Development

FDA keeps Newron’s ENIGMA-TRS 2 study on clinical hold

FDA keeps Newron’s ENIGMA-TRS 2 study on clinical hold

Italy-based Newron Pharmaceuticals (SIX: NWRN, XETRA: NP5) said the US FDA’s clinical hold on new patient enrollment at US sites in the Phase III ENIGMA-TRS 2 study of evenamide remains in place, while enrollment continues to expand across Europe, Asia, and Latin America.

Why it matters: The decision prolongs uncertainty around the US portion of evenamide’s pivotal program just days after Newron said a September 22 Type A meeting with the FDA had been constructive and that it expected US enrollment to resume in the near future. The broader Phase III program remains active, with ENIGMA-TRS 1 unaffected and due to read out in Q1 2027.

The hold was imposed on April 29, 2026 after Newron notified the FDA of the sudden unexpected death of a study participant at a site outside the US. The investigator assessed the event as unrelated to study treatment, and an independent international safety monitoring board recommended that the studies continue as designed. No US patients had received evenamide; patients at US sites had only entered screening.

Newron said it is awaiting written communication from the FDA setting out the basis for maintaining the hold and any further protocol changes required before US enrollment can resume.

ENIGMA-TRS 2 is a 12-week, randomized, double-blind, placebo-controlled Phase III study evaluating evenamide 15 mg twice daily as add-on therapy in patients with treatment-resistant schizophrenia. Around 80 patients have entered screening against a target enrollment of at least 400.

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The parallel ENIGMA-TRS 1 study is unaffected by the hold and is expected to enroll at least 600 patients by mid-October 2026. Newron plans to report topline data from the 12-week primary endpoint in Q1 2027.

Evenamide is a voltage-gated sodium-channel modulator designed to reduce excessive glutamate release as add-on therapy to existing antipsychotics. In the earlier 291-patient 008A study, evenamide reduced PANSS scores by 10.2 points at Day 29 versus 7.6 points with placebo.


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