Newron has expanded its disclosure around safety events in its late-stage schizophrenia program, saying four deaths have occurred among patients receiving investigational adjunctive therapy evenamide across all clinical studies to date, compared with one death among patients on placebo. The company said the incidence was 0.56% in the evenamide group versus 0.27% on placebo.
The update comes while the FDA’s hold remains in place on the Phase 3 ENIGMA-TRS 2 study in the U.S. In April, the agency barred further patient enrollment in that trial as it evaluated one patient death at a trial site abroad. Newron said at the time that the death was unrelated to evenamide, but the hold has not been lifted.
The Safety Review
Newron said study investigators consider three of the four deaths in patients receiving evenamide unrelated to treatment. One death may be “possibly related” because a definitive cause of death was not determined after two autopsies.
According to the company, the FDA cited concern about evenamide’s mode of action as a selective voltage-gated sodium channel blocker. Newron noted that certain sodium channel blockers may cause irregular heartbeats that can lead to serious cardiovascular events or seizures.
The company said it is reviewing the FDA’s feedback together with safety data from across the development program. That review includes more than 10,000 ECGs from about 700 patients receiving evenamide. Newron also said it has not observed a pattern of cardiac abnormalities or arrhythmias in the preclinical and clinical safety data generated so far, which it said includes more than 5,000 ECGs from over 700 patients.
Newron is also assessing the addition of further cardiac screening and monitoring measures for the program.
Trial Readout For The Program
The safety issue matters because evenamide is already in two late-stage studies. ENIGMA-TRS 1 is an international, 52-week Phase 3 trial expected to enroll at least 600 patients across 20 countries by mid-October. ENIGMA-TRS 2 is designed as a 12-week study in the U.S. and other select countries.
Given the FDA hold, no U.S. patients in ENIGMA-TRS 2 have received evenamide. Recruitment for that study continues outside the U.S.
That keeps the broader program alive, but with a clear regulatory asymmetry: Newron can still gather ex-U.S. data while the FDA focuses on whether the mechanism and the observed deaths warrant tighter risk controls. For investors and partners, the signal is less about one disclosed event than about whether Newron can preserve a viable U.S. path for a novel mechanism in treatment-resistant schizophrenia.
Newron Chief Medical Officer Ravi Anand said the company remains confident in the ENIGMA-TRS studies and encouraged by the program’s progress. The company’s stock was down slightly in pre-market trading, and management was scheduled to provide a program update on Thursday morning.
