Newron Pharmaceuticals, a biopharmaceutical company focused on the development of novel therapies for patients with diseases of the central and peripheral nervous system (CNS), today announced positive top-line results from its potentially pivotal study 008A, evaluating the safety, tolerability and efficacy of evenamide (30 mg bid) in patients with chronic schizophrenia currently being treated with a second-generation antipsychotic including clozapine, but demonstrating an inadequate response to that treatment.
The study met its primary endpoint of improvement on the Positive and Negative Syndrome Scale (PANSS) Total Score as well as the key secondary endpoint of improvement of the Clinical Global Impression of Severity (CGI-S).
Study 008A was a four-week, international, randomized, double-blind and placebo-controlled add-on Phase II/III study performed in 45 centers in 11 countries in Europe, Asia and Latin America. 291 patients were randomized to treatment either with evenamide or placebo as add-on to their current antipsychotic therapy.
Evenamide confirmed its favourable safety and tolerability profile, with a high rate of completion. Two hundred and eighty of the 291 patients completed the study with only three patients discontinuing the study due to adverse events, two of them on evenamide and one patient on placebo who died during the study. No new or specific concerns were raised in the study; only 25% of the patients in the study experienced at least one adverse event (evenamide 25% versus placebo 25.8%). There was no difference in the incidence of CNS, psychiatric, gastrointestinal or other adverse events between evenamide and placebo. The most common adverse events reported in patients treated with evenamide were headache, vomiting and nasopharyngitis (three patients, each); similar numbers of patients on placebo experienced these adverse events.
In the study, the addition of 30 mg (bid) of evenamide to the patients’ current antipsychotic medication was associated with a highly statistically significant (p-value 0.006) reduction in the PANSS Total Score of 10.2 points, compared to 7.6 points in patients treated with placebo at day 29; the least square mean difference (LS mean difference) was 2.5.
For the key secondary measure, the Clinical Global Impression of Severity (CGI-S), the LS mean difference between patients treated with evenamide and placebo was 0.16; the corresponding p-value was 0.037.
Ravi Anand, MD, Chief Medical Officer of Newron, stated: “The results seen in study 008A with evenamide are ground-breaking and unique from many perspectives. This is the first major international study to demonstrate the significant benefit of adding a new chemical entity (NCE) to poorly responding, compliant schizophrenia patients being treated with a second-generation antipsychotic. It is also the first demonstration of efficacy in a placebo-controlled trial of a NCE acting exclusively through glutamatergic inhibition. These results, together with the recently reported one-year efficacy results in treatment-resistant patients, substantiate the pivotal role of glutamate in finding new therapeutic options for schizophrenia patients.”
Additional details from the study will be disclosed in the coming weeks.
