After one patient death prompted an FDA hold this spring, Newron Pharmaceuticals has now shared that a total of four fatalities have been recorded among participants receiving its schizophrenia candidate. A fifth death was recorded among those taking the placebo.
Four deaths have occurred among patients receiving Newron Pharmaceuticals’ investigational schizophrenia drug, the biotech has revealed, three of which are considered unrelated to the asset.
In April, the FDA placed a hold on Newron’s Phase 3 ENIGMA-TRS 2 trial evaluating glutamate modulator evenamide as an adjunctive therapy for schizophrenia, barring further patient enrollment in the U.S. as the agency evaluated one patient death. The death occurred at a trial site abroad and was deemed unrelated to evenamide, Newron said at the time, though the hold remains in place.
The FDA cited concern about evenamide’s mode of action as a selective voltage-gated sodium channel blocker, according to a Thursday release from Newron. Certain sodium channel blockers may cause irregular heartbeats that can lead to serious cardiovascular events or seizures, the company noted.
Now, Newron has shared that four total deaths have occurred in patients receiving evenamide across all clinical studies to date, or an incidence of 0.56%—compared to one death among patients on placebo, or a 0.27% incidence.
Study investigators consider three of the four deaths in the investigational cohort unrelated to treatment, while one may be “possibly related” because a definitive cause of death was not determined after two autopsies.
Newron is reviewing the FDA’s feedback and all safety data across the development program, which includes more than 10,000 ECGs from about 700 patients receiving evenamide.
The Italian drugmaker said it hasn’t observed a pattern of cardiac abnormalities or arrhythmias in the preclinical and clinical safety data generated so far, which includes more than 5,000 ECGs from over 700 patients, according to the biopharma.
Newron is also assessing the addition of further cardiac screening and monitoring measures for the program, which includes the late-stage ENIGMA-TRS 1 and ENIGMA-TRS 2 trials. The former is an international, 52-week Phase 3 trial expected to enroll at least 600 patients across 20 countries by mid-October, while ENIGMA-TRS 2 is designed to be a 12-week study taking place in the U.S. and other select countries.
Given the FDA hold, no U.S. patients in ENIGMA-TRS 2 have received evenamide. Recruitment for the study continues outside the U.S.
“We remain confident in the ENIGMA-TRS studies and encouraged by the program’s progress,” Newron Chief Medical Officer Ravi Anand said in a prepared statement. “Our belief in the potential of evenamide and its novel mechanism for patients with treatment-resistant schizophrenia remains strong.” Patient safety is Newron’s “utmost priority,” Anand added.
The company’s stock was down slightly in pre-market trading. Newron’s leadership team is expected to provide a brief update about the program on Thursday at 9:30 a.m. ET.
