Profile of plecanatide in the treatment of chronic idiopathic constipation: design, development, and place in therapy

Abstract

Constipation is a multifactorial disorder that can cause significant psychological distress to patients and economic burden on the health care system. Many patients are not satisfied with their current established treatment, highlighting the need for new and improved therapeutic options. Guanylate cyclase-C (GC-C)/cyclic guanosine monophosphate agonists have emerged as a safe and efficacious class of drugs for the treatment of chronic idiopathic constipation (CIC). Plecanatide, a second-in-class, US FDA-approved, synthetic GC-C agonist, has recently been approved in the US for the treatment of irritable bowel syndrome with constipation at doses of 3 and 6 mg and CIC at the 3 mg dosage. In this study, we summarize the design of this novel 16-amino acid uroguanylin analog, drug development through Phase I, II, and III clinical studies, and its role in the treatment of CIC.

Keywords:

• plecanatide
• uroguanylin
• constipation

Acknowledgments

The authors thank Ms. Helen Smith and Kimberly Donaldson for secretarial support.

Author contributions

AS contributed to manuscript concept and design, critical revision, and final approval; AAH contributed to manuscript preparation; JB contributed to manuscript preparation; and SSCR contributed to manuscript concept and design, critical revision, and final approval. All authors contributed to data analysis, drafting and revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

AS has served as an advisory board member for Ironwood and Synergy Pharmaceuticals. SSCR has served as an advisory board member and received research grant support from Forest Laboratories, Ironwood Pharmaceuticals, and Synergy Pharmaceuticals. The authors report no other conflicts of interest in this work.