Type of information: Acceptation for review of a NDA
Product name: Resolor® - SHP555
Therapeutic area: Digestive diseases - Gastrointestinal diseases - Inflammatory diseases
- 5-HT4 receptor agonist. Prucalopride is a selective, high-affinity 5-HT4 receptor agonist with gastrointestinal prokinetic effects. It binds to and stimulates 5-HT4 receptors, which are involved in the stimulation of high-amplitude propagated contractions (HAPCs) and co-ordination of bowel motility. In an integrated analysis of six large randomised controlled clinical trials including males and females, it was shown that more than 1 in 4 adult patients experienced normal bowel function (average of ?3 SCBMs per week over 12 weeks) with Resolor. This was more than twice that of placebo.
Company: Shire (UK - USA)
- symptomatic treatment of chronic constipation in patients whom laxatives fail to provide adequate relief
- chronic idiopathic constipation
- • On March 5, 2018 , Shire announced that the FDA has accepted the submission of a New Drug Application (NDA) for prucalopride (also known as SHP555). Prucalopride is being evaluated as a potential once-daily treatment option for chronic idiopathic constipation (CIC) in adults. The FDA is expected to provide a decision on or around December 21, 2018, the designated Prescription Drug User Fee Act (PDUFA) action date with FDA noting that timelines are flexible and subject to change based on workload and identification of potential review issues.
- Prucalopride has been studied in more than 90 clinical trials worldwide over the last 20 years, including five main Phase 3 and one Phase 4 double-blind, placebo-controlled clinical trials that informed the NDA submission. An integrated analysis of the six, main randomized, controlled clinical trials evaluated the global efficacy and safety of prucalopride 2 mg daily in men and women with chronic constipation; study designs across the trials were similar. Overall, there were 2,484 adult patients included in the integrated efficacy analysis and 2,552 adult patients included in the integrated safety analysis; all patients included received prucalopride ?2 mg/day or placebo. Significantly more patients treated with prucalopride versus placebo (27.8% vs 13.2%; p<0.001) achieved an average of three or more spontaneous, complete bowel movements (SCBMs) per week over the 12-week treatment period. The most common (?5%) treatment-emergent adverse events (TEAEs) in the prucalopride group were gastrointestinal disorders (nausea, diarrhea, and abdominal pain) and headache. The proportion of patients who experienced any adverse cardiovascular (CV) events were comparable between groups (1.8% for placebo vs. 2.0% for prucalopride). Serious TEAEs were reported in 1.6% of patients who received prucalopride vs 2.4% of patients who received placebo. No fatal TEAEs occurred.9
- Shire conducted an observational, pharmacoepidemiology safety study to estimate, in real-world settings, the risk of major adverse cardiovascular events (MACE) in patients treated with prucalopride compared to patients treated with polyethylene glycol (PEG). Drugs similar to prucalopride have been associated with adverse cardiovascular events in the past. Study results are included in the NDA to provide the FDA additional understanding of the CV safety profile of prucalopride.
- • On June 3, 2015, Shire announced that Resolor® (prucalopride) has been approved by the European Commission for use in adults for the symptomatic treatment of chronic constipation in whom laxatives fail to provide adequate relief. Resolor® is approved for use in women in Europe, so the new variation extends the use of this treatment to male patients. The efficacy, safety and tolerability of Resolor® in male patients with chronic constipation were evaluated in a 12-week, multicentre, randomised, double-blind, placebo-controlled study (N=370). The data showed that a statistically significantly higher percentage of subjects in the Resolor® group (37.9%) experienced normal bowel function, as assessed by an average of ?3 spontaneous complete bowel movements (SCBMs) per week, compared with subjects in the placebo treatment group (17.7%) (p<0.0001) over the 12-week treatment period. The most common adverse events associated with Resolor® were headache and gastrointestinal disorders. The safety profile of Resolor was consistent with that seen in studies of female patients. Resolor® was first approved in Europe in 2009 for the symptomatic treatment of chronic constipation in women in whom laxatives fail to provide adequate relief.
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
UE authorization: 2009-10-15/2015-05-29
Favourable opinion UE:
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: