Two Phase III trials of plecanatide meet endpoint in chronic idiopathic constipation- Synergy Pharmaceuticals

Synergy Pharmaceuticals has announced positive top-line results from the first of two pivotal Phase III clinical trials evaluating the efficacy and safety of two different plecanatide treatment doses (3.0 mg and 6.0 mg), taken as a tablet once-a-day, in 1,346 adult patients with chronic idiopathic constipation (CIC). Preliminary analysis of the data indicates that both plecanatide 3.0 mg and 6.0 mg doses met the study�s primary endpoint and demonstrated statistical significance in the proportion of patients in the intention-to-treat population who were durable overall responders compared to placebo during the 12-week treatment period (21.0% in 3.0 mg and 19.5% in 6.0 mg dose groups compared to 10.2% in placebo; p<0.001 for both doses.>

The durable overall responder endpoint is the current FDA endpoint required for US approval in CIC. Plecanatide would be the first drug approved for CIC using the more stringent regulatory requirement for durability in the response. Notably, plecanatide was safe and well tolerated at both doses; the most common adverse event was diarrhea, which occurred in 5.9% of patients in 3.0 mg and 5.5% of patients in 6.0 mg dose groups compared to 1.3% of placebo-treated patients.

Stool consistency was the key secondary endpoint reported with top-line analyses; both 3.0 mg and 6.0 mg plecanatide doses showed statistically significant improvement from baseline in Bristol Stool Form Scale (BSFS) scores compared to placebo (mean increase of 1.53 in 3.0 mg and 1.52 in 6.0 mg dose groups compared to a mean increase of 0.77 in placebo;). 15 patients in the trial (1.1%) experienced serious adverse events but there was no imbalance across treatment groups in either incidences or individual serious adverse events. Synergy plans to announce top-line data results from the second phase 3 CIC trial with plecanatide in the first half of 3Q 2015. The company plans to file its first new drug application (NDA) with plecanatide in the CIC indication in the fourth quarter of this year.

Comment: Synergy will be competing with the first in the GC-C agonist class � Ironwood Pharmaceuticals and Forest Laboratories' ( now Allergan') Linzess (linaclotide), which was approved in August 2012 as a once-daily treatment for IBS-C or CIC .