MILAN & MORRISTOWN, N.J. — Newron Pharmaceuticals said the U.S. Food and Drug Administration has placed a hold on enrollment of new patients at U.S. sites in its Phase III ENIGMA-TRS 2 study of evenamide for treatment-resistant schizophrenia.
The company said the enrollment pause is limited to U.S. centers in ENIGMA-TRS 2. Newron’s global ENIGMA-TRS 1 study is continuing, with more than 400 patients enrolled.
Newron, a biopharmaceutical company developing therapies for diseases of the central and peripheral nervous system, said the FDA action followed the company’s notification to the agency of the sudden death of a study participant at a clinical site outside the United States. The investigator assessed the event as unrelated to study treatment.
The company said it also informed the independent international safety monitoring board for the overall ENIGMA-TRS program. Newron said the board reviewed the event and recommended that the studies continue as designed.
Newron said it is working with the FDA and plans to provide the requested information to support resolution of the hold and the resumption of enrollment at U.S. sites for ENIGMA-TRS 2.
“Patient safety remains our highest priority; all patients who enroll in the evenamide program are thoroughly evaluated. The ENIGMA-TRS program with evenamide is monitored by an independent international safety monitoring board. The board has been informed of the event and has concluded that the studies should continue as designed. In the evenamide development program, to date, there is no increase in the risk of mortality between evenamide and placebo-treated patients based on the duration of treatment. Sudden death is not uncommon in patients with schizophrenia,” said Ravi Anand, Newron’s Chief Medical Officer.
Evenamide is being studied for its potential to modulate excessive glutamate release in patients with treatment-resistant schizophrenia. Newron said ENIGMA-TRS 1 is being conducted in 21 countries and continues to enroll patients. ENIGMA-TRS 2 has received regulatory approval in Argentina and India and is in final stages of receiving approval in Colombia and Malaysia.
Schizophrenia is associated with significantly higher mortality and reduced life expectancy compared with the general population. Newron said studies have shown that schizophrenia can reduce life expectancy by 10 to 25 years and that sudden unexpected deaths are noted in at least 20% of mortality cases.
ENIGMA-TRS 1 is an ongoing 52-week, randomized, double-blind, placebo-controlled Phase III study evaluating 15 mg twice-daily and 30 mg twice-daily doses of evenamide against placebo. The study is expected to enroll at least 600 patients at centers in Europe, Asia, Latin America and Canada. The primary efficacy endpoint is the change from baseline in Positive and Negative Syndrome Scale scores at 12 weeks. Newron expects to report results from the 12-week primary endpoint assessment in the fourth quarter of 2026.
ENIGMA-TRS 2 is designed as a 12-week, randomized, double-blind, placebo-controlled Phase III study evaluating the 15 mg twice-daily dose of evenamide against placebo. The study is expected to include at least 400 patients at centers in the United States and selected additional countries. Enrollment of new participants at U.S. sites is paused while Newron addresses the FDA’s request.
