The FDA has flagged four deaths among patients receiving Newron Pharmaceuticals’ investigational schizophrenia drug evenamide as a potential safety signal in its written explanation of a clinical hold on U.S. sites in a phase 3 trial.
The four deaths occurred across all clinical studies of evenamide, compared with one death among patients receiving placebo, according to an Oct. 8 news release from the company. Investigators considered three deaths unrelated to evenamide and one possibly related. The FDA cited the possibility of a fatal arrhythmic mechanism that could not be definitively excluded. The agency’s concern stems from the known risk that some sodium channel blockers, the drug class evenamide belongs to, can trigger arrhythmias.
Bresso, Italy-based Newron reported a mortality incidence of 0.56% among evenamide-treated patients, compared with 0.27% among placebo recipients. When adjusted for treatment duration, mortality rates were 1.31 per 100 patient-years for evenamide and 1.81 per 100 patient-years for placebo.
Newron said it has not observed a pattern of cardiac abnormalities or arrhythmias in its safety data, which includes more than 10,000 electrocardiograms from approximately 700 evenamide-treated subjects. The company is reviewing the FDA’s feedback and evaluating additional cardiac screening and monitoring measures.
The clinical hold, first placed on new enrollment at U.S. sites in April, remains in place at U.S. study centers in the phase 3 ENIGMA-TRS 2 trial, though enrollment continues outside the U.S. No U.S. patients have received evenamide in the study.
Meanwhile, enrollment in ENIGMA-TRS 1 is expected to finish by mid-October, with topline 12-week results expected in the first quarter of 2027.
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