Disclosures: Chey reports serving as a consultant for Allergan, Alnylam, Arena, Biomerica, Ironwood Pharmaceuticals, IM Health, QOL Medical, Outpost, Ritter, Salix Pharmaceuticals, Takeda, and Urovant Sciences and received research grants from Biomerica, Ironwood Pharmaceuticals, Commonwealth Diagnostic International, QOL Medical, Salix, Urovant Sciences, Vibrant and Zespri.
February 18, 2021
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Delayed-release linaclotide improves abdominal pain in IBS-C

Disclosures: Chey reports serving as a consultant for Allergan, Alnylam, Arena, Biomerica, Ironwood Pharmaceuticals, IM Health, QOL Medical, Outpost, Ritter, Salix Pharmaceuticals, Takeda, and Urovant Sciences and received research grants from Biomerica, Ironwood Pharmaceuticals, Commonwealth Diagnostic International, QOL Medical, Salix, Urovant Sciences, Vibrant and Zespri.
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Patients with constipation-predominant irritable bowel syndrome treated with a delayed-release version of linaclotide experienced improvements in abdominal pain, according to study results.

William D. Chey, MD, from the University of Michigan, and colleagues wrote that linaclotide is currently used in an immediate-release formula in IBS-C to improve bowel transit. However, it also could have an application for abdominal pain.

“The hypersensitivity typical of IBS is likely complex and might be present throughout the GI tract; however, colonic sensory aerents appear key to the development and persistence of IBS-related abdominal pain,” they wrote. “Two delayed-release formulations of linaclotide are under development to target more distal regions of the GI tract, possibly leading to dierential eects on abdominal pain and bowel function.”

The first is delayed release 1 (DR1), which was designed to release the drug in the ileum. The second, called MD-7246, was designed to release linaclotide distally in the ileocecal junction and cecum, which could help relieve pain in the colon while minimizing secretory effects in the small bowel.

Researchers evaluated the safety, efficacy and dose response of the two delayed-release formulations in a phase 2b study comprising 532 patients with IBS-C. Investigators randomly assigned patients to placebo or one of seven once-daily linaclotide doses (DR1 30, 100, 300 g; MD-7246 30, 100, or 300 g; or immediate-release 290 g) for 12 weeks.

The key efficacy endpoints of the study were change from baseline in abdominal pain, complete spontaneous bowel movement frequency, and 6/12-week combined abdominal pain and constipation responder rate.

Chey and colleagues said that all patients who received all formulations of delayed-release linaclotide achieved greater improvements in abdominal pain from baseline compared with placebo throughout the treatment period. Patients who received DR1 and immediate-release linaclotide had greater improvements in complete spontaneous bowel movements frequency and higher combined responder rate compared with placebo.

Among patients who received DR1 and immediate-release, the most common adverse event was diarrhea. The frequency of diarrhea was generally lower among patients who received MD-7246 and placebo.

“MD-7246 maintained improvement in abdominal pain relief relative to placebo with little impact on bowel symptoms and very low rates of treatment-associated diarrhea,” Chey and colleagues wrote. “MD-7246 should, therefore, be examined as an option for treating IBS-related abdominal pain without altering bowel habits. Further MD-7246 studies across the spectrum of IBS subtypes, including those with diarrhea predominance, should be considered based on these observations.”