Newron Pharmaceuticals has received regulatory approval to advance its pivotal Phase III development program, ENIGMA-TRS, which will evaluate Evenamide as an add-on therapy for patients with treatment-resistant schizophrenia (TRS). The program, comprising two studies, aims to fulfill requirements for marketing authorization in major global markets including the United States and Europe.
Patient recruitment for the trials is commencing immediately, with results anticipated in late 2026. This development represents a significant milestone for the Switzerland-based biopharmaceutical company in addressing a critical unmet medical need in schizophrenia treatment.
Promising Clinical Evidence Supports Phase III Program
The advancement to Phase III follows compelling data from earlier clinical studies. In January 2024, Newron reported final one-year results from study 014/015, a Phase II open-label trial evaluating Evenamide as an add-on therapy to a single antipsychotic in TRS patients. The data demonstrated sustained, clinically significant benefits that increased throughout the one-year treatment period.
More than 70% of patients experienced a clinically important reduction in disease severity, with 25% achieving "remission" – the highest level of improvement possible in schizophrenia patients and unprecedented in the TRS population. Remarkably, approximately 50% of patients who completed one year of treatment no longer met the criteria used to diagnose treatment resistance, and no patients relapsed during the treatment period.
"The positive evenamide data and strong momentum from our partnering agreements have set the stage for our pivotal Phase III randomized, double-blind, one-year trial," said Stefan Weber, CEO of Newron. The upcoming study will compare evenamide to placebo as an add-on treatment in at least 600 patients with TRS.
Novel Mechanism of Action Addresses Treatment Gap
Evenamide represents a potential breakthrough as the first glutamate modulator for schizophrenia treatment. This novel mechanism of action differentiates it from current antipsychotics on the market, potentially offering new hope for patients who respond inadequately to existing therapies.
In April 2024, Newron announced positive results from study 008A, a potentially pivotal four-week, randomized, double-blind and placebo-controlled Phase III study of Evenamide as an add-on therapy in patients with chronic schizophrenia demonstrating inadequate benefit from their current second-generation antipsychotic. The study met its primary endpoint (improvement of the Positive and Negative Syndrome Scale PANSS Total Score) and key secondary endpoint (improvement of the Clinical Global Impression of Severity CGI-S), with a 96% study completion rate.
Further analysis revealed significant multi-domain benefits, with improvements continuing to increase up to day 29, suggesting potentially larger and more enduring effects with long-term treatment. The compound has consistently demonstrated a favorable safety and tolerability profile across studies.
Strategic Partnerships Expand Global Reach
Newron has secured important licensing agreements to support Evenamide's global development and commercialization. The company signed development and commercialization agreements with EA Pharma (a subsidiary of Eisai) for Japan and other Asian territories in December 2024, and with Myung In Pharm for South Korea in January 2025.
These partnerships have significantly strengthened Newron's financial position. The company reported a net profit of EUR 15.8 million in 2024, compared with a net loss of EUR 16.2 million in 2023, largely due to license income of EUR 44.5 million predominantly resulting from the upfront payment under the EA Pharma/Eisai agreement.
Treatment-Resistant Schizophrenia: A Significant Unmet Need
Treatment-resistant schizophrenia affects approximately 30% of schizophrenia patients, who show minimal improvement despite adequate trials of at least two different antipsychotic medications. These patients experience persistent positive symptoms (hallucinations, delusions), negative symptoms (reduced emotional expression, avolition), and cognitive impairment, leading to significant disability and healthcare burden.
Current treatment options for TRS are limited, with clozapine being the only approved medication specifically for this indication. However, clozapine is associated with serious side effects including agranulocytosis, which requires regular blood monitoring, and many patients still do not achieve adequate symptom control.
Financial Outlook and Future Plans
Newron's total available cash resources, along with proceeds from the two licensing agreements for Evenamide, are expected to fund the company's planned development programs and operations through 2026. The company is also pursuing further development opportunities for Evenamide beyond the existing licensing agreements.
"A key objective for 2025 will also be strengthening our institutional shareholder base, and the preparation of a potential registration of our shares in the USA, the key capital market for our industry," Weber noted.
Newron has a proven track record in bringing CNS therapies to market. Its Parkinson's disease treatment, Xadago® (safinamide), is approved in over 20 markets, including the USA, UK, EU, Switzerland, and Japan, and commercialized in partnerships with Zambon and Meiji Seika.
Looking Forward: Potential Impact on Schizophrenia Treatment
If successful in Phase III trials and subsequently approved, Evenamide could represent a paradigm shift in the treatment of TRS. As the first add-on therapy specifically developed for this difficult-to-treat population, it could offer new hope to patients who currently have few effective treatment options.
The glutamatergic inhibition mechanism of action offers an innovative therapeutic approach distinct from traditional dopamine-focused antipsychotics, potentially addressing different aspects of the complex pathophysiology of schizophrenia.
With patient recruitment now underway for the pivotal Phase III program, the next few years will be critical in determining whether Evenamide can fulfill its promise as a breakthrough therapy for one of psychiatry's most challenging conditions.
