FDA Cites Four Deaths on Newron's Schizophrenia Drug Evenamide, Keeps U.S. Trial Hold in Place

Newron Pharmaceuticals said Thursday, Oct. 8, that the FDA has put in writing why it is keeping a clinical hold on the company's experimental schizophrenia drug in the United States. The agency counts four deaths among patients treated with evenamide across all of its clinical studies, compared with one among patients on placebo.

The FDA calls the four deaths a potential safety signal. Newron says the agency's concern rests on the possibility of a fatal arrhythmic mechanism that "cannot be definitively excluded through post hoc adjudication."

What the FDA flagged

Evenamide is a glutamate modulator that works by selectively blocking voltage-gated sodium channels in the brain. It is being tested as an add-on therapy for treatment-resistant schizophrenia.

The FDA's stated worry is a class concern. Certain sodium channel blockers are known to trigger arrhythmias, which can lead to serious cardiovascular events or seizures, according to Newron's description of the agency's letter.

Of the four deaths in the evenamide group, study investigators considered three unrelated to the drug. The fourth was rated "possibly related" because two autopsies failed to identify a definitive cause of death.

Newron puts the incidence at 0.56% for evenamide patients and 0.27% for placebo patients. The absolute counts are tiny: five deaths in total across the program.

How the hold started

The FDA halted U.S. enrollment in the Phase 3 ENIGMA-TRS 2 trial in April 2026 after a participant died at a trial site outside the U.S. Newron said at the time that the death was unrelated to evenamide.

The hold remains at U.S. study centers. Patients in the U.S. entered screening, but none has been dosed with evenamide, Newron said.

Enrollment in ENIGMA-TRS 2 continues in other countries, and the company says it is adding clinical sites as planned.

The company's position

Newron says it is reviewing the FDA's feedback along with the full safety record and will submit a response once that review is done. It has not given a date.

"Our team is working with high commitment to complete a thorough review of the FDA's feedback and the available data," Chief Medical Officer Ravi Anand said in the company's release. "Our assessment is supported by the substantial body of preclinical and clinical safety data generated with evenamide."

The company also says it has not observed a pattern of cardiac abnormalities or arrhythmias in its preclinical and clinical data. That data includes ECGs from roughly 700 patients who received evenamide. Anand said Newron remains "confident in the ENIGMA-TRS studies" and that its belief in the drug's novel mechanism "remains strong."

The FDA and the company are reading the same record differently. The agency says a fatal arrhythmia cannot be ruled out after the fact. Newron says three of the four deaths were judged unrelated by investigators and that its ECG data shows no arrhythmia pattern.

The ECG wrinkle

Newron disclosed one more detail. Evenamide produces a very small shortening of the QTc interval on an ECG.

The company says that, unlike QTc prolongation, shortening has no established risk or intervention threshold. It also says a standard screening ECG "does not reliably exclude latent sodium-channel disorders in asymptomatic patients."

Newron said it is assessing additional cardiac screening and monitoring measures for the program.

What continues

The other pivotal trial, ENIGMA-TRS 1, is unaffected by the U.S. hold. It is running in Europe, Asia, Latin America and Canada.

Newron expects to finish enrollment by mid-October. The company has said it is aiming for at least 600 patients across 20 countries. Topline results from the 12-week primary endpoint are expected in the first quarter of 2027.

Newron, which is listed on the SIX Swiss Exchange and XETRA, scheduled a management call for 3:30 p.m. CEST on Thursday to discuss the update.

Its written response to the FDA has no announced date. The agency has not said what would lift the hold, and Newron has not said what cardiac monitoring it would add. The first quarter 2027 data from ENIGMA-TRS 1 will be the next major test of the drug.