Luvadaxistat Fails to Improve Schizophrenia Cognition in Phase 2 Trial

Cognitive deficits represent a core clinical dimension of schizophrenia that strongly predicts a patient's functional trajectory and quality of life [1, 2]. While conventional antipsychotics effectively modulate dopamine pathways to manage psychosis, they offer minimal relief for the neurocognitive impairments that often persist despite symptomatic remission [3, 4]. This therapeutic ceiling has shifted research focus toward N-methyl-D-aspartate receptors (a type of glutamate receptor essential for synaptic plasticity and memory formation), which appear to be underactive in the schizophrenic brain [5, 6]. One targeted approach involves inhibiting D-amino acid oxidase (an enzyme responsible for degrading D-serine, a necessary co-agonist for glutamate receptor activation) to boost synaptic signaling [7, 8, 9]. Recent clinical investigations, such as the ERUDITE phase 2 trial of 203 adults, found that the selective inhibitor luvadaxistat failed to significantly improve Brief Assessment of Cognition in Schizophrenia (a standardized battery of cognitive tests) composite scores at doses of 20 mg (p = 0.75) or 50 mg (p = 0.69) [10]. Conversely, a 2025 meta-analysis of five trials involving 530 participants indicated that D-amino acid oxidase inhibitors as a class may still yield a standardized mean difference of 0.359 (p = 0.017) in cognitive function, suggesting that efficacy may vary significantly by specific compound or patient subgroup [7].