Plecanatide effective for treating IBS-linked constipation

Last Updated: 2018-04-13

By Will Boggs MD

NEW YORK (Reuters Health) - Plecanatide relieves abdominal pain and constipation in patients with irritable bowel syndrome with constipation (IBS-C), according to results from two randomized trials.

"Plecanatide should be considered a first-line agent in the treatment of IBS-C," Dr. Darren M. Brenner from Northwestern University-Feinberg School of Medicine, in Chicago, told Reuters Health by email. "It improves a global array of symptoms quickly and efficiently with a minimal side-effect profile and high tolerance. This is not surprising given that it is such a close analog of human uroguanylin."

Plecanatide is approved in the U.S. for treatment of adults with chronic idiopathic constipation and adults with IBS-C.

By activating guanylate cyclase-C (GC-C) receptors in the intestinal epithelium, plecanatide, like uroguanylin, increases secretion of fluid into the intestinal lumen, thereby hydrating stools.

Dr. Brenner and colleagues evaluated the efficacy and safety of once-daily doses of plecanatide (3 and 6 mg) in two identical 12-week, placebo-controlled phase 3 trials of 2,189 adults with IBS-C.

The percentage of overall responders - defined as patients who experienced both a 30% or greater reduction in worst abdominal pain and an increase of at least one complete spontaneous bowel movement per week for at least six of the 12 treatment weeks - was significantly greater with plecanatide than with placebo in study 1 (30.2% with plecanatide 3 mg, 29.5% with plecanatide 6 mg and 17.8% with placebo) and in study 2 (21.5%, 24.0% and 14.2%, respectively).

Both doses of plecanatide were also associated with significantly greater percentages of sustained-efficacy responders (overall responder plus weekly response for at least two of the last four weeks), greater mean improvements from baseline in stool consistency and greater improvements from baseline in straining.

At week 12, significantly more plecanatide-treated patients were satisfied with treatment and indicated they would continue treatment, the researchers report in The American Journal of Gastroenterology, online March 15.

Diarrhea was the only adverse event occurring in at least 2% of patients and at an incidence rate greater than placebo: 4.3% with 3 mg plecanatide, 4.0% with 6 mg plecanatide and 1.0% with placebo.

"Physicians and practitioners continue to use an array of over-the-counter medications to treat this patient population, but in reality, these medications are only effective for either inducing laxation or mild pain relief," Dr. Brenner said. "Patients tell us anecdotally and in clinical trials that they want treatments which improve their pain and bowel issues at the same time. A medication like plecanatide with can improve both sets of symptoms concurrently."

Dr. Apoorva Chandar from Cleveland Clinic, in Ohio, who has reviewed the effect of linaclotide, which selectively activates GC-C receptors, in IBS-C patients, told Reuters Health by email, "Right now, it is too premature to say that plecanatide will be the next big IBS-C drug. When linaclotide was introduced 5 years ago, it became an overnight hit because there was nothing like it at that time. And linaclotide has been studied well enough now and people know it well enough."

"It is great that a new GC-C drug is available, but I would wait until there's more data from head-to-head trials and more data on quality of life," he said. "The plecanatide trials don't provide much data on quality of life other than treatment satisfaction (which isn't the same as improvement in quality of life). So, I would wait until more extensive data are published."

"When 2 or more drugs of the same class are available in the market, the only good way to knowing how they compare against each other is by conducting a real-world, pragmatic head-to-head randomized controlled trial," Dr. Chandar said. "This should also incorporate aspects of costs of treatment and costs of treating adverse events. Only then can we really say that one drug is better than the other. Until we have more conclusive data, the choice of what drug to choose for IBS-C will boil down to costs, patient values and preferences, patient demographics, and adverse events experienced."

Synergy Pharmaceuticals Inc. funded the two trials and had various financial ties to most of the authors, including Dr. Brenner.

SOURCE: https://bit.ly/2vazAoh

Am J Gastroenterol 2018.