Synergy reports positive top-line results from plecanatide phase 2b study in patients with IBS-C

Synergy Pharmaceuticals Inc. (NASDAQ:SGYP) today announced positive top-line results from a phase 2b dose-ranging study assessing plecanatide's safety and efficacy in 424 patients with irritable bowel syndrome with constipation (IBS-C). The primary objective of this trial was to determine an effective, safe and well tolerated dose for plecanatide phase 3 trials with IBS-C patients. Synergy is pleased to report this trial has achieved that objective. Preliminary analysis of the data indicates that plecanatide demonstrated statistically significant improvement in complete spontaneous bowel movement (CSBM) frequency - the study's primary endpoint - and was safe and well tolerated. Notably, patients taking the plecanatide 3.0mg dose experienced statistically significant improvement in change from baseline versus placebo in worst abdominal pain and met the FDA overall responder endpoint for IBS-C over the 12-week treatment. An overall responder for the FDA endpoint fulfills both ≥30% reduction in worst abdominal pain and an increase of ≥1 complete spontaneous bowel movements (CSBMs) from baseline in the same week for at least 50% of the weeks (i.e. 6/12 weeks).

"We are very pleased to see a consistent response at the 3.0mg plecanatide dose for statistical improvement in CSBM frequency with a less than 10% diarrhea rate for treating both CIC and IBS-C indications," said Dr. Gary S. Jacob, CEO and Chairman of Synergy Pharmaceuticals. "In addition, the 3.0mg dose has now demonstrated a statistically significant improvement for worst abdominal pain as well as the overall responder FDA endpoint for IBS-C. We believe this is the ideal dose for normalizing bowel movements and treating the symptoms of both CIC and IBS-C patients with a more favorable tolerability profile that's suitable for chronic use. We plan to immediately move forward with plecanatide in IBS-C patients at the 3.0mg dose and expect to initiate our phase 3 trials in the second half of this year."

"IBS-C is a complex disorder associated with both chronic constipation and abdominal pain symptoms that are unique to each patient," said Dr. Philip B. Miner, President and Medical Director of the Oklahoma Foundation for Digestive Research. "There is a significant medical need among patients and physicians for more treatment options that are effective, safe and well tolerated for chronic, everyday use. I am encouraged by the data observed in this trial as plecanatide has demonstrated efficacy and a favorable tolerability profile for treating IBS-C patients."

The plecanatide 3.0mg dose was selected for phase 3 based on achieving statistically significant improvement in the study's primary endpoint and key secondary endpoints assessed in the topline analyses, which included change from baseline versus placebo over 12 weeks in: CSBM frequency (1.29 placebo vs. 2.74,>

Plecanatide was safe and well tolerated with no treatment-related serious adverse events. The most common event was diarrhea, which occurred in 9.3 percent of the 3.0mg plecanatide-treated patients.

At this time the company has reviewed only top-line results and further analyses will be conducted in the coming weeks. Once full analysis of the data is complete, Synergy plans to present the results of the trial at an appropriate scientific conference.

The company intends to initiate pivotal phase 3 trials in IBS-C patients in the second half of 2014.

IBS-C Phase 2b Study

This was a randomized, 12-week, double-blind, placebo-controlled, dose-ranging study to assess the safety and efficacy of plecanatide in patients with IBS-C. The study evaluated the effects of 0.3, 1.0, 3.0 or 9.0 mg plecanatide or placebo administered orally once daily to adults meeting Rome III criteria for IBS-C. In addition, patients were required to meet the criteria for the IBS-C subtype, which is further characterized by stool pattern, such that ≥ 25% of defecations are hard or lump stools and ≤ 25% of defecations are loose or watery stools. During pre-treatment at baseline, patients are required to have at least 3 days in each week with pain scores ≥ 3 on a 0 to 10 scale.

Participants underwent two-week-baseline, 12-week-treatment, and two-week-post treatment evaluations with daily assessments of bowel habits and symptom severity using an interactive voice response system. The primary efficacy endpoint was the change from baseline in the mean number of CSBMs over the 12-week treatment period. Key secondary endpoints were: (1) abdominal pain and (2) stool consistency. Abdominal pain intensity was measured on an 11-point severity scale (0 to 10) and stool consistency using the Bristol Stool Form Scale (BSFS). An overall responder for the FDA endpoint fulfills both ≥30% reduction in worst abdominal pain and an increase of ≥1 complete spontaneous bowel movements (CSBMs) from baseline in the same week for at least 50% of the weeks (i.e. 6/12 weeks).