One-year data from a Phase II study of Newron’s schizophrenia candidate evenamide showed sustained efficacy and continued improvements in symptoms of psychosis and disease severity.
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One-year interim data from a Phase II study of Newron Pharmaceuticals’ schizophrenia candidate evenamide showed sustained efficacy and continued improvements in symptoms of psychosis and disease severity, the Milan-based company reported Thursday.
Evenamide, an orally available blocker of voltage-gated sodium channels, is being trialed in patients with treatment-resistant schizophrenia (TRS) in combination with antipsychotic medicines except for clozapine. Readouts for the candidate’s six-week and six-month efficacy have previously been reported.
At the one-year follow-up, patients treated with evenamide showed a 50% improvement in the Positive and Negative Syndrome Scale (PANSS) score as compared to the initial benefit documented at the six-week time point. This effect was statistically significant, according to the announcement.
The proportion of responders – patients who experienced a clinically meaningful increase in PANSS score – was nearly three times as high as during week six.
Newron also measured improvement in illness severity using the Clinical Global Impression of Severity (CGI-S), which showed significantly better results at 1 year compared with baseline. Twice as many patients achieved highly meaningful improvement in CGI-S at 1 year than at week 6.
While clozapine is the standard treatment for TRS, more than half of these patients do not respond to it, Jean-Pierre Lindenmayer, M.D., director of research, psychopharmacology research unit, Nathan Kline Institute for Psychiatric Research, Manhattan Psychiatric Center, said in a statement.
Evenamide demonstrates a “particularly unusual” pattern of improvement that occurs gradually over a year and is sustained thereafter, Lindenmayer said.
The drug candidate also appears to have a “completely novel mechanism of action,” which could lead to new avenues of TRS treatment, he continued.
Newron is preparing for a potentially pivotal randomized and placebo-controlled trial in TRS, set to launch in 2023. A previously initiated potentially pivotal study of evenamide is currently enrolling and results are expected this year.
A New Day in Neuropsychiatrics
Evenamide is a New Chemical Entity that is designed to treat schizophrenia by inhibiting voltage-gated sodium channels, thereby normalizing the release of glutamate and modulate repetitive neuronal firing.
In pre-clinical studies, the candidate improved psychosis symptoms significantly better than placebo, Newron reported. Of note, evenamide had no detectable activity on more than 130 neurotransmitters, enzymes or transporters commonly targeted by other antipsychotic medications.
Evenamide is part of a budding paradigm shift in neuropsychiatry that seeks to apply a precision approach to these conditions by elucidating the various mechanisms underpinning conditions such as schizophrenia, depression and anxiety – and develop treatments targeting these mechanisms and specific patient groups.
Joining Newron in this movement is Karuna Therapeutics, which is gearing up to submit a New Drug Application for schizophrenia hopeful KarXT (xanomeline-trospium) by mid-2023.
Like evenamide, KarXT adopts a novel approach to schizophrenia. Whereas most drugs for this condition are classified as antipsychotics and target the D2 dopamine and 5HT-52A serotonin receptors, Karuna’s candidate works through the M1 and M4 muscarinic receptors. This different mechanism of action allows it to avoid common side effects associated with antipsychotic agents.
If approved, it would be the first therapeutic approved by the FDA to treat the negative symptoms of schizophrenia.
KarXT demonstrated its efficacy in the EMERGENT-2 study, where it induced a nearly 10-point improvement in PANSS relative to placebo.
