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An experimental add-on antipsychotic called evenamide has reduced the severity of schizophrenia symptoms in patients that don’t respond to current treatments, according to interim results from a small clinical trial run by the Italian firm Newron.

Schizophrenia is a mental health condition that leads to positive symptoms, such as hallucinations, and negative symptoms, which can include impairments to cognition. A large fraction of schizophrenia patients fail to respond to standard antipsychotic drugs and are diagnosed with treatment-resistant schizophrenia (TRS).

“New therapeutic options are desperately needed for treatment-resistant schizophrenia that occurs in approximately one third of patients,” said Ravi Anand, Newron’s Chief Medical Officer, in a public statement.

The results—which the company labeled as “striking”—came from Newron’s trial called study 014, which enrolled 161 patients with TRS from sites in India, Italy and Sri Lanka. The enrolled TRS patients were on a stable, therapeutic dose of a single antipsychotic drug other than clozapine when the trial began, and were randomized to receive different doses of evenamide twice per day in addition to their current medication.

In its latest interim analysis, Newron screened the first 100 patients to reach the six-month time point in study 014 and its ongoing extension arm, study 015. 85 of these patients completed the treatment course, and Newron compared their clinical outcome to baseline and to previous interim results at the six week time point.

After six months of treatment with evenamide, the patients’ schizophrenia symptoms were significantly improved compared to baseline, as measured by the Positive and Negative Syndrome Scale (PANSS), the “gold standard” for assessments in psychotic disorders. Additionally, the proportion of patients that responded to the treatment had doubled from 16.5% at six weeks. Evenamide was also well tolerated with few adverse effects.

According to a statement by Stephen Marder, Daniel X. Freedman Professor of Psychiatry, 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.”

It remains unclear why some schizophrenia patients are resistant to treatment with current antipsychotics. One of the most accepted causes of positive symptoms in schizophrenia is a high amount of the neurochemical dopamine in an area of the brain called the striatum. However, this trend isn’t seen in all patients.

Newron points the finger at abnormalities in glutamate signaling in the brain as an important factor in TRS. Evenamide is designed to block voltage-gated sodium channels in the brain and restore glutamate signalling to a healthy state.

The full results from study 014 are expected in March 2023, and from study 015 in late 2023. If they bear out, Newron expects to launch a potentially pivotal placebo-controlled study of evenamide as an addon treatment in TRS later this year.

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