Newron Pharmaceuticals S.p.A. (SIX: NWRN, XETRA: NP5), a biopharmaceutical company focused on developing novel therapies for central and peripheral nervous system diseases, announced on October 8, 2026, that it has received written communication from the U.S. Food and Drug Administration (FDA) regarding the clinical hold at U.S. study centers in its Phase 3 ENIGMA-TRS 2 study with evenamide. The company is conducting a thorough review of the FDA's feedback and the available data and intends to submit its response upon completion.
The FDA's concern relates to the known risk that certain sodium channel blockers may trigger arrhythmias, which can lead to serious cardiovascular events or seizures. Evenamide is a selective voltage-gated sodium channel blocker. In its written communication, the FDA noted four deaths among patients treated with evenamide across all clinical studies to date, compared with one death among patients receiving placebo. Three of the four deaths were considered unrelated to evenamide by study investigators, while one was considered "possibly related" because two autopsies could not identify a definitive cause. The FDA characterized these deaths as a potential safety signal based on the possibility of a fatal arrhythmic mechanism that cannot be definitively excluded through post hoc adjudication.
Evenamide is also known to cause a very small shortening of the QTc interval on an electrocardiogram (ECG). Unlike QTc prolongation, there is no established risk or intervention threshold for QTc shortening, and a standard screening ECG does not reliably exclude latent sodium-channel disorders in asymptomatic patients.
Newron is reviewing the FDA's feedback and the full body of safety data generated across the evenamide development program, which includes more than 10,000 ECGs from approximately 700 evenamide-treated subjects and input from independent cardiac electrophysiologists. The company has not observed a pattern of cardiac abnormalities or arrhythmias in the preclinical and clinical safety data generated with evenamide to date, including a thorough QT study and more than 5,000 ECGs from over 700 patients with schizophrenia. As part of its response, Newron is also evaluating additional cardiac screening and monitoring measures for ENIGMA-TRS 2.
"We remain confident in the ENIGMA-TRS studies and encouraged by the program's progress. Our belief in the potential of evenamide and its novel mechanism for patients with treatment-resistant schizophrenia remains strong," said Ravi Anand, MD, Chief Medical Officer of Newron. "Patient safety is our utmost priority. Our team is working with high commitment to complete a thorough review of the FDA's feedback and the available data, and to submit our response upon its completion. Our assessment is supported by the substantial body of preclinical and clinical safety data generated with evenamide. To date, we have not observed a pattern of cardiac abnormalities or arrhythmias. The four deaths among patients treated with evenamide represent an incidence of 0.56%, compared with one death and an incidence of 0.27% among patients receiving placebo. When adjusted for duration of treatment, the mortality rate was 1.31 per 100 patient-years for evenamide compared with 1.81 per 100 patient-years for placebo."
Professor Dr. Peter Falkai, Chair of the Department of Psychiatry and Psychotherapy at LMU University of Munich, provided context on the disease: "Schizophrenia is a tragic disease that affects patients in the teenage (males) and early twenties (females) and has a devastating effect on their lives. In addition to multiple episodes of psychosis and hospitalization, patients need to take antipsychotic medication with debilitating side-effects that makes them suffer from cardiac, hormonal, metabolic and motor disorders. Furthermore, schizophrenia reduces life-expectancy by about 10 years. TRS, a more severe form of the disease in which patients do not respond to any medication, reduces longevity by about 20 years."
Newron continues to advance the Phase 3 ENIGMA-TRS development program. ENIGMA-TRS 1 enrollment is expected to be completed by mid-October, with topline 12-week data expected in Q1 2027. ENIGMA-TRS 2 enrollment continues outside the U.S., and additional clinical sites are being added as planned. The FDA clinical hold remains in place at U.S. study centers; no U.S. patients have been dosed with evenamide in the study.
The company will host an investor update conference call today at 3.30 pm CEST to provide a brief update on the FDA clinical hold and ENIGMA-TRS development program. Access details are available here.
For more information, visit https://www.newron.com and connect on LinkedIn. View the original release on www.newmediawire.com.
