Newron Pharmaceuticals has been informed by the US Food and Drug Administration (FDA) that the hold on the enrollment of new patients will remain in place at US sites in the phase 3 ENIGMA-TRS 2 study with evenamide. Enrollment in the study continues outside the US.

Newron anticipates receiving a written communication from the FDA with additional information regarding its decision and any further potential protocol changes that may be required to lift the hold.

Evenamide targets the modulation of excessive release of glutamate in patients suffering from Treatment-Resistant Schizophrenia (TRS).

Newron is initiating the expansion of clinical sites and enrollment for ENIGMA-TRS 2 in Europe, Asia and Latin America. To date, approximately 80 patients have entered screening. The study is expected to enroll at least 400 patients following successful completion of the 42-day screening period.

The ENIGMA-TRS 1 study is currently ongoing in 20 countries, with ENIGMA-TRS 2 ongoing in 4 countries.

Ravi Anand, Chief Medical Officer, Newron, said, “Newron is highly confident in the significant body of clinical and preclinical safety data for evenamide, and we will continue to work constructively with the FDA to address the clinical hold.”

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 to be 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 Q1 2027.

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 US Food and Drug Administration (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.

On April 29, 2026, Newron reported a hold by the FDA on the enrollment of new patients in the US sites of the study, following the company’s notification to the agency of the sudden unexpected death of a study participant at a clinical site outside the US. The investigator assessed the event as unrelated to study treatment.

Newron has informed the independent international safety monitoring board for the overall ENIGMA-TRS program, which has reviewed the event and recommended that the studies continue as designed.

While the US patients entered screening, none of them have been dosed with evenamide, in the study.