Newron Pharmaceuticals S.p.A. has announced what it says are “very compelling new results” from the first 100 enrolled patients to have reached the six-month timepoint in its international study of evenamide as an add-on to an antipsychotic (excluding clozapine) in patients with moderate to severe treatment-resistant schizophrenia (TRS), who were not responding to their current antipsychotic medication.
Eighty-five of the 100 patients completed the 30-week treatment period with evenamide. The results follow on from the company’s announcement on June 7, 2022, summarizing the data from an interim analysis of the first 100 patients to have finished six weeks of treatment in this study.
Newron is an Italian-headquartered biopharmaceutical company focused on the development of novel therapies for patients with diseases of the central and peripheral nervous system (CNS).
The results demonstrated a continued improvement in TRS symptoms after six months of treatment with evenamide, as well as a substantially greater proportion of patients experiencing a meaningful improvement when compared to six weeks of treatment.
A significant proportion of patients with schizophrenia show virtually no beneficial response to antipsychotics (APs) despite adequate treatment, leading to a diagnosis of treatment-resistant schizophrenia (TRS). TRS is defined as no, or inadequate, symptomatic relief despite treatment with therapeutic doses of two APs from two different chemical classes for an adequate period. About 15% of patients develop TRS from illness onset, and about one-third of patients overall.
Increasing evidence supports abnormalities in glutamate neurotransmission in TRS, not targeted by current APs, along with normal dopaminergic synthesis, explaining the lack of benefit of most typical and atypical APs.
Stephen R. Marder, Daniel X. Freedman Professor of Psychiatry, vice chair for education of the Semel Institute for Neuroscience at UCLA, director at the Desert Pacific Mental Illness Research, Education and Clinical Center, said: “The results from study 014/015 are very encouraging. Evenamide was well tolerated with few adverse effects and 85 of 100 patients remained on treatment at 30 weeks. Moreover, the magnitude of the improvements experienced by these TRS patients, not responding to their current antipsychotic, on evenamide was substantial, improved over time and was likely to be clinically meaningful. If these results are confirmed by a planned randomized and placebo-controlled trial, evenamide would be the first medication that could be added to an antipsychotic to improve symptoms in treatment refractory schizophrenia.”
Ravi Anand, Newron’s chief medical officer, said: “New therapeutic options are desperately needed for treatment-resistant schizophrenia that occurs in approximately one third of patients. These results from studies 014/015 make us excited about the clinical potential of evenamide. The data comparing the impact of evenamide at six weeks versus six months, reported today, suggest that not only was there sustained improvement in the key measures, but the proportion of patients achieving clinically meaningful improvement increased over time. Confirmation in a controlled trial would support the hypothesis that evenamide treatment is associated with an attenuation of abnormal glutamate activity noted in patients with TRS.”
Full results of the Newron study
The enrollment of study 014 has been completed with 161 subjects. Newron expects to announce the full results from the study in March 2023. The extension arm, study 015, is ongoing and will provide results of evenamide treatment for up to one year from the first 100 patients by Q2 2023.
Newron expects to initiate a potentially pivotal, multinational, randomized, 10-week, placebo-controlled study (003) in TRS patients 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 classed as having TRS), is continuing to enroll patients, and results are expected in 2023.
About Newron’s evenamide
Newron’s Evenamide, an orally available new chemical entity, blocks voltage-gated sodium channels (VGSCs) and is devoid of biological activity at more than 130 other CNS targets. It normalizes glutamate release induced by aberrant sodium channel activity (veratridine-stimulated), without affecting basal glutamate levels, due to inhibition of VGSCs.
Combinations of ineffective doses of evenamide and other APs, including clozapine, were associated with benefit in animal models of psychosis, suggesting synergies in mechanisms that may provide benefit in patients who are poor responders to current APs, including clozapine.