Newron reported a constructive FDA Type A meeting for its Phase III ENIGMA-TRS 2 trial of evenamide in treatment-resistant schizophrenia, outlining protocol changes aimed at resolving the U.S. enrollment hold.
Written by: Mr Rishabha Sonawane, BPharm
Reviewed By: Pharmacally Editorial Team
Newron Pharmaceuticals has reported a constructive outcome from a face-to-face Type A meeting with the U.S. Food and Drug Administration (FDA), outlining a regulatory pathway to address the agency’s concerns and support the potential resumption of new patient enrollment at U.S. sites participating in the Phase III ENIGMA-TRS 2 study (NCT07184619) of evenamide for treatment-resistant schizophrenia (TRS). The company plans to submit protocol amendments developed following discussions with the FDA as the next step toward resolving the enrollment hold.
The meeting follows the FDA’s April 29, 2026 decision to place a clinical hold on new patient enrollment at U.S. sites participating in the ENIGMA-TRS 2 trial. Although the clinical hold remains in effect pending the FDA’s review of the proposed protocol amendments, the agency’s feedback outlines the next regulatory steps for the U.S. clinical program.
Global Phase III Program Continues to Advance
During the face-to-face meeting, Newron and the FDA discussed potential actions to resolve the issues underlying the enrollment hold. The company thanked the FDA for the opportunity to discuss the outstanding issues and said the collaborative dialogue is expected to help expedite their resolution while advancing the pathway toward resuming patient enrollment in the United States.
Evenamide is Newron’s lead investigational add-on therapy for treatment-resistant schizophrenia (TRS), intended for patients with persistent symptoms despite standard antipsychotic treatment. Earlier studies demonstrated progressively improving efficacy with a favourable safety and tolerability profile, supporting advancement into Phase III development.
The global ENIGMA-TRS Phase III program includes two randomised, double-blind, placebo-controlled studies. ENIGMA-TRS 1 is enrolling at least 600 patients across 15 countries in Europe, Asia, Latin America, and Canada to evaluate evenamide 15 mg and 30 mg twice daily alongside background second-generation antipsychotics, including clozapine. Patient enrollment continues across participating international sites. The primary endpoint is change from baseline in Positive and Negative Syndrome Scale (PANSS) scores at 12 weeks, with primary efficacy and safety results expected in the fourth quarter of 2026.
ENIGMA-TRS 2, launched in the United States in December 2025 following FDA and Institutional Review Board approvals, is evaluating evenamide 15 mg twice daily in at least 400 patients across U.S. and selected international sites. Although enrollment at U.S. sites remains paused under the FDA clinical hold, the proposed protocol amendments are intended to support resumption following FDA review.
Mechanism of Action
Evenamide is a first-in-class glutamate modulator designed to regulate excessive glutamate release, representing a novel approach beyond conventional dopamine-targeting antipsychotics. By addressing glutamatergic dysfunction, the investigational therapy aims to provide a differentiated treatment option for patients with persistent symptoms despite existing therapies.
Commercial Partnerships
Newron has established regional commercialisation partnerships for evenamide, including EA Pharma, an Eisai subsidiary, in Japan and selected Asian territories, while Myung In Pharm holds commercialisation rights in South Korea, supporting future market access if the investigational therapy receives regulatory approval.
The company also markets Xadago® (safinamide) for Parkinson’s disease. The therapy is approved in multiple global markets, including the United States, European Union, United Kingdom, Japan, Canada, Australia, South Korea, and Latin America. It is commercialised by Zambon globally, with Supernus Pharmaceuticals holding U.S. rights and Meiji Seika Pharma responsible for Japan and other Asian markets.
Next Regulatory Steps
The FDA’s review of the proposed protocol amendments will determine when enrollment can resume at U.S. ENIGMA-TRS 2 sites. Meanwhile, ENIGMA-TRS 1 continues enrolling internationally, with fourth-quarter 2026 efficacy and safety data representing the next major clinical milestone. Newron noted that regulatory review, enrollment, and clinical development remain subject to inherent uncertainties.
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About the Writer
Rishabha Sonawane, B.Pharm (LinkedIn) is healthcare writer with a strong interest in medical writing, regulatory affairs, clinical research, and AI-driven drug discovery. He has completed specialized training from the NIH and ICMR in clinical pharmacology, clinical research, and scientific writing. Passionate about evidence-based healthcare communication, he focuses on translating complex scientific research into clear, accurate, and engaging medical content.