americanpharmaceuticalreviewMarch 08, 2021
Tag: Luvadaxistat , Neurocrine , interact , schizophrenia
Neurocrine Biosciences announced investigational drug luvadaxistat did not meet its primary endpoint in the Phase II INTERACT study in adults with negative symptoms of schizophrenia, as measured by the change from baseline on the PANSS NSFS at Day 84. Luvadaxistat met secondary endpoints of cognitive assessment, which merit further clinical evaluation. The adverse event profiles for luvadaxistat were consistent with previous trials. Takeda Pharmaceutical granted an exclusive license to Neurocrine Biosciences for seven pipeline programs, including luvadaxistat, in June 2020. The results from the Phase II INTERACT study are being evaluated to determine next steps for development activities.
"The Phase II INTERACT study was a well-designed and executed clinical study that resulted in a negative outcome for luvadaxistat on the primary endpoint assessing the change from baseline in negative symptoms of schizophrenia. We are, however, encouraged that secondary endpoints assessing cognitive performance within the trial were met and that treatment emergent adverse events reported were consistent with previous luvadaxistat studies," said Eiry W. Roberts, M.D., Chief Medical Officer of Neurocrine Biosciences. "The totality of the top-line data from this study therefore support further clinical evaluation of luvadaxistat. We plan to work with our partner Takeda as we move forward."
INTERACT is a Phase II, twelve-week, multi-center, randomized, double-blind, placebo-controlled, parallel-group study that evaluated the efficacy, safety, tolerability and pharmacokinetics of three dosing levels of investigational drug luvadaxistat as an adjunctive treatment of adult patients with negative symptoms of schizophrenia. Study enrollment began in January 2018 and included a total of 256 randomized patients.
Luvadaxistat is a potential first-in-class, investigational, oral, selective inhibitor with a high binding affinity to d-amino acid oxidase (DAAO). It targets glutamate, an abundant neurotransmitter in 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. The cortical disturbances account for the negative/cognitive symptoms of schizophrenia, while the downstream subcortical dopamine release manifests as the positive symptoms of the disorder.
Schizophrenia is a serious and complex syndrome with heterogeneous symptoms that impacts more than 20 million people worldwide. This chronic and disabling disorder is thought to result from a complex interplay of genetic and environmental risk factors. Schizophrenia is characterized by positive symptoms (e.g. hallucinations, delusions and disorganized thinking), negative symptoms [e.g., blunted affect, alogia (reduction in quantity of words spoken), avolition (reduced goal-directed activity due to decreased motivation), asociality, and anhedonia (reduced experience of pleasure)] and cognitive deficits. Annual associated costs for schizophrenia are estimated to be more than $150 billion in the United States.
Current schizophrenia medications include antipsychotics, which work primarily through antagonism of the dopamine D2 receptor. These approaches do not impact the negative symptoms of schizophrenia or cognitive impairment associated with schizophrenia (CIAS), suggesting that dysfunction of the dopamine system might not fully explain the negative and cognitive symptoms associated with schizophrenia. Animal, brain imaging, genetic, and postmortem brain studies have advanced our understanding of the underlying neurobiology of schizophrenia, with converging lines of evidence from these studies implicating NMDA receptor hypofunction in the pathophysiology of schizophrenia.
Contact Us
Tel: (+86) 400 610 1188
WhatsApp/Telegram/Wechat: +86 13621645194
Follow Us: