FDA approves Linzess as first treatment for pediatric functional constipation
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The FDA has approved Linzess, the first therapy for pediatric functional constipation in patients aged 6 to 17 years, according to an agency release.
The supplemental new drug application for Linzess (linaclotide 72 µcg, AbbVie/Ironwood), which was previously approved for the treatment of adults with irritable bowel syndrome with constipation or chronic idiopathic constipation, was assigned an early Prescription Drug User Fee Act date of June 14, approximately 4 months earlier than would be assigned in 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 an Ironwood Pharmaceuticals press release. “The approval of Linzess for the treatment of functional constipation in pediatric patients ages 6 to 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 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; and
- 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 company 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.
- Reference:
- Ironwood Pharmaceuticals announces FDA approval of new indication for Linzess (linaclotide) for the treatment of functional constipation in pediatric patients ages 6-17 years-old. https://investor.ironwoodpharma.com/press-releases/press-release-details/2023/Ironwood-Pharmaceuticals-Announces-FDA-Approval-of-New-Indication-for-LINZESS-linaclotide-for-the-Treatment-of-Functional-Constipation-in-Pediatric-Patients-Ages-6-17-Years-Old/default.aspx?_gl=1*4isjmd*_ga*MTI5MTY0NzUyNi4xNjg2NjE2MzQ3*_ga_39QZELPZ60*MTY4NjY1MjM0OS4zLjEuMTY4NjY1MjM1My4wLjAuMA..&_ga=2.45869484.988370594.1686616348-1291647526.1686616347. Published June 12, 2023. Accessed June 12, 2023.
Perspective
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Ben Freiberg, MD
Constipation is a common occurrence in both adult and pediatric populations. It is estimated that up to 30% of children struggle with constipation, with the vast majority being functional constipation with no underlying disease or disorder. Rather, the changes in bowel movements are due to a combination of factors, including diet (decreased fiber and fluid intake) and behavior (withholding due to pain or changes in daily schedule) along with the colon’s ability to store increasingly more stool.
As with other conditions that affect children, medications are often used off-label to treat constipation, meaning that prescribers will use them beyond what is written in the package insert. This in no way should imply improper, illegal or contraindicated use by the practitioner. It is often the case that certain populations, particularly children, are not included in studies or that there is not a large enough sample size to determine the safety and efficacy in that population when submitting for FDA approval.
This approval confirms what is already known among pediatric gastroenterologists: There are many medications, including linaclotide, that are beneficial in treating functional constipation in children. This will hopefully open the door for other clinical trials to include pediatric patients and allow these medications to be covered by insurance.
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