Sparks - Newron Pharmaceuticals

Newron has provided further clarity on the FDA clinical hold affecting US recruitment in its Phase III ENIGMA-TRS 2 study of evenamide for treatment-resistant schizophrenia (TRS). The company has noted that FDA has raised concerns over a potential cardiac safety signal, citing four deaths among evenamide-treated patients versus one on placebo. Of the four deaths, three were considered unrelated to evenamide by investigators, while one was classified as possibly related, as a definitive cause of death could not be established. However, Newron has highlighted the absence of a consistent pattern of cardiac abnormalities across more than 10,000 electrocardiograms from c 700 evenamide-treated subjects. Notably, exposure-adjusted mortality was lower with evenamide (1.31 vs 1.81 per 100 patient-years for placebo), although a potential arrhythmic mechanism cannot be definitively excluded.

While the broader ENIGMA-TRS programme continues to progress, we view the update as introducing some regulatory uncertainty around ENIGMA-TRS 2 timelines. ENIGMA-TRS 1 remains on schedule, with pivotal 12-week data expected in Q127, while ENIGMA-TRS 2 recruitment continues outside the US with additional sites expected to be onboarded, including in Europe. However, the timing of US recruitment resumption remains unclear. While we expect a positive ENIGMA-TRS 1 readout to strengthen evenamide’s efficacy proposition, resolving the FDA’s safety concerns remains critical, with prolonged delays potentially affecting regulatory submission and commercialisation timelines. Our existing estimates already incorporate a degree of conservatism, assuming a 2029 commercial launch.