Newron Pharmaceuticals has completed enrolment of 618 patients in its Phase 3 trial of evenamide for treatment-resistant schizophrenia, with initial results expected in Q1 2027.

Phase 3 trial recruits 618 patients

Newron Pharmaceuticals has completed enrolment in ENIGMA-TRS 1, a Phase 3 clinical trial evaluating evenamide as an add-on treatment for patients with treatment-resistant schizophrenia.

The international study randomised 618 patients across more than 80 clinical trial centres in 19 countries spanning Europe, Asia, Latin America and Canada. The company expects to report topline results from the primary 12-week assessment in the first quarter of 2027.

Evenamide is an investigational drug designed to modulate glutamate release. The trial is evaluating whether adding the treatment to existing second-generation antipsychotics can improve outcomes for patients whose schizophrenia has not responded adequately to treatment.

Participants were randomised to receive evenamide at doses of 15 mg or 30 mg twice daily, or placebo, alongside their existing antipsychotic treatment. Eligible patients could be receiving clozapine, an antipsychotic commonly used to treat schizophrenia that has not responded adequately to other medicines.

According to Newron, 996 patients entered screening, of whom 618 met the study’s eligibility criteria and were randomised.

Ravi Anand, chief medical officer at Newron, said: “Reaching this important milestone in the ENIGMA-TRS 1 study reflects the tremendous commitment of investigators and clinical teams, alongside the close collaboration of our academic and regulatory partners, as well as the patients and their families. The study is particularly important given the complexity of conducting a first long-term, randomized, double-blind, placebo-controlled add-on study in patients with TRS, an area of considerable unmet medical need.”

Results will assess schizophrenia symptoms

The primary endpoint is the change from baseline in scores on the Positive and Negative Syndrome Scale (PANSS) after 12 weeks of treatment. The scale is used to assess the severity of schizophrenia symptoms, including positive symptoms such as hallucinations and delusions, negative symptoms such as reduced motivation, and general psychopathology.

The initial assessment will examine the efficacy and safety of both evenamide doses compared with placebo. The study will then continue under double-blind, placebo-controlled conditions, with further assessments planned at 26 and 52 weeks.

The longer follow-up will provide additional information about the treatment’s safety and efficacy over time. However, the results of the initial 12-week assessment will be an important milestone in determining whether evenamide warrants further development for treatment-resistant schizophrenia.

The study’s completion does not establish that the drug is effective. Its potential benefit will depend on the clinical results, including whether any improvement in symptoms is meaningful and supported by the trial data.

Second Phase 3 study remains ongoing

Newron is also conducting ENIGMA-TRS 2, a separate Phase 3 trial evaluating evenamide in patients with treatment-resistant schizophrenia.

The second study plans to include at least 400 patients and is evaluating the 15 mg twice-daily dose against placebo over 12 weeks. Recruitment is taking place at centres in Asia and Latin America, with additional European sites planned.

The US Food and Drug Administration (FDA) clinical hold remains in place at US centres participating in ENIGMA-TRS 2. No patients at those centres have received evenamide, according to the company.

The two studies form part of Newron’s clinical development programme for evenamide, which targets glutamate signalling rather than the mechanisms targeted by many existing antipsychotic medicines.

Treatment-resistant schizophrenia remains a challenge in psychiatric care, as some patients continue to experience significant symptoms despite treatment with antipsychotic drugs. Clinical data from ENIGMA-TRS 1 will help establish whether evenamide offers a viable additional treatment option for this population.

The next major milestone is the expected Q1 2027 release of the 12-week results.