The company, which focuses on the development of therapies for patients with diseases of the central nervous system (CNS) said the ‘never reported before’ results from its open-label study evaluating evenamide.
The company reports the data demonstrated that treatment with evenamide was associated with sustained clinically significant benefits that increased throughout the one-year course of treatment.
The results at one year show the addition of evenamide to antipsychotics was well-tolerated.
A treatment-emergent adverse event (TEAE) is an adverse event that occurs only once treatment has started, and this study had few dropouts in relation and no pattern of motor or CNS symptoms, weight gain, sexual dysfunction, or laboratory/electrocardiogram (ECG) abnormalities.
With 161 TS patients randomized in the study, 75% completed a year of treatment. Causes for attrition, the loss of study units from a sample, 14.3% withdrawal of consent, 5.6% not rolling over into the extension study, 3.1% lost to follow-up and adverse dropouts, 1.9%.
Gradual and sustained improvement
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. 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 a clinically important reduction in disease severity.
Approximately 90% of the patients who had responded to the treatment by a clinically important reduction, which was greater than or the same as 20% from baseline on the PANSS total score at six months (approximately 45%) maintained their response at one year.
Ravi Anand, Newron’s chief medical officer, said: “Treatment with evenamide as an add-on to antipsychotics in TRS patients has produced benefits that have never been reported before. Despite these patients being on therapeutic doses of antipsychotics, evenamide treatment was associated with clinically important improvement.”
Anand said that 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 criteria.
Transforming the outlook for TSR patients
He added: “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. The above results, if replicated, would transform not only the management but also the societal outlook for patients with TRS.”
Newron says 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, such as the addition of a glutamate modulator to background antipsychotics.
Furthermore, the company says the findings support the initiation of a potentially pivotal, phase 3, randomized, double-blind, placebo-controlled study of two doses of evenamide at 15 and 30 mg bid) as an add-on treatment in patients with TRS.
John Kane is a professor of psychiatry and molecular medicine, at The Donald and Barbara Zucker School of Medicine, Hempstead New York professor.
He said: “Even though these results come from an open-label study performed largely in India, the continued improvement on all efficacy measures in TRS patients for one year, together with the finding that approximately 50% of these patients improved to an extent that they no longer met criteria for TRS is highly encouraging. Furthermore, the finding that 25% of TRS patients achieved remission is very unexpected. These results should lead to expediting the conduct of a placebo-controlled international trial to replicate these results.”