Neurocrine Biosciences has announced that its ERUDITE™ Phase 2 clinical study of investigational compound luvadaxistat (NBI-1065844) failed to meet its primary endpoint as a potential treatment to improve cognitive impairment in patients with schizophrenia.
Luvadaxistat failed to replicate the cognitive endpoints data seen in the earlier INTERACT™ study. Researchers say this was due in part to the large variability seen in the cognitive measures across the population studied and a potential imbalance in the baseline characteristics of subjects enrolled across the treatment arms.
In the INTERACT study, 50 mg luvadaxistat resulted in a statistically significant improvement in measure of cognition on the Brief Assessment of Cognition in Schizophrenia (BACS) and cognitive performance on the Schizophrenia Cognition Rating Scale (SCoRS).
The INTERACT study represented the first time statistical significance had been demonstrated for both cognitive measure and function within a single study.
“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,” said Eiry W. Roberts, M.D., Chief Medical Officer.
“We therefore plan to halt further development of luvadaxistat at this time and instead will focus our efforts and resources on the advancement into Phase 3 clinical development of NBI-1117568 for schizophrenia and NBI-1065845 for major depressive disorder.
“We are excited by the opportunity that lies ahead of us to bring forward potential medicines for patients in these important areas of unmet need in neuropsychiatry.”
Luvadaxistat (NBI-1065844) is an investigational, oral, selective inhibitor with a high binding affinity to d-amino acid oxidase (DAAO), which metabolizes D-Serine, a primary NMDA receptor co-agonist in the limbic region of the brain.
In schizophrenia, N-methyl D-aspartate (NMDA) receptor hypofunction on PV+ gamma-aminobutyric acid (GABA) interneurons results in disinhibition of cortical or hippocampal glutamate neurons projecting to the pyramidal neurons, which are associated with cognitive impairment seen in schizophrenia.
The ERUDITE™ Phase 2 clinical study is a randomised, double-blind, placebo-controlled, parallel group study to evaluate the efficacy safety and tolerability of luvadaxistat in adults with cognitive impairment associated with schizophrenia (CIAS). For more information about this study, visit ClinicalTrials.gov.
