Newron Pharmaceuticals S.p.A. announced exciting topline results from Study 014, a phase II, international, randomized, open label, rater-blinded trial evaluating evenamide as an add-on to an antipsychotic (excluding clozapine) in patients with moderate to severe treatment-resistant schizophrenia (TRS) not responding to their current antipsychotic medication. While the primary objective of the study was safety and tolerability of the drug, efficacy over baseline was also assessed. Interim results from the first 100 patients at six weeks were previously reported in June 2022.

Notably, of the 161 patients who were randomized, 153 (95%) completed the six-week treatment period and 144 (94% of the completers) entered the extension study (Study 015). One patient discontinued treatment due to flu-like symptoms, and seven withdrew consent. Overall, the results from the complete study population are fully consistent with the findings from the first 100 patients at this timepoint.

The mean Positive and Negative Syndrome Scale (PANSS) total score, Clinical Global Impression of Severity (CGI-S) rating, and the Strauss-Carpenter Level of Functioning (LOF) total score significantly improved compared to baseline (p<0.001). The proportion of patients considered clinically important responders on the PANSS, the Clinical Global Impression of Change (CGI-C) and the CGI-S was in line with the proportion of the first 100 patients experiencing this level of benefit after six weeks. Mean improvement from baseline was also consistent for the Medication Satisfaction Questionnaire (MSQ) when compared to this measure for the first 100 patients.

The number of patients who experienced treatment-emergent adverse events (TEAEs) was low (26%) and none was rated severe; the most commonly reported TEAEs (=3%) were dizziness, pyrexia, and CPK increase. No treatment-emergent or clinically important findings for weight gain, metabolic syndrome, sexual dysfunction, neurological findings (based on ESRS-A and neurological examination), standard laboratory tests or electrocardiograms (ECGs) were reported. This adverse event profile was also similar to that seen from the first 100 patients.

Detailed results from study 014 will be presented at the 36th European College of Neuropsychopharmacology (ECNP) Congress, taking place 7-10 October 2023 in Barcelona, Spain. In addition, Newron will be presenting the results of the previously announced six-month endpoint from the first 100 patients at the 31st European Congress of Psychiatry taking place 25-28 March 2023, in Paris, France, and the one-year data at the Congress of the Schizophrenia International Research Society taking place 11-15 May 2023, in Toronto, Canada. Newron expects to initiate a potentially pivotal, multinational, randomized, placebo-controlled trial in patients with TRS (study 003) in 2023, as part of its ongoing Phase II/III development plan for evenamide.

The first potentially pivotal study of this development program, study 008A, with evenamide as add-on therapy in patients with chronic schizophrenia experiencing inadequate response to their current antipsychotics (but not diagnosed as having TRS) is enrolling patients, and results are expected in 2023. Newron continues its dialogue with industry partners around potential future collaboration opportunities for the development of evenamide.