Newron Pharmaceuticals S.p.A. reported positivefinal, one-year results from its open label study 014/015, evaluating its investigational drug evenamide as an add-on to antipsychotics for the management of treatment-resistant schizophrenia (TRS). The data demonstrated that treatment with evenamide was associated with sustained clinically significant benefit that increased throughout the one-year course of treatment. Final results at one-year indicate that the addition of evenamide to antipsychotics was well tolerated, with a low incidence of treatment-emergent adverse dropouts, and without any pattern of motor or CNS symptoms, weight gain, sexual dysfunction or laboratory/electrocardiogram (EKG) abnormalities.

Of the 161 TRS patients randomized in the study, 75% completed one-year of treatment: the causes of attrition were withdrawal of consent (14.3%), not rolling over into extension study (5.6%), lost to follow up (3.1%), and adverse dropouts (ADOs) (1.9%). Study 014/015 key findings and conclusions at one-year (full study population): Efficacy results based on change from baseline in the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression of Severity (CGI-S), and the Strauss Carpenter Level of Functioning (LOF) showed a statistically significant improvement at one year (p-value < 0.001: paired t-test, OC/LOCF). All efficacy scales showed gradual and sustained improvement.

In contrast to common clinical experience, no patient ?relapsed? during the one-year treatment period. More than 70% of the patients experienced clinically important reduction in disease severity.

Approximately 90% of the patients who had responded to the treatment by a clinically important reduction (= 20% from baseline) on PANSS total score at six months (~45%) maintained their response at one-year. Review of the efficacy data indicated that treatment with evenamide resulted in approximately 50% of patients at one-year no longer meeting any of the protocol severity criteria used to diagnose treatment resistance. 25% of all patients achieved ?remission"), never described before in TRS patients.

The durability and longevity of these clinical benefits is unprecedented and strongly raises the expectation for an improved evidenced-based treatment strategy for TRS patients, i.e., the addition of a glutamate modulator to background antipsychotics. Furthermore, the findings support the initiation of a potentially pivotal, Phase III, randomized, double-blind, placebo-controlled study of two doses of evenamide (15 and 30 mg bid) as an add-on treatment in patients with TRS. Regardless of the criteria applied for remission in patients with chronic schizophrenia, approximately 25% of these treatment-resistant patients were considered in remission using the most quoted criteria1.

Although these data are derived from an open-label study, the increasing benefit over time from six-weeks to one-year suggests that the glutamate modulating effect of evenamide could lead to a progressive and long-standing alteration in brain processes synergizing with the effect of antipsychotics to which the patient had become resistant.