FDA Flags Possible Safety Signal for Schizophrenia Candidate Evenamide After Four Trial Deaths
The FDA has identified a potential safety signal for the investigational schizophrenia drug evenamide after four deaths occurred among treated participants in clinical trials. U.S. enrollment in a phase III trial remains paused while Newron Pharmaceuticals reviews the agency's feedback, though studies continue in other countries. The concern centers on whether sodium channel blockade could cause dangerous heart rhythms, although investigators considered three of the four deaths unrelated to the drug.
Evenamide is an experimental glutamate modulator that acts by selectively blocking voltage-gated sodium channels in the brain. It is being tested as an add-on treatment for schizophrenia that has not responded to other therapies. The FDA's concern stems from the possibility that sodium channel blockade may provoke dangerous heart rhythms or seizures.
In April, U.S. enrollment in the phase III ENIGMA-TRS 2 study was paused after a participant died suddenly. That pause remains at American sites, while research continues elsewhere and new locations are being added. Among trial participants, four deaths occurred in those given evenamide and one in the placebo group; investigators judged three of the evenamide deaths unrelated, while one was deemed possibly related because autopsies found no definitive cause.
Count? First para: Evenamide(1) is2 an3 experimental4 glutamate5 modulator6 that7 acts8 by9 selectively10 blocking11 voltage-gated12 sodium13 channels14 in15 the16 brain17. It18 is19 being20 tested21 as22 an23 add-on24 treatment25 for26 schizophrenia27 that28 has29 not30 responded31 to32 other33 therapies34. The35 FDA's36 concern37 stems38 from39 the40 possibility41 that42 sodium43 channel44 blockade45 may46 provoke47 dangerous48 heart49 rhythms50 or51 seizures52. Second: In53 April,54 U.S.55 enrollment56 in57 the58 phase59 III60 ENIGMA-TRS61 2? Let's count "ENIGMA-TRS 2" maybe two tokens? Need under 120 total. It's around 110. Good. But "add-on" maybe hyphen. Fine. Need "a
... No extra. Need maybe blank line between sections? Fine. "EXPANDED:" and "CONTEXT:" labels. Need plain text. Ensure no markdown? It's plain. Good. Potential issue: "additional factual detail and background drawn ONLY from material above" We included "closely watched" maybe not in material? It says novel, maybe. "severe unmet need" not in material? Context can be analysis, not necessarily drawn only? Context is analysis. Expanded must only material. "closely watched" maybe not factual from material. In expanded, "investigational" from material. "add-on" from adjunctive. "treatment-resistant" from material. "dangerous heart rhythms or seizures" from material. "died suddenly" from sudden death. "new locations are added" from additional clinical sites being added. "Four evenamide-treated participants died, versus one in placebo group" from material. "investigators considered three unrelated and one possibly related because autopsies found no definitive cause." Good. "U.S. sites" from U