The FDA (Food and Drug Administration) recently approved the once-daily oral capsule, Linzess, for adults of either sex who suffer from IBS-C (IBS with constipation) or CIC (chronic idiopathic constipation).
Linaclotide is the only FDA-approved GC-C (guanylate cyclase-C) agonist that acts locally in the gut. Ironwood Pharmaceuticals says this is the first new prescription option for adults with these disorders in over six years.
About Linzess (linaclotide)Linzess (linaclotide) is the "first and only guanylate cyclase‐C (GC‐C) agonist approved by the FDA for the treatment of both irritable bowel syndrome with constipation (IBS‐C) and chronic idiopathic constipation (CIC) in adults", according to Ironwood Pharmaceuticals.
Linzess is taken orally, in capsule form, once a day. It helps relieve the pain and constipation linked to IBS-C and constipation and hard stools experienced by patients with CIC.
The recommended doses are:
- 290 mcg for IBS‐C patients
- 145 mcg for CIC patients
Scientists believe Linzess works in two ways "Linzess binds to the GC‐C receptor locally, within the intestinal epithelium. Activation of GC‐C results in increased intestinal fluid secretion and transit and a reduction in visceral pain, which is thought to be mediated by decreased activity of pain‐sensing nerves. The clinical relevance of the effect on pain fibers in nonclinical studies has not been established."
In randomized, placebo-controlled Phase III human studies involving over 2,800 adults, Linzess was shown to alleviate abdominal pain in patients with IBS-C, as well as increasing bowel movement frequency among those with CIC and IBS-C.
Abdominal pain relief was reported during the first week of treatment and was maintained during the whole of the 12-week treatment period. Maximum effect on constipation was seen during week two, and on abdominal pain at weeks 6 to 9.
A subset of patients who had been on Linzess were switched over to placebo during the trial. They reported that their symptoms went back to pretreatment levels within seven days. Some placebo patients were switched over to Linzess and reported improvements soon after taking the medication.
Linzess should not be taken by patients up to the age of six years. The medication should be avoided in patients aged from 6 to 17 years. Animal studies showed that a clinically relevant adult dose of linaclotide caused deaths in juvenile mice. No trials have been carried out on children. The most commonly reported side effect associated with Linzess treatment was diarrhea.
Linzess is being co-promoted by Ironwood and Forest in the USA. Linaclotide, which was also approved in the European Union, will be marketed under the brand name Constella through a licence agreement between Ironwood and Almirall S.A. The development and commercialization in Japan and other Asian markets will be done via agreements between Ironwood and Astellas Pharma Inc. and AstraZeneca.
Irritable Bowel Syndrome with ConstipationUp to 13 million people are thought to have irritable bowel syndrome with constipation (IBS‐C) in the USA. It is a chronic functional gastrointestinal disorder. IBS‐C symptoms can be severe enough to seriously undermine a patient's ability to properly carry out daily living duties.
Patients typically suffer recurring abdominal discomfort or pain, constipation, hard or lumpy stools in over 25% of their bowel movements, and soft/watery stools in less than 25%.
Ironwood says there are very few approved therapies for IBS‐C available today.
Chronic Idiopathic ConstipationCIC (chronic idiopathic constipation) is thought to affect up to 35 million Americans today. It is a functional gastrointestinal disorder in which the sufferer has fewer than three bowel movements each week for at least three months.
CIC patients may also have a sensation of incomplete evacuation after going to the toilet, as well as hard stools.
Written by Christian Nordqvist