Linzess (linaclotide), for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation, has been approved by the Food and Drug Administration (FDA), USA. The approval is for adult patients only. “Idiopathic” means “of unknown cause”.

Chronic constipation affects approximately 63 million Americans, says the NIH (National Institutes of Health). If a patient continues suffering from persistent constipation after receiving standard treatment for the condition, doctors generally diagnose it as “chronic idiopathic constipation”.

The active ingredient of Linzess is linaclotide, a first-class GC-C (guanylate cyclase) agonist that acts locally in the gut with negligible systemic exposure.

Health authorities in the USA estimate that over 15 million people in the country are affected by irritable bowel syndrome (IBS). A subtype of IBS, called IBS-C (irritable bower syndrome with constipation) is characterized by hard and/or lumpy stools and abdominal pain.

Linzess (linaclotide) is an oral medication; the capsule should be taken on an empty stomach at least 30 minutes before the first meal of the day. Linzess makes the bowels move more frequently. Studies have shown that Linzess may also relieve the symptoms of abdominal pain.

Victoria Kusiak, M.D., deputy director of the Office of Drug Evaluation III in FDA’s Center for Drug Evaluation and Research, said:

“No one medication works for all patients suffering from these gastrointestinal disorders. With the availability of new therapies, patients and their doctors can select the most appropriate treatment for their condition.”

FDA investigators assessed the safety and efficacy of Linzess for the treatment of irritable bowel syndrome with constipation in two double-blind human studies involving 1,604 patients. The patients were randomly selected to receive either a placebo (dummy drug) or 290 micrograms of Linzess – the treatment period lasted 12 weeks.

Both studies demonstrated Linzess’ clear superiority over placebo in relieving abdominal pain and facilitating more frequent complete spontaneous bowel movements.

Another two double-blind clinical trials involving 1,272 patients were also assessed for efficacy and safety by the FDA. The patients were randomly selected to receive Linzess at doses of 145 mcg or 290 mcg, they were compared to patients in a placebo group. This trial also had a treatment-period of 12 weeks. Linzess was shown to be significantly superior to placebo in facilitating more frequent complete bowel movements, as well as reducing abdominal pain symptoms. The 145 mcg dose was approved, but not 290 mcg, because it was found to be no better than the lower dosage.

William D. Chey, M.D., professor of gastroenterology at the University of Michigan Health System, who was involved in the clinical trials, said:

“The symptoms experienced by patients with IBS-C and chronic idiopathic constipation can have a significant impact on affected individuals. The approval of Linzess provides physicians with a new, evidence-based, effective treatment option for their adult patients with IBS-C and chronic idiopathic constipation.”

A Boxed Warning warns that Linzess cannot be used with patients aged under 18 years. Trial results showed that the most common side effect was diarrhea.

Linzess was developed jointly by two pharmaceutical companies – Ironwood Pharmaceuticals Inc. (Cambridge, Mass.) and Forest Pharmaceuticals Inc. (St. Louis, Mo.). According to an FDA communiqué today, the drug will also be co-marketed by both companies.

Howard Solomon, Chairman, Chief Executive Officer and President of Forest Laboratories, said:

“The approval of Linzess validates Forest and Ironwood’s commitment to bringing forth an effective treatment in disease categories that previously had limited treatment options. We look forward to making this treatment available to the millions of adults with IBS-C and CIC in the United States. This achievement is the result of our close working relationship with Ironwood over the past five years in the development of this exciting product.”

Irritable bowel syndrome with constipation, or IBS-C is a chronic functional gastrointestinal disorder. IBS-C can sometimes undermine a patient’s ability to carry out daily living activities. Typically, symptoms include abdominal pain/discomfort, at least one-quarter of all bowel movements have hard or lumpy stools, and less than one-quarter of all bowel movements have soft or water stools.

There are very few therapies available to effectively treat IBS-C.

Chronic idiopathic constipation (CIC), also known as functional constipation, is one that does not appear to have a physiological or physical cause. Experts suspect the cause is probably psychological, neurological or psychosomatic.

People with chronic idiopathic constipation are generally healthy, but have problems with their bowel movements.

Patients with CIC defecate (empty their bowels) fewer than three times per week for a period of at least three months. Many, even when they empty their bowels, feel that the evacuation was incomplete. According to Ironwood Pharmaceuticals, up to 35 million people in the USA probably suffer from CIC-type signs and symptoms.

Written by Christian Nordqvist