Synergy Pharmaceuticals Inc. announces Phase III data for plecanatide to treat irritable bowel syndrome with constipation.

Synergy Pharmaceuticals Inc. announced positive top-line results from the first of two pivotal phase III clinical trials evaluating the efficacy and safety of plecanatide, an investigational once-daily orally-administered compound, in 1,135 adult patients with irritable bowel syndrome with constipation (IBS-C).

Preliminary analysis of the data indicates that both plecanatide 3 mg and 6 mg doses met the study�s primary endpoint and showed statistical significance in the percentage of patients who were Overall Responders compared to placebo during the 12-week treatment period (21.5% in 3 mg and 24.0% in 6 mg dose groups compared to 14.2% in placebo; 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 greater than 30% reduction in worst abdominal pain and an increase of more than 1 complete spontaneous bowel movement (csbm) 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% of patients in 3 mg and 3.7% of patients in 6 mg dose groups compared to 1.3% of placebo-treated patients.our patients in the trial (0.4%) experienced serious adverse events but there was no imbalance across treatment groups in either incidences or individual serious adverse events.>

Overall, the rates of withdrawal from treatment because of an adverse event were low (1.9% in 3 mg and 1.8% in 6 mg dose groups compared to 0 in placebo) and discontinuations due to diarrhea were infrequent (0.8% in 3 mg and 1.6% in 6 mg dose groups compared to 0 in placebo).

Comment:Top-line data for plecanatide in irritable bowel syndrome with constipation (IBS-C) from the first of two pivotal Phase III trials appears to be confirmation that the guanylyl cyclase C receptor agonist will have the advantage of less incidence of diarrhea than its chief rival, Astellas Pharma Inc./Ironwood Pharmaceuticals Inc.�s Linzess.

Comment:There was also less incidence of diarrhea versus Linzess (linaclotide), also a GCC agonist, in the Phase III program for plecanatide in chronic idiopathic constipation (CIC), its lead indication. Plecanatide is under review at FDA for CIC with an action date of 29 January 2017.