Shire announces FDA approval of Motegrity for treatment of CIC

Shire announced that the FDA has approved Motegrity, a once-daily, oral treatment option for adults with Chronic Idiopathic Constipation, or CIC. Motegrity, a selective serotonin-4, or 5-HT4, receptor agonist, provides a different class of treatment for CIC that works by enhancing colonic peristalsis to increase bowel motility. Motegrity is expected to launch in 2019 in the United States, where an estimated 35M adults are living with CIC. While not all patients may be right for treatment, Motegrity represents a new option. The efficacy of once-daily treatment with Motegrity was evaluated in six double-blind, placebo-controlled, randomized, multicenter clinical studies lasting 12 weeks or 24 weeks. Of the 2,484 patients, most were female and caucasian, with an average age of 47. During studies, significantly more patients taking Motegrity achieved the primary endpoint than those in the placebo group across five of six trials. A rapid response was seen with Motegrity as early as week 1, with improvements maintained throughout 12 weeks of treatment. The FDA has requested that Shire conduct five post-marketing studies evaluating the pharmacokinetics, efficacy and safety of Motegrity in pediatric patients with CIC and pregnant and lactating women with CIC treated with Motegrity. Motegrity is contraindicated in patients with a history of hypersensitivity to Motegrity. Reactions include dyspnea, rash, pruritus, urticaria and facial edema have been observed. Motegrity is also contraindicated 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. In clinical trials, suicides, suicide attempts, and suicidal ideation have been reported. A causal association between treatment with Motegrity and an increased risk of suicidal ideation and behavior has not been established. Most common adverse reactions are headache, abdominal pain, nausea, diarrhea, abdominal distension, dizziness, vomiting, flatulence and fatigue. Overall, discontinuation due to adverse events was low. If reported, adverse events of diarrhea or headache typically resolved within a few days. In addition, cardiovascular safety was evaluated in a MACE analysis of the double-blind, placebo-controlled and open-label studies. It was also assessed in a retrospective observational study, which demonstrated no increase in the risk of MACE with Motegrity relative to polyethylene glycol.

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