New clinical study: CeNeRx BioPharma's CXB722 has potential as novel anxiolytic

CeNeRx BioPharma, Inc., a clinical stage company developing and commercializing innovative treatments for diseases of the central nervous system, today reported that a new clinical study shows that its investigational compound CXB722 has potential as a novel anxiolytic, demonstrating a significant effect on both endocrine and cardiovascular biomarkers associated with stress.  CXB722 and its prodrug Ayrene (CXB724) are hypothalamic-pituitary-adrenal (HPA) axis modulators for the treatment of a variety of CNS disorders including anxiety and depression.

CXB722 has been studied in approximately 800 patients, demonstrating safety and efficacy in a range of mood and anxiety disorders.  Unlike traditional anxiolytic drugs such as benzodiazepines, CXB722 has demonstrated no impairment of motor performance in either preclinical or clinical studies.  Results from this most recent study provide important insight on how CXB722 lowers key stress hormones associated with chronic anxiety and other mood disorders.

This new study, presented at a recent neuroscience meeting, was designed to assess the effects of CXB722 on HPA axis-related responses to psychosocial stress.  In the study, 24 healthy volunteers participated in a Trier Social Stress Test (TSST) experiment, a well-validated approach to measuring changes in physiologic and endocrine endpoints in response to acute psychosocial stress.  Approximately half of the subjects received CXB722 and half received a placebo for seven days prior to participating in stress-inducing activities, such as a mock job interview.  Neuroendocrine markers that typically rise in response to stressful situations were measured before and after exposure to these activities.  While the placebo group exhibited the expected elevations in plasma cortisol, salivary cortisol and plasma ACTH, these biomarkers were significantly attenuated in the subjects randomized to receive CXB722.  In addition, an analysis of continuous pulse rate data demonstrated an attenuation of heart rate elevation in the CXB722 group compared to the placebo group.  Consistent with the large existing clinical database, CXB722 was safe and well-tolerated, with no drop-outs due to an adverse event.

"The results of the Trier Social Stress Test are consistent with the large preclinical and clinical database previously assembled for CXB722, which indicated that this unique mechanism compound has promise as a potential treatment for anxiety and other mood disorders without the limiting side effects of many current therapies," said Dr. Daniel Burch, Executive Vice President of R&D and Chief Medical Officer of CeNeRx.  "We are encouraged by these positive findings that set the stage for further development of Ayrene, our prodrug that fully converts to CXB722 in plasma and offers potential pharmacokinetic advantages compared to its parent compound."

The ability of CXB722 to modulate stress-related neuroendocrine activity evidenced in this study highlights its unique mechanism of action.  Preclinical studies show that CXB722 may modulate corticotrophin-releasing factor (CRF)-containing neurons associated with activation of the HPA axis.  These results add to the growing clinical database that supports the role of this novel mechanism in a range of mood and anxiety disorders, without the performance limitations associated with traditional anxiolytics such as benzodiazepines.  Potential applications may include prevention of post-traumatic stress disorder and treatment of social anxiety disorder.