FDA advisers back Shire constipation drug

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Shire’s constipation drug prucalopride is moving closer to market – advisers to the FDA have just unanimously backed it as a treatment for chronic idiopathic constipation (CIC) in adults.

As is the case with all FDA committees, the recommendation by the Gastrointestinal Drugs Advisory Committee is not binding.

But the regulator will take the vote of the 10-person committee into consideration when it makes a final decision on the drug, due by December 21. It rarely goes against the recommendations of its expert advisers.

The committee also voted unanimously that the potential risk of cardiovascular adverse events with the use of prucalopride in adults with CIC had been addressed by Shire.

Prucalopride, a serotonin type 4 (5-HT4) receptor agonist, is a gastrointestinal prokinetic agent that stimulates colonic peristalsis, increasing bowel motility.

Drugs similar to prucalopride have been associated with adverse cardiovascular (CV) events in the past.

Novartis used to market a drug in this class for irritable bowel syndrome and constipation. But in 2007 the FDA asked Novartis to withdraw Zelnorm (tegaserod) from the market because of concerns about possible cardiovascular events.

A safety analysis found a higher chance of heart attack, stroke, and unstable angina in patients treated with Zelnorm compared with placebo, although the FDA later permitted restricted use in clinical trials.

But the FDA advisers said there were no such concerns with prucalopride after a review of data from five main phase III and one phase IV double-blind, placebo-controlled clinical trials.

The committee reviewed results from an observational, pharmacoepidemiology safety study that Shire sponsored to estimate the risk, as measured by the pooled adjusted incidence rate ratio (IRR), of major adverse CV events (MACE) in adult new users of prucalopride compared to adult new users of polyethylene glycol.

In the integrated efficacy analysis of the six main clinical trials, significantly more patients treated with prucalopride versus placebo achieved an average of three or more spontaneous, complete bowel movements (SCBMs) per week over the 12-week treatment period.

Andreas Busch, head of R&D at Shire, said: “We are pleased with the advisory committee’s vote today supporting prucalopride for the treatment of adults with chronic idiopathic constipation in the U.S., and will continue working with the FDA during the final stages of its review.”

Shire's $62 billion takeover by Takeda also appears to be on track to go ahead next year - Japan became the latest country to give antitrust clearance to the deal.

However the deal has not been approved by European regulators, who have until November 6 to make a decision.