Dr Reddys Gets CDSCO Panel Nod To Manufacture, Market Linaclotide Capsules for Chronic Idiopathic Constipation

New Delhi: Pharmaceutical major Dr Reddy's has got approval from the Subject Expert Committee (SEC) functional under the Central Drug Standard Control Organisation (CDSCO) to manufacture and market Linaclotide Capsules 72 mcg and 145 mcg for Chronic Idiopathic Constipation (CIC) in adults only.

However, the expert panel also mentioned that the committee did not recommend two capsules of 145 mcg to be used for Irritable Bowel Syndrome with Constipation (IBS-C) in adults. The committee further recommended that the firm is required to develop 290 mcg Linaclotide capsules for IBS-C in adults.

This came after Dr. Reddy's Laboratories presented Phase III clinical trial results for the protocol titled “A randomized, Multicentre, double blind, placebo-controlled, parallel group study to evaluate the efficacy and safety of Linaclotide once daily of the test product in patients with chronic constipation.” before the committee.

Linaclotide is a guanylate cyclase-C agonist used to treat different types of constipation, such as irritable bowel syndrome-related constipation, idiopathic constipation, and functional constipation.

Linaclotide is a potent, highly selective agonist of guanylate cyclase-C (GC-C), a soluble and single-membrane-spanning enzyme on the luminal surface of intestinal epithelial cells. GC-C regulates chloride secretion.

Linaclotide has a dual mode of action. Firstly, linaclotide and its active metabolite bind to transmembrane GC-C. Activation of GC-C results in an increase in both intracellular and extracellular concentrations of cyclic guanosine monophosphate (cGMP). Elevated intracellular cGMP activates the cGMP-dependent protein kinase II (PKG-II), which phosphorylates and activates the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel expressed on the apical surface of intestinal epithelial cells. CFTR activation promotes the secretion of chloride and bicarbonate ions and inhibits sodium absorption, resulting in increased intestinal fluid and accelerated GI transit.

Secondly, linaclotide exerts anti-nociceptive effects by reducing visceral hypersensitivity. Increased levels of extracellular cGMP in the submucosa inhibit colonic nociceptors, relieving intestinal pain.

At the recent SEC meeting for gastroenterology and hepatology held on January 21, 2025, the expert panel reviewed the Phase III clinical trial results for the protocol titled “A randomized, multicentre, double blind, placebo-controlled, parallel group study to evaluate the efficacy and safety of Linaclotide once daily of the test product in patients with chronic constipation.”

After detailed deliberation, the committee recommended the grant of permission to manufacture and market the drug Linaclotide Capsules (72 mcg and 145 mcg) for the indication of Chronic Idiopathic Constipation (CIC) in adults only.

The committee did not recommend two capsules of 145 mcg to be used for Irritable Bowel Syndrome with Constipation (IBS-C) in adults. The committee recommended that the firm is required to develop 290 mcg Linaclotide capsules for IBS-C in adults.

In view of the above, the expert panel further suggested that the firm is required to submit the revised package insert with respect to the following points:

1) CIC: 145 mcg orally once daily or 72 mcg orally once daily based on individual presentation or tolerability.

2) The firm should delete the IBS-C indication from the package insert.

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