FDA Approves Prucalopride for Chronic Idiopathic Constipation

The US Food and Drug Administration (FDA) has approved Shire’s prucalopride (Motegrity) for the treatment of chronic idiopathic constipation (CIC).

Prucalopride is a selective serotonin-4 (5-HT₄) receptor agonist that is administered as a once-daily, oral treatment. By enhancing colonic peristalsis to increase bowel motility, it offers a different class of treatment for CIC.

“The approval of prucalopride marks a new day in the treatment of CIC,” Howard Mayer, MD, senior vice president and chief medical officer of Shire, said in a recent statement. “This significant milestone reinforces our continued commitment to the GI community and advances our goal of addressing the unmet need of patients suffering from rare, specialized and common GI conditions.”

Previously in March 2018, the FDA accepted a new drug application for prucalopride for the same indication.

Six double-blind, placebo-controlled, randomized, multicenter clinical studies lasting 12 weeks (studies 1-5) or 24 weeks (study 6) evaluated the efficacy of once-daily treatment with prucalopride. Most of the 2,484 patients were female (76%) and Caucasian (76%) and had an average age of 47 (+/- 16 years).

Across 5 of 6 trials, the primary endpoint was achieved significantly by more patients administered prucalopride (an average of ≥3 complete spontaneous bowel movements [CSBMs] per week over 12 weeks, considered normalization of BM frequency) compared to those in the placebo group (19%-38% prucalopride ≤2 mg vs. 10%-20% placebo).

As early as week 1, rapid responses were observed in the patients administered prucalopride, and improvements maintained throughout 12 weeks of treatment.

The FDA has requested that 5 post-marketing studies be conducted in order to assess the pharmacokinetics, efficacy, and safety of prucalopride in pediatric patients with CIC (6 months old to less than 18 years of age) and pregnant and lactating women with CIC treated with prucalopride.

Dyspnea, rash, pruritus, urticaria, and facial edema are treatment reactions that have been observed. Prucalopride is contraindicated in patients with a history of hypersensitivity to prucalopride and “in patients with intestinal perforation or obstruction due to structural or functional disorder of the gut wall, obstructive ileus, severe inflammatory conditions of the intestinal tract such as Crohn’s disease, ulcerative colitis, and toxic megacolon/megarectum.”

Headache, abdominal pain, nausea, diarrhea, abdominal distension, dizziness, vomiting, flatulence, and fatigue include the most common adverse reactions (≥2%). While discontinuation of prucalopride due to adverse events was low (5% prucalopride 2 mg once daily; 3% placebo), reported adverse events included diarrhea or headache, which typically resolved within a few days.

“As a gastroenterologist, it’s important for me to help patients with CIC find a treatment that works well for them,” said Brooks Cash, MD, chief of the Division of Gastroenterology, Hepatology, and Nutrition at the University of Texas Health Science Center at Houston. “It’s exciting to be able to now offer my patients a new treatment option that addresses colonic peristalsis.”