Plecanatide meets primary endpoint in second phase 3 trial in IBS-C

Plecanatide improved abdominal pain and constipation in patients with constipation-predominant irritable bowel syndrome in the second of two phase 3 clinical trials, the manufacturer announced.

Plecanatide (Synergy Pharmaceuticals) is an oral peptide under investigation for IBS-C, which is composed of 16 amino acids designed to replicate the function of the natural human GI peptide uroguanylin, which targets GC-C receptors mainly in the proximal small intestine, and thus stimulates fluid secretion and promotes stool consistency, according to a press release.

“We are understandably very pleased with these results, and how well the data support the first pivotal phase 3 IBS-C trial which we announced recently,” Gary S. Jacob, PhD, chairman and CEO of Synergy Pharmaceuticals, said in the press release. “The successful phase 3 trials are a major step in our mission to better serve patients, as we believe plecanatide has the potential to be an important new treatment option for the millions of people suffering from IBS-C.”

As part of the phase 3 plecanatide clinical program, which was performed in North America and will support the company’s regulatory submission in the U.S., this second trial randomly assigned 1,054 IBS-C patients (76.4% women) to receive 3 mg or 6 mg plecanatide or placebo once daily for 12 weeks.

The percentage of overall responders — defined by the FDA as patients who have at least a 30% reduction in worst abdominal pain and an increase of at least one complete spontaneous bowel movement from baseline, during the same week for at least half of the 12 treatment weeks — served as the primary endpoint. Preliminary analysis showed both doses of plecanatide met the primary endpoint, with 30.2% of the 3 mg group, 29.5% of the 6 mg group vs. 17.8% of the placebo group (both P < .001).

Diarrhea was the most common adverse event, occurring in 5.4%, 4.3% and 0.6% of the groups, respectively. Serious adverse events occurred in ten patients, and these were comparable across treatment groups. In addition, 2.6%, 2.3% and 0.8%, respectively, withdrew from treatment due to an adverse event, and 1.7%, 1.2% and 0% withdrew due to diarrhea, respectively.

The company expects to share additional data at an upcoming scientific meeting, according to the press release.

Plecanatide is also under review by the FDA for chronic idiopathic constipation, with a Prescription Drug User Fee Act (PDUFA) target action date of January 29, 2017. If approved, the company also plans to file a New Drug Application Supplement with Clinical Data (sNDA) for plecanatide in IBS-C in the first quarter of 2017.

Disclosures: Jacob is employed by Synergy Pharmaceuticals.