Ironwood and Allergan Report Positive Topline Data from Phase IIIb Trial of LINZESS (linaclotide) in Adults with IBS-C
Ironwood Pharmaceuticals, Inc. and Allergan plc announced positive topline data from a Phase IIIb clinical trial evaluating LINZESS (linaclotide) 290 mcg on multiple abdominal symptoms in adult patients with IBS-C. The trial met its primary multi-component endpoint and demonstrated that linaclotide improved the overall abdominal symptoms of bloating, pain and discomfort in adult IBS-C patients compared to placebo. The trial also met both secondary endpoints. This trial was designed to highlight the impact of LINZESS on the overall abdominal symptoms of bloating, pain and discomfort, which are part of patients’ reported real-world experience, thereby enabling better communication about these symptoms.
LINZESS is marketed by Ironwood and Allergan in the United States and is indicated for the treatment of adults with IBS-C or chronic idiopathic constipation (CIC). Research has shown that approximately 95 percent of adults with IBS-C experience bothersome abdominal bloating, pain, and/or discomfort, with the majority experiencing these symptoms once a week or more. There are an estimated 13 million adults in the U.S. with IBS-C.1,2
“While research clearly suggests that the symptoms of abdominal bloating, pain, and discomfort have a considerable impact on adults suffering from IBS-C, in the clinical setting patients often use the word ‘constipation’ as a general term to represent their abdominal and bowel symptoms. This can lead to a less precise communication regarding their symptoms between patient and physician and can impact management,” said Lin Chang, M.D., Professor of Medicine at the Vatche and Tamar Manoukian Division of Digestive Diseases at the University of California, Los Angeles (UCLA). “I believe the data from this LINZESS Phase IIIb trial will be very important in helping patients and physicians have a more comprehensive dialogue about the multiple symptoms associated with IBS-C.”
Topline data from a randomized, double-blind, placebo-controlled Phase IIIb trial showed that linaclotide 290 mcg administered orally once daily demonstrated a statistically significant and clinically meaningful improvement in overall abdominal symptoms compared to placebo across the primary and both secondary endpoints. In the multi-component primary endpoint, linaclotide-treated patients showed a 29.7% mean decrease from baseline in their weekly abdominal score (bloating, pain and discomfort) through the 12-week treatment period, compared to 18.3% for the placebo-treated patients (p<0.0001). In the secondary endpoints, 40.5% of patients treated with linaclotide 290 mcg demonstrated a clinically meaningful response, as defined by the abdominal symptom score responder, compared to 23.4% of placebo-treated patients (p<0.0001). An abdominal symptom score responder was defined as a patient who experienced an improvement of at least two-points from baseline in their weekly abdominal score for at least six of 12 weeks of treatment period. These findings add to the significant body of data supporting the impact of linaclotide on the overall abdominal symptoms of bloating, pain and discomfort in adult IBS-C patients.
Linaclotide was well-tolerated in this Phase IIIb study, with the most commonly reported adverse event being diarrhea. During the treatment period, diarrhea was reported in 4.6% of patients on linaclotide 290 mcg as compared to 1.6% of patients on placebo. Study discontinuation resulting from diarrhea occurred in 1.6% of linaclotide 290 mcg patients compared to none of the placebo-treated patients.
“These topline results demonstrated that LINZESS can help provide overall relief of some of the multiple abdominal symptoms that IBS-C patients identify as among the most bothersome,” said Mike Shetzline, M.D., Ph.D., chief medical officer, senior vice president and head of drug development at Ironwood. “As the 10th Phase III trial of linaclotide to meet its primary endpoint, this study further contributes to the robust body of evidence supporting the use of LINZESS in adults with IBS-C and further strengthens its clinical profile.”
“IBS-C is a frustrating and uncomfortable condition, but it can be treated. We expect that communicating the full clinical profile of LINZESS on the overall abdominal symptoms of bloating, pain, and discomfort will broaden physicians’ understanding of the appropriate patient and may help those who need to find relief,” said David Nicholson, chief research & development officer at Allergan.
The randomized, double-blind, placebo-controlled, parallel-group study was designed to evaluate the efficacy and safety of LINZESS 290 mcg on multiple abdominal symptoms in adult patients with IBS-C. 614 patients were randomized to placebo or LINZESS 290 mcg once daily for 12 weeks, followed by a four-week randomized withdrawal period. The primary efficacy endpoint was change from baseline in abdominal score based on daily patient assessments of abdominal bloating, pain and discomfort at their worst, as reported on an 11-point numerical rating scale. Additional endpoints included change from baseline in spontaneous bowel movement frequency, complete spontaneous bowel movement frequency, stool consistency, and straining.
Additional data from this Phase IIIb trial are expected to be shared at upcoming scientific meetings and via peer-reviewed publications.