MILAN, Italy, and MORRISTOWN, N.J. — October 8, 2026

Newron Pharmaceuticals S.p.A. announced that it has received written communication from the U.S. Food and Drug Administration (FDA) regarding the clinical hold at U.S. study sites in its Phase 3 ENIGMA-TRS 2 trial evaluating evenamide for treatment-resistant schizophrenia (TRS). The company is reviewing the agency’s feedback and the available safety data before preparing its response. The clinical hold remains in effect at U.S. sites.

FDA Raises Potential Cardiac Safety Concern

The FDA identified a potential safety signal following four deaths among patients treated with evenamide across its clinical studies, compared with one death among placebo recipients. Investigators considered three of the four deaths in the evenamide group unrelated to treatment, while one was considered possibly related because autopsies did not establish a definitive cause. The agency noted that a fatal arrhythmic mechanism could not be definitively excluded. Newron stated that its safety review includes more than 10,000 ECGs and input from independent cardiac electrophysiologists, and that it has not observed a pattern of cardiac abnormalities or arrhythmias to date.

Phase 3 Enrollment Continues Outside the United States

Despite the U.S. clinical hold, ENIGMA-TRS 1 enrollment is expected to be completed by mid-October 2026, with topline 12-week data anticipated in the first quarter of 2027. This international Phase 3 trial is evaluating evenamide at 15 mg twice daily and 30 mg twice daily against placebo in patients with treatment-resistant schizophrenia. Enrollment in ENIGMA-TRS 2 continues at sites outside the United States, and additional clinical sites are being added as planned. The second study is designed to evaluate 15 mg twice daily over 12 weeks.

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Company Evaluates Next Steps for Evenamide

Newron is assessing the full safety dataset and potential additional cardiac screening and monitoring measures for ENIGMA-TRS 2 before responding to the FDA. Evenamide is an investigational glutamate modulator that acts as a selective voltage-gated sodium channel blocker and is being developed as an add-on treatment for patients whose schizophrenia responds inadequately to existing therapies. The U.S. clinical hold remains unresolved, and further development at U.S. study sites will depend on the regulatory review and subsequent actions.

Source::Newron Pharmaceuticals, press release