FDA flags four deaths in Newron's schizophrenia drug studies

On October 8, 2026, Newron Pharmaceuticals announced that the US FDA flagged four deaths among patients treated with its experimental schizophrenia drug, evenamide, compared to one death in the placebo group. The FDA characterized the deaths as a potential safety signal for fatal cardiac arrhythmias, maintaining a clinical hold on US trials. Newron is reviewing the feedback, noting that investigators deemed three of the deaths unrelated to the drug, and plans to submit a formal response.

FDA safety concerns and patient deaths

• ▪Trial investigators considered three of the four FDA-flagged patient deaths unrelated to evenamide, while one death was deemed possibly related because two autopsies failed to determine a cause of death
• ▪The US Food and Drug Administration flagged four deaths among patients treated with evenamide across all clinical studies, compared with one death among patients who received a placebo

Mechanism of evenamide and cardiovascular risks

• ▪Evenamide can cause a small shortening of the QTc interval on an electrocardiogram, which lacks an established risk threshold and is not reliably excluded by a standard screening ECG
• ▪The US Food and Drug Administration's safety concerns relate to the risk that sodium channel blockers like evenamide may trigger arrhythmias leading to serious cardiovascular events or seizures
• ▪Evenamide is an investigational glutamate modulator that selectively inhibits voltage-gated sodium channels, being studied as an adjunctive therapy for treatment-resistant schizophrenia

FDA clinical hold on evenamide trials

• ▪The US Food and Drug Administration maintained its clinical hold, originally placed in April 2026 following a participant's sudden death, on US patient enrollment in Newron Pharmaceuticals' phase III ENIGMA-TRS 2 evenamide trial as of October 8, 2026
• ▪No US participants have been dosed with evenamide in the ENIGMA-TRS 2 trial, though patients had entered the ENIGMA-TRS 2 screening phase before the FDA's clinical hold

Newron's response and safety data

• ▪Newron Pharmaceuticals is reviewing the US Food and Drug Administration's feedback on evenamide and plans to submit a comprehensive response based on its safety data
• ▪Newron Pharmaceuticals stated it has not identified a pattern of heart abnormalities or irregular rhythms in its preclinical and clinical safety data for evenamide

Global trial progress and upcoming results

• ▪While US enrollment remains on hold, Newron Pharmaceuticals is continuing patient enrollment for evenamide's ENIGMA-TRS clinical trials outside the United States, including adding additional clinical sites
• ▪Newron Pharmaceuticals expects to announce results from the 12-week primary endpoint assessment of its ongoing ENIGMA-TRS 1 trial in Europe, Asia, Latin America, and Canada in early 2027

Debatable claims

• ▪Trial investigators are more qualified than regulators to determine if patient deaths are drug-related
• ▪The FDA's clinical hold on Newron's evenamide trials is justified
• ▪Newron should suspend evenamide clinical trials outside the United States
• ▪For treatment-resistant schizophrenia, potential efficacy matters more than unproven cardiac safety risks