Newron's Phase III ENIGMA-TRS Program With Evenamide Approved for Treatment-resistant Schizophrenia

Newron Pharmaceuticals S.p.A., a biopharmaceutical company, has announced the regulatory approval for its pivotal ENIGMA-TRS Phase III development program. This program is aimed at evaluating evenamide as an add-on therapy for patients with treatment-resistant schizophrenia (TRS) who are currently on antipsychotics, including clozapine.

The ENIGMA-TRS Phase III program consists of two major studies known as ENIGMA-TRS 1 and ENIGMA-TRS 2. These studies are designed to meet the regulatory requirements outlined by the International Council for Harmonisation (ICH) for submitting an approval dossier for evenamide in significant markets such as the US and Europe.

ENIGMA-TRS 1 is an international study set to run for 52 weeks. It will be a randomized, double-blind, placebo-controlled Phase III trial that will investigate the efficacy, safety, and tolerability of evenamide at doses of 15mg BID and 30mg BID compared to a placebo. Patients enrolled in the study will be those already on second-generation anti-psychotics, including clozapine, and who meet the Treatment Response and Resistance Psychosis (TRRIP) international consensus criteria for TRS. The study plans to enroll at least 600 patients at research centers across Europe, Asia, Latin America, and Canada, with a 42-day screening period to confirm TRS diagnosis and other protocol criteria by an Independent Eligibility Assessment Committee (IEAC).

The key efficacy and safety assessments for ENIGMA-TRS 1 are scheduled to be conducted 12 weeks after randomization. However, the study will continue under double-blind, placebo-controlled conditions for a full year. Patient enrollment is expected to begin imminently, with the results from the 12-week assessment anticipated in the fourth quarter of 2026.

ENIGMA-TRS 2, approved by the FDA, will be conducted in the US and selected other countries, involving at least 400 patients. This study will also be a 12-week, randomized, double-blind, placebo-controlled Phase III trial focusing on the 15mg BID dose of evenamide. Like ENIGMA-TRS 1, it will involve selection criteria reviewed by the IEAC. The analysis of efficacy and safety will take place after 12 weeks. The start of this study is expected within the next three months at US investigational centers.

Dr. Stephen Marder of UCLA and Dr. Jean-Pierre Lindenmayer from the Nathan Kline Institute have expressed optimism about the potential of evenamide. They highlight its modulation of glutamate and selective action on sodium channels as promising mechanisms, especially for patients resistant to current antipsychotic medications.

The Chief Medical Officer of Newron, Dr. Ravi Anand, emphasized the regulatory approval of the ENIGMA-TRS trials as a milestone in the development of evenamide. He noted the enthusiasm of investigators about participating in this significant research program, driven by the positive outcomes seen in previous studies.

Evenamide's development targets patients with schizophrenia who show worsened psychosis on current therapeutic antipsychotics and those who are treatment-resistant, a group that represents a large portion of the global schizophrenia population. Previous studies have demonstrated evenamide's significant efficacy and safety as an add-on therapy, supporting the potential for a new therapeutic option for patients who do not benefit from existing antipsychotic treatments.

Newron has already entered licensing agreements with EA Pharma in Japan and Myung In Pharm in South Korea for the development and commercialization of evenamide in those regions. Newron continues to seek additional partnerships for the global development of evenamide.

Schizophrenia affects approximately 25 million people worldwide, with a substantial percentage of patients being treatment-resistant or poor responders to current antipsychotic medications. Evenamide, as the first new chemical entity with notable benefits in this challenging patient population, aims to fill the unmet medical need for effective treatments for TRS and poorly responding patients.