Newron Pharmaceuticals has announced that it had a Type A meeting with the US Food and Drug Administration (FDA) regarding the hold on the enrollment of new patients at US sites of its phase 3 ENIGMA-TRS 2 study of evenamide, as reported on April 29, 2026. Evenamide targets the modulation of excessive release of glutamate in patients suffering from Treatment-Resistant Schizophrenia (TRS).

The face-to-face meeting was constructive and the parties discussed potential actions toward the resolution of issues that led to the hold. Newron, as agreed with the agency, plans to propose changes to address the agency’s concerns.

ENIGMA-TRS 1 is an ongoing, international, 52-week, randomised, double-blind, placebo-controlled phase 3 study evaluating the efficacy, tolerability, and safety of the 15mg BID and 30mg BID therapeutic doses of evenamide compared to placebo. Patients on second-generation antipsychotics, including clozapine, will meet Treatment Response and Resistance Psychosis international consensus criteria for TRS. The study will enroll at least 600 patients at study centers in Europe, Asia, Latin America, and Canada. The first patients were successfully enrolled in August 2025, following the completion of a rigorous 42-day screening period. Patients are currently being enrolled across 15 countries in all target continents.

The primary assessment of efficacy and safety of ENIGMA-TRS 1 will be performed 12 weeks after randomisation to treatment. Following this initial period, the study will continue double-blind and placebo-controlled until the 26- and 52-week time points. The primary efficacy endpoint of the trial will be the change from baseline in the Positive and Negative Syndrome Scale (PANSS) scores at 12 weeks. Newron expects to announce results from the 12-week primary endpoint assessment in QIV 2026.

ENIGMA-TRS 2 is taking place at centers in the US and selected additional countries with the same screening procedure as the ENIGMA-TRS 1 trial. ENIGMA-TRS 2 will include at least 400 patients in a 12-week, randomised, double-blind, placebo-controlled phase 3 study, designed to evaluate the efficacy, tolerability, and safety of the 15mg BID dose of evenamide compared to placebo. In December 2025, ENIGMA-TRS 2 was initiated in the US, following approvals from the FDA and the Institutional Review Board (IRB). The efficacy and safety analysis will be performed at the 12-week point following successful completion of the study.