Newron Reports New Data on Evenamide Efficacy in Schizophrenia Study

Newron Pharmaceuticals S.p.A. (Newron), a biopharmaceutical company based in Milan, has released new findings from the international, randomized, double-blind, placebo-controlled study 008A. This study assessed the efficacy and safety of evenamide (30 mg bid) as an add-on treatment for 291 patients who were not responding to their current second-generation antipsychotic medications, including clozapine. Previously, top-line results announced on April 30, 2024, indicated that the study had achieved its primary endpoint of improving the Positive and Negative Syndrome Scale (PANSS) Total Score, as well as a key secondary endpoint, an improvement of the Clinical Global Impression of Severity (CGI-S).

Further analysis revealed that evenamide had significant effects on several secondary endpoints by Day 29:

- PANSS Total Score: A substantial proportion of patients exhibited a clinically relevant improvement (over 20% from baseline) with a p-value of less than 0.05.
- CGI-C Ratings: The mean rating at the endpoint was 3.3 for evenamide compared to 3.5 for placebo, with a p-value of less than 0.001. Additionally, a higher proportion of patients showed any improvement and were rated as at least "much improved," with 31.3% for evenamide versus 17.3% for placebo; p-value = 0.006.
- PANSS Positive and Negative Subscales: Both demonstrated a significant mean change from baseline with p-values of less than 0.05.

Sensitivity analyses further confirmed statistically significant improvements in the primary and secondary endpoints for evenamide, regardless of the population analyzed or the statistical methods used. Examples include:

- PANSS Total (WOCF ANCOVA): p-value = 0.008.
- PANSS Total (Multiple Imputation ANCOVA): p-value = 0.006.
- CGI-S (Multiple Imputation ANCOVA): p-value = 0.014.

The addition of evenamide to the existing antipsychotic regimen was well tolerated by patients, showing no significant increases in extrapyramidal symptoms, weight gain, blood glucose levels, metabolic syndrome, sexual dysfunction, CNS, or cardiac effects, nor laboratory abnormalities.

Study 008A is pivotal as it is the first well-designed study to demonstrate the efficacy of an adjunctive treatment in patients who do not respond to existing antipsychotic medications. Evenamide is also noteworthy for being the first glutamate modulator to show efficacy in inadequately responding patients with schizophrenia in a placebo-controlled study.

Dr. Ravi Anand, Chief Medical Officer of Newron, emphasized the clinical relevance of these new efficacy results. The findings show a significant proportion of evenamide patients were rated as "much improved" based on CGI-C ratings that consider not only psychosis symptoms but also the impact on social interactions, insight, and functioning. Improvements were seen in both positive and negative symptoms of schizophrenia, and the benefits of the treatment increased up to Day 29, suggesting larger and longer-lasting effects with extended treatment.

Evenamide is an orally available new chemical entity that blocks voltage-gated sodium channels (VGSCs) and does not affect over 130 other CNS targets. By inhibiting VGSCs, it normalizes glutamate release without affecting basal glutamate levels. Animal models of psychosis have shown that combinations of ineffective doses of evenamide and other antipsychotics, including clozapine, have provided benefits, hinting at potential synergies in their mechanisms of action.

Newron Pharmaceuticals continues to focus on developing innovative therapies for diseases of the central and peripheral nervous system. Evenamide promises to be a potential first add-on therapy for patients with symptoms of schizophrenia who do not respond adequately to current treatments.

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