FDA Keeps U.S. Enrollment Hold on Newron's Phase 3 ENIGMA-TRS 2 Schizophrenia Trial
核心洞察
The FDA has told Newron Pharmaceuticals (搜索) that the hold on new patient enrollment at U.S. sites in the Phase 3 ENIGMA-TRS 2 study of evenamide will remain in place.
Enrollment continues outside the United States, and Newron is expanding sites and recruitment across Europe, Asia and Latin America, with about 80 patients screened so far.
The hold followed Newron's April 29, 2026 notification to the FDA of the sudden unexpected death of a study participant at a site outside the U.S., which the investigator assessed as unrelated to treatment.
Newron Pharmaceuticals (搜索) said the U.S. Food and Drug Administration has informed the company that the hold on enrollment of new patients at U.S. sites in the Phase 3 ENIGMA-TRS 2 study of evenamide will remain in place. The company disclosed the decision on September 25, 2026, adding that it expects written communication from the FDA with additional information on the decision and any further protocol changes that may be required to lift the hold.
Enrollment in ENIGMA-TRS 2 continues outside the United States. Newron is initiating an expansion of clinical sites and recruitment in Europe, Asia and Latin America. Approximately 80 patients have entered screening to date, and the study is expected to enroll at least 400 patients following successful completion of a 42-day screening period.
Trial Design and Dose
ENIGMA-TRS 2 is a 12-week, randomized, double-blind, placebo-controlled Phase 3 study evaluating the efficacy, tolerability and safety of evenamide at 15 mg twice daily compared with placebo. It is being conducted at centers in the U.S. and selected additional countries, using the same screening procedure as ENIGMA-TRS 1. The study was initiated in the U.S. in December 2025 following approvals from the FDA and the Institutional Review Board, and is currently ongoing in four countries.
Evenamide is an investigational first-in-class glutamate (搜索) modulator designed to target excessive glutamate release in patients with treatment-resistant schizophrenia (搜索), a population that often has limited treatment options despite existing antipsychotic therapies. Newron states that clinical trial results to date show improvements across key efficacy measures that increase over time, along with a favorable safety profile it describes as uncommon for available antipsychotic medications.
Origin of the Clinical Hold
On April 29, 2026, Newron reported the FDA hold on enrollment of new patients at U.S. sites after notifying the agency of the sudden unexpected death of a study participant at a clinical site outside the United States. The investigator assessed the event as unrelated to study treatment. Newron informed the independent international safety monitoring board for the overall ENIGMA-TRS program, which reviewed the event and recommended that the studies continue as designed. While U.S. patients entered screening, no U.S. patients have been dosed with evenamide in the study.
"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," said Ravi Anand, Chief Medical Officer of Newron.
ENIGMA-TRS 1 Progress and Readout Timing
The larger Phase 3 study, ENIGMA-TRS 1, remains ongoing across 20 countries in Europe, Asia, Latin America and Canada. It is a 52-week, randomized, double-blind, placebo-controlled trial evaluating evenamide at 15 mg twice daily and 30 mg twice daily in patients with treatment-resistant schizophrenia (搜索) who meet Treatment Response and Resistance Psychosis international consensus criteria. Patients enrolled are on second-generation antipsychotics, including clozapine.
Newron expects ENIGMA-TRS 1 to enroll at least 600 patients by mid-October 2026. The primary assessment of efficacy and safety will be performed 12 weeks after randomization, with the primary efficacy endpoint defined as change from baseline in Positive and Negative Syndrome Scale (PANSS) scores at 12 weeks. After that initial period, the study continues double-blind and placebo-controlled until the 26- and 52-week time points. Newron expects to announce results from the 12-week primary endpoint assessment in the first quarter of 2027.
Development and Commercialization Partners
Newron has signed development and commercialization agreements for evenamide with EA Pharma (搜索), a subsidiary of Eisai, for Japan and other Asian territories, and with Myung In Pharm (搜索) for South Korea. The company's first marketed product, Xadago (safinamide), holds marketing authorization for Parkinson's disease in the European Union, Switzerland, the UK, the USA, Australia, Canada, Latin America, Israel, the United Arab Emirates, Japan and South Korea, and is commercialized by Zambon (搜索), with Supernus Pharmaceuticals holding U.S. marketing rights and Meiji Seika (搜索) responsible for development and commercialization in Japan and other key Asian territories.