EA Pharma Co., a subsidiary of Eisai, has initiated a Phase III clinical trial in Japan for EA8001 (evenamide), a treatment for schizophrenia.
EA Pharma licensed the therapy from Newron Pharmaceuticals in a deal worth €117 million (approx. $136 million) in December 2024. The deal grants EA Pharma exclusive rights to develop, manufacture, and commercialize evenamide in Japan and several other Asian territories, including Brunei, Cambodia, Indonesia, Laos, Malaysia, Myanmar, the Philippines, Singapore, Thailand, and Vietnam. The company paid €44 million upfront, with additional payments tied to achieving specific development, regulatory, and commercial milestones.
The deal also included financial contributions from EA Pharma toward Newron’s upcoming global Phase III clinical studies conducted outside the licensed territories. Beyond these payments, Newron is entitled to receive tiered royalties on net sales, “reaching up to a double-digit percentage”. Newron retains rights in all other global markets, where it is concurrently conducting its own global Phase III program (ENIGMA-TRS) for treatment-resistant schizophrenia.
Clinical Trial Design
The study is a multicenter, randomized, double-blind, placebo-controlled trial. It will evaluate the efficacy, safety, and tolerability of evenamide as an add-on therapy in patients with treatment-resistant schizophrenia (TRS). These patients are characterized by a poor or inadequate response to at least two different types of existing antipsychotic medications. EA Pharma stated the trial aims to address the high unmet need in this difficult-to-treat patient population.
Evenamide, discovered by Newron Pharmaceuticals, is described as a novel excessive glutamate release modulator. This mechanism of action is distinct from current standard antipsychotics, which primarily work through dopamine and/or serotonin pathways. By modulating glutamate, the brain’s primary excitatory neurotransmitter, evenamide offers a potential new approach for patients who do not adequately respond to existing therapies, which can also be limited by side effects like weight gain and movement disorders, according to the company.
Earlier Clinical Data
The initiation of the Japanese Phase III trial follows encouraging clinical data. In a potentially pivotal international Phase II/III study (Study 008A), evenamide met its primary and key secondary endpoints. As an add-on to second-generation antipsychotics in 291 poorly responding chronic schizophrenia patients, evenamide met its primary and key secondary endpoints as an add-on therapy. Patients showed a statistically significant improvement of –16.6 points on the Positive and Negative Syndrome Scale (PANSS) total score compared to placebo. A significantly higher proportion of evenamide-treated patients (31.1%) achieved a “clinically meaningful benefit,” defined as at least a 20% PANSS improvement, versus 17.8% on placebo.
Critically, this benefit increased over time with continued treatment. Patients who rolled over into a one-year, open-label extension study achieved a mean PANSS reduction of 30.9 points from the original baseline. The study also reported that 89% of these long-term patients were rated “much improved” or “very much improved” on the Clinical Global Impression of Change (CGI-C) scale.
Regarding safety, evenamide exhibited a favorable profile. The research confirmed it was well-tolerated without causing the metabolic, weight gain, or movement disorder side effects commonly associated with current antipsychotics.
