Linaclotide found to benefit patients aged 6-17 with functional constipation

Positive Topline Data of benefits of linaclotide in Functional Constipation in pediatric Patients Aged 6-17 with Functional Constipation have been reported in Phase III Trial.

"Functional constipation is one of the most common gastrointestinal complaints in pediatric patients, one that significantly impacts young patients' lives. Despite its high prevalence, FC remains challenging to treat because there are no FDA approved prescription treatments for children," said Jeffrey S. Hyams, MD, Head, Division of Digestive Diseases, Hepatology, and Nutrition, Connecticut Children's Medical Center, Professor of Pediatrics, University of Connecticut School of Medicine.

"These strong data further our understanding of the safety profile of linaclotide in pediatric patients aged 6-17 with FC and demonstrate evidence of its potential to provide therapeutic benefit to these patients suffering from FC."

In this study, a total of 330 patients were randomized in a 1:1 ratio between linaclotide or placebo. Topline data indicate that linaclotide showed a statistically significant and clinically meaningful improvement compared to placebo in 12-week SBM frequency rate (SBMs/week), the primary endpoint. Linaclotide-treated patients demonstrated a greater than two-fold least squares mean change from baseline in SBMs/week (2.220) compared to placebo (1.050) (p<0.0001).

Stool consistency, as assessed by Bristol Stool Form Scale (BSFS) scores, which was the secondary endpoint, also showed an improvement at weeks 12 with linaclotide compared to placebo. The least squares mean change from baseline at week 12 was 1.108 and 0.685 points, respectively (p=0.0001). The BSFS is a 7-point scale ranging from 1 (separate hard, difficult-to-pass lumps) to 7 (liquid stools).

Overall, linaclotide (72 mcg) was well tolerated. The most frequently reported treatment-emergent adverse event was diarrhea, which occurred in 4.3% of linaclotide-treated participants versus 1.8% in the placebo group.

"We are excited by the results of this Phase III trial and are focused on identifying an expeditious regulatory path forward, with our partner AbbVie, to support delivering this potential first functional constipation therapeutic to pediatric patients ages 6-17 in need," said Mike Shetzline, M.D., Ph.D., chief medical officer, senior vice president and head of research and drug development at Ironwood Pharmaceuticals.

"Our vision for LINZESS has always been simple but powerful-keep patients at the center of everything we do," said Tom McCourt, chief executive officer at Ironwood Pharmaceuticals. "We have seen the positive impacts that LINZESS has had with more than 4 million unique patients with IBS-C or chronic idiopathic constipation (CIC) treated since launch in 2012, and our team now looks forward to potentially expanding its clinical utility to the treatment of functional constipation in an underserved population."

These data are from the FC cohort of the Phase III, multicenter, randomized, double-blind, parallel-group, safety, and efficacy study of linaclotide vs. placebo in children ages 6-17 years with FC. Participants in the FC cohort must have fulfilled modified Rome III Criteria for child/adolescent FC.

Ironwood expects to share these Phase III trial data at upcoming scientific meetings and via peer-reviewed publications.

LINZESS is developed and marketed by Ironwood and AbbVie in the United States and is indicated for the treatment of adults with IBS-C or CIC. It is not approved for use in patients less than 18 years of age.

Reference:

Robin, Samantha G. et al., Prevalence of Pediatric Functional Gastrointestinal Disorders Utilizing the Rome IV Criteria, The Journal of Pediatrics, December 2017