Newron Pharmaceuticals has highlighted new preclinical findings published in Neuropsychopharmacology that explore the mechanism and potential therapeutic role of evenamide in schizophrenia.

Researchers at the University of Pittsburgh used the methylazoxymethanol acetate (MAM) neurodevelopmental animal model of schizophrenia, which replicates anatomical, behavioural, neurochemical, and physiological features of the disorder. The study examined the effects of acute evenamide administration on hippocampal hyperexcitability, hyperdopaminergic state, social deficits, and recognition memory.

Schizophrenia, affecting around 1% of the global population, presents with positive, negative, and cognitive symptoms. Existing dopamine D2 antagonist-based antipsychotics primarily address positive symptoms, leaving cognitive and social deficits largely untreated. Hyperexcitability in the limbic hippocampus is recognised as a key pathological feature and therapeutic target.

Evenamide is a selective voltage-gated sodium channel blocker and glutamate modulator. In the study, it selectively inhibited hyperactive neurons in the hippocampus, normalised excessive synaptic glutamate linked to NMDA receptor hypofunction, and was reported to have no activity at other central nervous system targets.

Key findings included improvements in positive, negative, and cognitive symptoms in the MAM model following a single systemic dose of evenamide. Time-course analysis indicated that effects persisted beyond drug elimination, suggesting a potential influence on neuronal plasticity.

Dr Anthony Grace, senior author of the study, said: “Evenamide is a unique agent acting at the site of the deficit in schizophrenia by reducing hippocampal hyperexcitability. This represents a significant advancement in treatment, as evenamide can downregulate the hyperdopaminergic state without producing D2 blockade-related side effects while also improving behavioural deficits that are not properly treated by current antipsychotic agents.”

Newron noted that these preclinical results align with outcomes from earlier clinical studies. In a Phase 2 trial of treatment-resistant schizophrenia (TRS), patients showed continued improvement in symptoms up to one year after initiating evenamide alongside existing antipsychotic therapy. In a Phase 3 trial in patients unresponsive to second-generation antipsychotics, including clozapine, adding evenamide led to significant improvements on the Positive and Negative Syndrome Scale (PANSS) and higher responder rates.

The company stated that these findings support the ongoing pivotal Phase 3 programme evaluating evenamide as an adjunctive therapy in schizophrenia, including in treatment-resistant cases.