Neurocrine Biosciences has announced that its Phase II ERUDITE clinical trial of luvadaxistat (NBI-1065844) did not meet its primary endpoint of improving cognitive impairment in patients with schizophrenia. The randomized, double-blind, placebo-controlled trial enrolled adults with cognitive impairment associated with schizophrenia (CIAS) to assess the safety, efficacy, and tolerability of luvadaxistat.
The ERUDITE study's failure to replicate the cognitive endpoint data observed in the earlier INTERACT study has led Neurocrine to halt further development of luvadaxistat. According to Neurocrine, variability in cognitive measures across the study population and potential imbalances in baseline characteristics of enrolled subjects contributed to the disappointing outcome.
Luvadaxistat Mechanism and Previous Findings
Luvadaxistat is an investigational, oral, selective inhibitor targeting d-amino acid oxidase (DAAO), designed to modulate NMDA receptor function in the brain. The NMDA receptor plays a crucial role in cognitive processes, and its dysfunction has been implicated in the cognitive deficits observed in schizophrenia. Neurocrine acquired the rights to develop and commercialize luvadaxistat from Takeda Pharmaceutical.
In the INTERACT study, a 50 mg dose of luvadaxistat demonstrated a statistically significant improvement in cognition, as measured by the Brief Assessment of Cognition in Schizophrenia (BACS) and cognitive performance on the Schizophrenia Cognition Rating Scale (SCoRS). Neurocrine highlighted that the INTERACT study was the first to demonstrate statistical significance for both cognitive measure and function within a single study.
Strategic Shift for Neurocrine
Eiry Roberts, M.D., Chief Medical Officer of Neurocrine Biosciences, expressed disappointment with the ERUDITE results but emphasized the company's commitment to addressing unmet needs in neuropsychiatry. "While it’s disappointing that luvadaxistat did not meet the primary endpoint in this study, we understand the challenges and hurdles that exist in identifying potential medicines for the treatment of cognitive impairment in schizophrenia," Roberts stated.
Neurocrine plans to focus its resources on advancing NBI-1117568 into Phase III clinical development for schizophrenia and NBI-1065845 into Phase III for major depressive disorder. The company reported positive top-line results from its Phase II clinical study of NBI-1117568 in August, an investigational oral treatment for schizophrenia.
Schizophrenia and Cognitive Impairment
Schizophrenia is a chronic and disabling mental health condition affecting over 20 million people worldwide, according to the World Health Organization. In the United States, the annual costs associated with schizophrenia are estimated to exceed $150 billion. Cognitive impairment is a common feature of schizophrenia, affecting approximately 80% of individuals with the disorder, and significantly impacts daily functioning and quality of life.
