Challenges to the Therapeutic Pipeline for Irritable Bowel Syndrome

End Points and Regulatory Hurdles

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Recent advances in our 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 (particularly for drugs that act on motor function). This review provides an overview of medications that have not yet been approved for treatment of patients with IBS yet have shown promise in phase IIB trials. These include drugs that act on the serotonin receptor and transporter system: antidepressants, norepinephrine reuptake inhibitors, opioids, cholecystokinin antagonists, neurokinin-antagonists, chloride channel activators, guanylate cyclase C agonists, atypical benzodiazepines, probiotics, and antibiotics. The changing landscape in the regulatory approval process has impacted the development of IBS 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 end points that have generated some data on psychometric validation and unprecedented information about responsiveness of the binary or global end points to drug therapy, it is necessary to pursue further validation studies before or during pivotal phase IIB or III trials. The hope of providing relief to patients should galvanize all parties to achieve these goals.

Original languageEnglish (US)
Pages (from-to)1877-1891
Number of pages15
JournalGastroenterology
Volume135
Issue number6
DOIs
StatePublished - Dec 2008

Fingerprint

Irritable Bowel Syndrome
Hope
Pharmaceutical Preparations
Serotonin Plasma Membrane Transport Proteins
Narcotic Antagonists
Validation Studies
Guanylate Cyclase
Serotonin Receptors
Cholecystokinin
Probiotics
Benzodiazepines
Psychometrics
Neuroimaging
Antidepressive Agents
Norepinephrine
Therapeutics
Quality of Life
Anti-Bacterial Agents
Drug Therapy
Brain

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Challenges to the Therapeutic Pipeline for Irritable Bowel Syndrome : End Points and Regulatory Hurdles. / Camilleri, Michael; Chang, Lin.

In: Gastroenterology, Vol. 135, No. 6, 12.2008, p. 1877-1891.

Research output: Contribution to journalArticle

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