FDA expands label for Ironwood/AbbVie’s Linzess to youngest pediatric FC patients

Ironwood Pharmaceuticals (Nasdaq: IRWD) has received US FDA approval to extend the use of Linzess (linaclotide) to children as young as two years of age with functional constipation (FC), lowering the approved age threshold from six years and reinforcing the drug’s position as the only prescription therapy cleared for pediatric FC in the US. The agency granted priority review for the application, which was co-developed with AbbVie.

Linzess 72 mcg is approved as a once-daily oral therapy for pediatric FC in patients aged two years and older. The formulation can be administered by opening the capsule and mixing its contents with applesauce or water, a practical consideration for younger children who cannot swallow capsules. The drug carries a boxed warning contraindicating use in patients under two years of age, based on nonclinical data in neonatal mice showing deaths from dehydration following a single clinically relevant dose, an effect attributed to age-dependent elevated guanylate cyclase-C (GC-C) expression. Linzess is also contraindicated in patients with known or suspected mechanical gastrointestinal obstruction.

The expanded indication was supported by a 12-week Phase III randomized, placebo-controlled trial in pediatric patients aged two to five years with FC. The primary endpoint assessed spontaneous bowel movement frequency, and Linzess 72 mcg demonstrated improvement over placebo.

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Linaclotide is a locally acting peptide agonist of the GC-C receptor on intestinal epithelial cells. Receptor activation elevates intracellular cyclic GMP, promoting fluid secretion into the intestinal lumen and accelerating transit.

Linzess remains the only FDA-approved prescription therapy specifically indicated for pediatric FC, a position it has held since its initial approval in this population covering patients aged six years and older. The label extension to ages two to five fills a gap in a patient group where clinicians have historically relied on osmotic agents such as polyethylene glycol 3350, used off-label per NASPGHAN guidelines, and lactulose, which carries an FDA approval for constipation broadly but without a dedicated pediatric FC indication. The priority review designation reflects the absence of approved alternatives in this younger age band. Since its 2012 launch across adult constipation indications, Linzess has been prescribed to more than 5.5 million patients in the US, according to Ironwood.


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