The FDA has approved Linzess, the first oral therapy for pediatric functional constipation in patients aged 6 to 17 years, according to an agency release.
Previously approved for the treatment of adults with irritable bowel syndrome with constipation or chronic idiopathic constipation, the new drug application for Linzess (linaclotide 72 mcg, AbbVie/Ironwood) was assigned a Prescription Drug User Fee Act date of June 14, 2023 by the FDA — approximately 4 months earlier than the standard review cycle.
“Pediatric functional constipation is an all-too-common issue that physicians see every day, yet despite the tremendous distress it causes to our patients’ and their families, we haven’t had an FDA-approved prescription treatment to offer until now,” Jeffrey S. Hyams, MD, head of the Division of Digestive Diseases, Hepatology and Nutrition at Connecticut Children’s Medical Center, said in a press release. “The approval of Linzess for the treatment of functional constipation in pediatric patients ages 6-17 years old is a meaningful advancement for these young patients.”
The FDA based its decision on results from a 12-week double-blind, placebo-controlled, randomized, multicenter clinical trial among 426 patients aged 6 to 17 years old who were assigned to either linaclotide or placebo.
In the study, the Rome III diagnostic criteria for functional constipation was altered to include patients who had less than three spontaneous bowel movements (SBMs) per week. In addition, patients were required to exhibit one or more of the following criteria at least once per week for at least 2 months prior to the screening visit:
- History of stool withholding or excessive voluntary stool retention
- History of painful/hard bowel movements
- History of large diameter stools
- Presence of large fecal mass in rectum
- At least one episode of fecal incontinence
Additional efficacy data from prior well-controlled trials in adults with chronic idiopathic constipation were used to uphold the efficacy of linaclotide. The 12-week change from baseline in SBM frequency rate served as the study’s primary efficacy endpoint.
Results showed patients who received linaclotide compared with placebo achieved greater improvement in the average number of SBMs per week and SBM frequency improved during week 1 and was maintained through the 12-week treatment period.
“Today, Ironwood has broken new ground again in the history of Linzess, extending the clinical utility of our blockbuster treatment to 6-17-year-olds seeking relief for their debilitating [gastrointestinal] symptoms of functional constipation,” Tom McCourt, CEO for Ironwood Pharmaceutical, said in a release. “This approval is a momentous step forward in progressing our mission to advance the treatment of GI diseases and redefine the standard of care for GI patients, and in ushering in a new era of growth for our company.”
According to the FDA, diarrhea was the most reported adverse event following treatment with linaclotide. Patients should stop treatment with linaclotide if severe diarrhea occurs, the FDA warned. Additionally, linaclotide should not be administered to patients aged less than 2 years old or to any patient with known or suspected mechanical gastrointestinal obstructions.