Plecanatide

Published

dm+d

Unassigned

New Medicines

TrulanceChronic idiopathic constipation

Information

Trulance
New molecular entity
Synergy Pharmaceuticals
Synergy Pharmaceuticals

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Launched
Mar 17: Launched for Constipation in USA under the brand name of Trulance

Jan 17. Approved in US


Jan 16: Filed in the US.


Jul 15: Synergy announced plans to file an NDA in January 2016


Jun 15: Synergy plans to file plecanatide for FDA approval using pooled data from 2 studies in Q4 2015


May 13: PIII programme to start 2H 2013

PII/III US study to start Oct 11


Jan 11: A PII/III study is planned to start 2Q 2011

Category

synthetic analogue of uroguanylin, a natriuretic hormone that regulates ion and fluid transport in the GI tract
The prevalence of GP-diagnosed constipation in the UK differs with age and ranges from 4 per 1000 in patients aged 18–29 years to 52 per 1000 in patients aged over 75.
Chronic idiopathic constipation
Oral

Trial or other data

Feb 17: Results of (NCT01982240) published in American Journal of Gastroenterology [16].


May 16: Synergy announces positive data from two phase III trials (n=2683) showing that treatment of chronic idiopathic constipation with plecanatide met the primary endpoint and demonstrated statistical significance in the proportion of patients who achieved a complete spontaneous bowel movement (p<0.004) [14]


Jul 15: Synergy announces positive top-line results from the pivotal PIII study (NCT02122471) evaluating the efficacy and safety of plecanatide 3mg and 6mg daily in 1337 adult pts with CIC. Both doses met the primary endpoint (proportion of durable overall responders) over 12 weeks vs. placebo. The durable response rate was 20% in patients taking 3mg and 6mg vs. 12.8% in placebo (p=0.004 for both doses vs. placebo). Both doses also showed statistically significant improvement for the secondary endpoint; Bristol Stool Form Scale (BSFS) scores compared to placebo (mean increase of 1.49 in 3mg and 1.5 in 6mg compared to 0.87 in placebo; p<0.001). Plecanatide was safe and well tolerated at both doses; the most common adverse event was diarrhoea. 20 pts (1.4%) in the trial experienced serious adverse events but there was no imbalance across treatment groups in either incidences or individual serious adverse events and discontinuations due to diarrhoea were infrequent [12]


Jun 15: Synergy announce PIII trial in more than 1,300 adults with CIC. Both doses of plecanatide significantly beat placebo in eliciting durable overall responses, which are defined by the FDA as at least three spontaneous bowel movements a week and a net increase of one bowel movement compared to baseline for 9 of the study´s 12 weeks. The durable response rate was 21% for patients taking 3 mg of Synergy´s drug and 19.5% for those getting twice that, each beating placebo´s 10.2%. Plecanatide also came through on its secondary endpoint of stool consistency, with each dose clocking a statistically significant improvement in Bristol Stool Form Scale scores compared to placebo. There was no imbalance of serious side effects between the three treatment groups, and rates of discontinuation were low for both plecanatide doses. Top-line data from a second study is expected in the next few weeks [11]


Mar 15: Three PIII studies are on-going but have completed recruitment. All are due to complete in 2015 [10]


Apr 14: NCT02122471 is a, randomized, 12-week, double-blind, placebo-controlled study to assess the safety and efficacy of plecanatide (3 and 6mg) in 1350 patients with chronic idiopathic constipation. The primary outcome is the proportion of patients who are overall responders ( defined as a weekly responder for at least 9 of the 12 treatment weeks, including at least 3 of the last 4 weeks. A weekly responder is defined as a patient who has ≥ 3 Complete Spontaneous Bowel Movements (CSBMs) per week and an increase from baseline of ≥1 CSBM for that week). The study starts Apr 14 and is due to complete Aug 15 [9]


Nov 13: The first of two planned PIII clinical trials in adult patients with chronic idiopathic constipation (CIC) has started. This pivotal trial is a randomised, double-blind RCT (n=1350)which compares a 12-week, dose-ranging regimen of plecanatide (3.0 and 6.0mg) against placebo in adult patients with CIC in the US and Canada. The primary endpoint of the study is the proportion of patients who are overall responders for the 12-week treatment period. [8]


Irritable bowel syndrome, constipation-predominant

Information

Licence extension / variation
Synergy Pharmaceuticals
Synergy Pharmaceuticals

Development and Regulatory status

None
None
Phase III Clinical Trials

Category

Synthetic analogue of uroguanylin, a natriuretic hormone that regulates ion and fluid transport in the GI tract.
IBS occurs in 10-20% of the population in the UK; approximately one third of patients have IBS with constipation (IBS-C) = loose stools 25% of the time [1].
Irritable bowel syndrome, constipation-predominant
Oral