Newron Pharmaceuticals said the US FDA has placed a clinical hold on new patient enrollment at US sites in its Phase III ENIGMA-TRS 2 study of evenamide in treatment-resistant schizophrenia, following the company's notification to the agency of a sudden unexpected death in a participant at a non-US clinical site.
The FDA hold applies exclusively to new enrollment at US centers in ENIGMA-TRS 2, which was initiated in the US in December 2025 following FDA and Institutional Review Board approvals. The deceased participant's investigator assessed the event as unrelated to study treatment. The independent international safety monitoring board for the overall ENIGMA-TRS program reviewed the event and recommended that both studies continue as designed. Newron's Chief Medical Officer Ravi Anand stated that, across the evenamide development program to date, there is no increase in the risk of mortality between evenamide- and placebo-treated patients based on duration of treatment. No efficacy data were reported in connection with this announcement.
The ENIGMA-TRS 2 trial is a 12-week, randomized, double-blind, placebo-controlled Phase III study planned to enroll at least 400 patients with treatment-resistant schizophrenia, evaluating evenamide 15 mg twice daily versus placebo, with efficacy and safety analysis at the 12-week endpoint. The hold is limited to US sites; ENIGMA-TRS 2 has received regulatory approval in Argentina and India and is in the final stages of approval in Colombia and Malaysia. The parallel ENIGMA-TRS 1 study, a 52-week international Phase III trial enrolling at least 600 patients across 21 countries and evaluating both 15 mg and 30 mg twice-daily doses, continues with over 400 patients enrolled; Newron expects to report 12-week primary endpoint results in the fourth quarter of 2026. The data from both studies remain blinded, and no interim efficacy findings have been disclosed.