tl;dr: 4 Tote mit Evenamide vs 1 Toter mit Placebo. Bei einem der 4 konnte die Todesursache nicht geklärt werden. Unklar ist nun, ob Evenamide verantwortlich für Herzrhythmus-Störungen sein könnte. Hier der relevante Teil der Adhoc:
FDA Clinical Hold and ENIGMA-TRS Program Update
The FDA’s concern relates to the known risk that certain members of the class of sodium channel blockers may trigger arrhythmias which in turn can lead to serious cardiovascular events or seizures. Evenamide is a glutamate modulator via its action as a selective voltage-gated sodium channel blocker.
In its written communication, the FDA notes four deaths among patients treated with evenamide across all clinical studies with evenamide to date, compared with one death among patients receiving placebo. Of the four deaths among patients receiving evenamide, three were considered unrelated to evenamide by the study investigators, while one was considered “possibly related” because two autopsies could not identify a definitive cause of death. The four deaths have been characterized by the FDA as a potential safety signal based on the possibility of a fatal arrhythmic mechanism, which cannot be definitively excluded through post hoc adjudication. Evenamide is also known to result in 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. Newron has not observed a pattern of cardiac abnormalities or arrhythmias in the preclinical and clinical safety data generated with evenamide to date. This includes 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.