Date: 2017-06-07
Type of information: Acceptation for review of a sNDA
Product name: Trulance™
Compound: plecanatide
Therapeutic area: Digestive diseases - Gastrointestinal diseases - Inflammatory diseases
Action mechanism: peptide/oral guanylate cyclase C agonist. Plecanatide is an analogue of uroguanylin, with the exception of a single amino acid. Uroguanylin is a naturally occurring and endogenous human GI peptide. Uroguanylin is thought to act in a pH-sensitive manner, targeting GC-C receptors primarily in the small intestine coinciding with areas of fluid secretion. Plecanatide activates these receptors found on the GI mucosal epithelial cells, leading to secretion of fluid, facilitating bowel movements.
Company: Synergy Pharmaceuticals (USA - NY)
Disease: chronic idiopathic constipation (CIC)
irritable bowel syndrome with constipation (IBS-C)
Latest news:
- • On June 7, 2017, Synergy Pharmaceuticals announced that the FDA has accepted for filing the company’s supplemental New Drug Application (sNDA) for Trulance™ (plecanatide) for the treatment of adults with irritable bowel syndrome with constipation (IBS-C). The Prescription Drug User Fee Act (PDUFA) date is January 24, 2018.
- The application is based on data from two randomized, 12-week, double-blind, placebo-controlled Phase 3 studies evaluating the efficacy and safety of Trulance™ for the treatment of adults with IBS-C. In these studies, Trulance™ 3 mg and 6 mg doses met the primary endpoint showing statistical significance in the percentage of patients who were Overall Responders compared to placebo during the 12-week treatment period (Study 1: 30.2% in 3 mg and 29.5% in 6 mg dose groups compared to 17.8% in placebo; p<0.001 for 3 mg and p<0.001 for 6 mg; Study 2: 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 ? 30% reduction in worst abdominal pain and an increase of ? 1 complete spontaneous bowel movement (CSBM) over baseline, in the same week, for at least 50% of the 12 treatment weeks. This is the current primary endpoint required for FDA approval in IBS-C.
- • On March 27, 2017, Synergy Pharmaceuticals announced that the company has submitted a supplemental New Drug Application (sNDA) for Trulance™ (plecanatide) for the treatment of adults with irritable bowel syndrome with constipation (IBS-C). The application is based on data from two randomized, 12-week, double-blind, placebo-controlled Phase 3 studies evaluating the efficacy and safety of Trulance™ for the treatment of adults with IBS-C. Across the two trials, more than 2,100 patients received a once-daily tablet of Trulance™ (3 mg or 6 mg doses) or placebo.
- Synergy announced positive results from the two Phase 3 trials of Trulance™ in adults with IBS-C in December 2016. In both trials, Trulance™ 3 mg and 6 mg doses met the primary endpoint showing statistical significance in the percentage of patients who were Overall Responders compared to placebo during the 12-week treatment period. (Study 1: 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; Study 2: 30.2% in 3 mg and 29.5% in 6 mg dose groups compared to 17.8% in placebo; p<0.001 for 3 mg and p<0.001 for 6 mg).
- In both studies, the most common adverse event was diarrhea (Study 1 = 3.2% at 3 mg and 3.7% at 6 mg compared to 1.3% at placebo; Study 2 = 5.4% at 3 mg and 4.3% at 6 mg compared to 0.6% at placebo).
- • On January 19, 2017, the FDA approved Trulance™(plecanatide) for the treatment of chronic idiopathic constipation (CIC) in adult patients. The drug, taken orally once daily, works locally in the upper GI tract to stimulate secretion of intestinal fluid and support regular bowel function. The safety and efficacy of Trulance™ were established in two 12-week, placebo-controlled trials including 1,775 adult participants. Participants were randomly assigned to receive a placebo or Trulance™, once daily. Participants in the trials were required to have been diagnosed with constipation at least six months prior to the study onset and to have less than three defecations per week in the previous three months, as well as other symptoms associated with constipation. Participants receiving Trulance were more likely to experience improvement in the frequency of complete spontaneous bowel movements than those receiving placebo, and also had improvements in stool frequency and consistency and straining.
- Trulance™ should not be used in children less than six years of age due to the risk of serious dehydration. Trulance™ should be avoided in patients six years of age to 18 years of age. The safety and effectiveness of Trulance have not been established in patients less than 18 years of age. Trulance should not be used in patients with known or suspected mechanical gastrointestinal obstruction.
- The most common and serious side effects of Trulance™ was diarrhea. Patients may experience severe diarrhea. If severe diarrhea occurs, patients should stop taking Trulance and contact their health care provider.
- • On July 15, 2016, Synergy Pharmaceuticals announced it has reached the FDA mid-cycle review milestone for the plecanatide new drug application (NDA) in chronic idiopathic constipation.
Patents:
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2017-01-19
UE authorization:
Favourable opinion UE:
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE:
OTC status:
Other news:
Is general: Yes
