Recent advances in the understanding of basic neuroenteric mechanisms, and the role of effectors and transmitters in the brain-gut axis have provided opportunities to develop new therapeutic agents for irritable bowel syndrome (IBS).
Furthermore, human pharmacodynamic studies utilizing transit, colonic, or rectal sensitivity and brain imaging have been useful in determining therapeutic efficacy.
Drs Michael Camilleri and Lin Chang from Minnesota, USA provide an overview of medications that have not yet been approved for treatment of patients with irritable bowel syndrome yet have shown promise in phase 2B trials.
|The changing regulatory approval process has impacted the development of IBS drugs.|
These include drugs that act on the serotonin receptor and transporter system.
The drugs examined by the team included antidepressants, norepinephrine reuptake inhibitors, and opioids.
In addition, cholecystokinin antagonists, neurokinin-antagonists, chloride channel activators, guanylate cyclase C agonists, atypical benzodiazepines, probiotics, and antibiotics were considered.
The researchers reported that the changing landscape in the regulatory approval process has impacted the development of irritable bowel syndrome drugs.
Guidance documents from regulatory agencies in Europe and the United States have focused on patients' reported outcomes and associated quality of life.
After a decade of experience with different endpoints, some data has been generated on psychometric validation and unprecedented information about responsiveness of the binary or global endpoints to drug therapy.
The team emphasize the necessity to pursue further validation studies before or during pivotal phase 2B or 3 trials.
Dr Camilleri and colleague conclude, “The hope of providing relief to patients should galvanize all parties to achieve these goals.”