The study also marks the first placebo-controlled trial to demonstrate the efficacy of an NCE that acts solely through glutamatergic inhibition. These findings, along with the one-year efficacy results in treatment-resistant patients, underscore the critical role of glutamate in developing new treatment options for schizophrenia.

Further details of the study are set to be released in the coming weeks, with a conference call scheduled for the same day at 3:00 PM CET to discuss the results. Evenamide, an orally available NCE, selectively targets voltage-gated sodium channels (VGSCs) and corrects the abnormal glutamate release caused by these channels without impacting the baseline levels of glutamate. This mechanism of action suggests potential synergies with current antipsychotics, offering hope for patients who have not responded well to existing treatments.

Newron Pharmaceuticals, headquartered in Italy, is also known for developing Xadago®/safinamide, which has been authorized for marketing in several regions globally for the treatment of Parkinson’s disease. The company continues to explore evenamide's potential as an innovative add-on therapy for schizophrenia, furthering its commitment to advancing CNS treatment options.