Newron completes ENIGMA-TRS 1 screening with 12-week data due Q1 2027
Newron Pharmaceuticals has completed the screening phase for ENIGMA-TRS 1, its pivotal Phase 3 study of evenamide as an add-on therapy in treatment-resistant schizophrenia (TRS). The Milan- and Morristown-based biopharmaceutical company said it expects to finalise enrolment of at least 600 patients around mid-October 2026, with topline results from the 12-week treatment period anticipated in the first quarter of 2027.
The trial enrolled more broadly than the headline figure suggests. As of the announcement date, 996 patients had entered screening, 411 had been randomised to treatment, and a further 352 remained in the 42-day screening window. An Independent Eligibility Assessment Committee, comprising three international schizophrenia specialists, applies the Treatment Response and Resistance in Psychosis (TRRIP) consensus criteria before randomisation, a rigorous step Newron says is designed to ensure the enrolled population genuinely meets the TRS definition.
Trial design and candidate profile
ENIGMA-TRS 1 is a one-year, randomised, double-blind, placebo-controlled study evaluating evenamide at two doses (15 mg twice daily and 30 mg twice daily) against placebo, added on top of existing second-generation antipsychotics including clozapine. The primary efficacy endpoint is change from baseline in the Positive and Negative Syndrome Scale (PANSS) at 12 weeks, with further assessments at 26 and 52 weeks.
Evenamide acts by selectively blocking voltage-gated sodium channels, normalising aberrant glutamate release without affecting baseline glutamate levels. This mechanism is distinct from all currently approved antipsychotics, which primarily target dopamine receptors. The company positions evenamide as a potential first-in-class glutamate modulator and, if approved, as the first therapy specifically indicated as an add-on for TRS patients.
Ravi Anand, chief medical officer at Newron, said the pace of enrolment reflected "enthusiasm among investigators worldwide for evenamide and its novel glutamate-modulating mechanism, together with the well-designed ENIGMA-TRS 1 study." Newron has previously reported efficacy signals in Phase 2 and an earlier Phase 3 study (008A), citing improvements across multiple psychopathology measures and a tolerability profile it describes as favourable.
Market context and competitive landscape
TRS represents a substantial and chronically underserved patient segment. Estimates suggest between one-third and half of all people with schizophrenia derive inadequate benefit from standard antipsychotic regimens, and approximately 15% meet TRS criteria from illness onset. Clozapine remains the only agent with a specific evidence base in TRS, yet its side-effect burden limits broader use, leaving a substantial population with few alternatives.
The glutamatergic hypothesis of TRS has attracted growing scientific attention, underpinned by evidence of abnormal glutamate neurotransmission in patients who fail dopaminergic treatments. Several academic and industry groups have explored NMDA receptor modulators and glycine-site agents in this space, though none has yet achieved regulatory approval as a TRS-specific add-on. If ENIGMA-TRS 1 delivers a positive primary endpoint, Newron would be well positioned to file with both the FDA and EMA, with commercialisation partnerships already in place for Japan and South Korea through EA Pharma and Myung In Pharm respectively.
Investors will focus on the Q1 2027 topline readout, scrutinising the magnitude of PANSS improvement and the safety profile at the two dose levels. A positive result would likely prompt out-licensing discussions for major Western markets, where Newron has not yet announced a commercial partner.