Evenamide: New Positive Results From Study 008A

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Newron Pharmaceuticals shared new positive top-line results from study 008A—which evaluated the safety, tolerability, and efficacy of twice daily evenamide 30 mg in patients with chronic schizophrenia currently treated with a second-generation antipsychotic including clozapine who have demonstrated an inadequate response to said treatment.¹

"I’m very excited that, for the first time ever, a drug that acts purely on a glutamatergic mechanism of action has shown treatment efficacy in schizophrenia. These are study results that we could have only dreamed about a few months ago," Ravi Anand, MD, Chief Medical Officer of Newron, exclusively told Psychiatric Times.

Study 008A was a 4-week, international, randomized, double-blind, and placebo-controlled add-on phase 2/3 study performed in 45 centers in 11 countries across Europe, Asia, and Latin America. Investigators randomized 291 patients to receive either evenamide or placebo as a concurrent treatment to their antipsychotic. The study met its primary endpoint of improvement on the Positive and Negative Syndrome Scale (PANSS) Total Score and the key secondary endpoint of improvement of the Clinical Global Impression of Severity (CGI-S). The addition of twice daily 30 mg of evenamide to the patients’ current antipsychotic medication was associated with a highly statistically significant (P = 0.006) reduction in the PANSS Total Score of 10.2 points, compared with 7.6 points in patients treated with placebo at day 29; the least square mean difference (LS mean difference) was 2.5. As to the key secondary measure, the LS mean difference between patients treated with evenamide and placebo was 0.16 on the CGI-S (P = 0.037).

Investigators also confirmed evenamide’s favorable safety and tolerability profile. Approximately 280 of the 291 patients completed the study. Only 3 patients discontinued the study due to adverse events, 2 of them on evenamide and 1 on placebo who died during the study. Furthermore, only 25% of the patients in the study experienced at least 1 adverse event (evenamide 25% versus placebo 25.8%), and there was no difference in the incidence of CNS, psychiatric, gastrointestinal, or other adverse events between evenamide and placebo. The most common adverse events associated with evenamide treatment were headache, vomiting, and nasopharyngitis (3 patients, each). Similar numbers of patients on placebo experienced these adverse events. No new or specific concerns were raised in the study.

“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,” said Anand in the press release. “These results, together with the recently reported 1-year efficacy results in treatment-resistant patients, substantiate the pivotal role of glutamate in finding new therapeutic options for schizophrenia patients.”

This research builds upon previous successes with evenamide treatment. In January 2024, Newron shared data from a 1-year open label study evaluating evenamide as an add-on to antipsychotics for the management of treatment-resistant schizophrenia (TRS), which also demonstrated positive results. Evenamide showed sustained benefit that increased throughout the 1-year course of treatment, and more than 70% of the patients experienced clinically significant reduction in disease severity.² In August 2023, Newron shared a report with highlights from the first half of 2023 in its exploration of evenamide as a treatment for TRS. Study 014/015—the first international trial of an antipsychotic new chemical entity as an add-on therapy to a single antipsychotic in patients with TRS—showed that evenamide was safe and well-tolerated among participants at all doses. There was very low incident of treatment-emergent adverse events.³

Newron plans to share additional details from study 008A soon.

References

1. Newron announces positive top-line results from potentially pivotal phase II/III study 008A with evenamide in schizophrenia patients. News release. April 30, 2024. https://www.newron.com/news-and-media/regulatory-news/newron-announces-positive-top-line-results-potentially-pivotal-phase

2. Kuntz L. Evenamide: new results show 70% of patients saw reduction in treatment-resistant schizophrenia severity. Psychiatric Times. January 4, 2024. https://www.psychiatrictimes.com/view/evenamide-new-results-show-70-of-patients-saw-reduction-treatment-resistant-schizophrenia-severity

3. O’Brien E. Research on evenamide as a treatment for TRS reviewed in highlights from first half of 2023. Psychiatric Times. August 23, 2023. https://www.psychiatrictimes.com/view/research-on-evenamide-as-a-treatment-for-trs-reviewed-in-highlights-from-first-half-of-2023