Positive results have been reported from the first of two pivotal phase 3 trials evaluating the efficacy and safety of plecanatide (Synergy Pharmaceuticals), an investigational once-daily, orally administered compound, in adults with irritable bowel syndrome with constipation (IBS-C).
A preliminary analysis of the data has indicated that both doses of plecanatide (3 mg and 6 mg) met the study’s primary endpoint, showing statistical significance in the percentage of patients who were overall responders compared with placebo during the 12-week treatment period (21.5% in the 3-mg group and 24.0% in the 6-mg group compared with 14.2% in the placebo group; P = 0.009 for 3 mg and P < 0.001 for 6 mg). An overall responder, as defined by the FDA, is a patient who fulfills both a 30% or greater reduction in worst abdominal pain and an increase of one or more complete spontaneous bowel movements from baseline in the same week for at least 50% of the 12 treatment weeks.
The most common adverse event was diarrhea, which occurred in 3.2% and 3.7% of patients in the 3-mg and 6-mg groups, respectively, compared with 1.3% of placebo-treated patients.
Overall, the rates of withdrawal from treatment because of an adverse event were low (1.9% and 1.8% in the 3-mg and 6-mg groups, respectively, compared with 0% in the placebo group), and discontinuations due to diarrhea were infrequent (0.8% and 1.6% versus 0%).
Plecanatide is a peptide made up of 16 amino acids. With the exception of a single amino acid substitution, it is identical to uroguanylin. Plecanatide is the first investigational drug designed to replicate the function of uroguanylin, a naturally occurring and endogenous human gastrointestinal peptide that acts in a pH-sensitive manner to target receptors located primarily in the proximal small intestine. Plecanatide stimulates fluid secretion and promotes the stool consistency necessary to support normal bowel function.
Plecanatide is currently under FDA review for the treatment of chronic idiopathic constipation, with a target action date of January 29, 2017. Synergy Pharmaceuticals plans to file a supplemental new drug application for the use of plecanatide in patients with IBS-C in the first quarter of 2017.
Source: Synergy Pharmaceuticals; December 9, 2016.