The article describes the FDA’s safety concern about evenamide and the resulting hold on US enrollment in ENIGMA-TRS 2.
Approach:
Regulatory update: Newron Pharmaceuticals reported receiving written FDA feedback about the clinical hold on enrollment at US sites in ENIGMA-TRS 2.
Safety information: The FDA said a fatal arrhythmic mechanism could not be definitively excluded after deaths were reported among participants receiving evenamide across clinical studies.
Trial status: The hold, imposed in April 2026, applies to US enrollment in ENIGMA-TRS 2; enrollment continues outside the US.
Key Findings:
Newron reported 4 deaths among evenamide-treated participants across clinical studies and 1 among placebo recipients. Investigators considered 3 deaths unrelated to treatment; 1 was considered possibly related because autopsy findings did not establish a definitive cause.
The FDA said a fatal arrhythmic mechanism could not be definitively excluded. Evenamide has also been associated with slight QTc shortening, for which the context reports no established risk or intervention threshold.
Newron reported mortality rates of 0.56% with evenamide and 0.27% with placebo; exposure-adjusted rates were 1.31 and 1.81 deaths per 100 patient-years, respectively.
The company said its safety database, including more than 10,000 ECGs from approximately 700 evenamide-treated participants, has not shown a consistent pattern of cardiac abnormalities or arrhythmias.
No US participants in ENIGMA-TRS 2 have received evenamide. The trial compares 15 mg twice daily with placebo over 12 weeks and plans to enroll at least 400 patients.
Interpretation:
The FDA’s concern remains unresolved, and US enrollment in ENIGMA-TRS 2 remains on hold. Newron is reviewing the feedback and considering additional cardiac screening and monitoring measures; it has not announced when US enrollment might resume.
Limitations:
The reported death counts and safety database findings are attributed to Newron’s account; the context does not provide independent FDA data.
The cause of the death considered possibly related was not definitively established.
The context does not provide detailed participant-level data or a definitive assessment of whether evenamide caused arrhythmias.
Conclusion:
ENIGMA-TRS 2 enrollment continues outside the US. Topline results from the separate ENIGMA-TRS 1 trial are expected in the first quarter of 2027.
