Linaclotide

Linaclotide is a drug being studied to relieve symptoms of abdominal pain, discomfort, bloating, and bowel symptoms in people who have irritable bowel syndrome with constipation (IBS-C), or chronic constipation. It has proved safe and effective in trials, but is not yet FDA or EMA approved. In studies, patients taking Linaclotide experienced improvement in multiple symptoms including pain or discomfort, bloating, and bowel function. 

Ironwood and Forest Report the U.S. FDA has Accepted for Review the New Drug Application for Linaclotide for the Treatment of Irritable Bowel Syndrome with Constipation and Chronic Constipation

October 24, 2011 The FDA has accepted for review the New Drug Application (NDA) for linaclotide to treat irritable bowel syndrome with constipation (IBS-C) and chronic constipation (CC). The review, which will determine whether or not the FDA approves the drug, is expected to take 10 months with a target date to occur in June 2012.

Ironwood Announces Submission of Marketing Authorization Application for Linaclotide for the Treatment of IBS-C in Europe

September 29, 2011 – Ironwood Pharmaceuticals, Inc. today announced that its European partner Almirall, S.A. submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for linaclotide, a guanylate cyclase type-C (GC-C) agonist, for the treatment of irritable bowel syndrome with constipation (IBS-C).  Once approved, linaclotide will be marketed in Europe under the trademark Constella®.

 

Ironwood and Forest Announce Submission of New Drug Application in the U.S. for Linaclotide for the Treatment of Irritable Bowel Syndrome with Constipation and Chronic Constipation

August 9, 2011 – Ironwood Pharmaceuticals, Inc. and Forest Laboratories, Inc. today announced they have recently submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for linaclotide, a guanylate cyclase type-C (GC-C) agonist, for the treatment of irritable bowel syndrome with constipation (IBS-C) and chronic constipation (CC).

The submission includes efficacy and safety data from a Phase 3 program comprising four double-blind placebo-controlled trials and two open-label long term safety studies. A total of more than 2,800 patients received a once-daily dose of either linaclotide or placebo across the four placebo-controlled clinical trials: two trials in patients with IBS-C and two trials in patients with CC. In these trials, statistically significant improvements in abdominal and bowel symptoms were achieved for linaclotide-treated patients versus placebo-treated patients for all primary and secondary endpoints.

Safety data collected across the four placebo-controlled Phase 3 clinical trials demonstrated that diarrhea was the most commonly reported adverse event and led to study discontinuation in 4 percent to 5 percent of linaclotide-treated patients compared to fewer than 1 percent of patients receiving placebo. Additionally, over 3,200 patients have enrolled in ongoing open-label safety studies and more than 1,100 of those patients have received linaclotide for at least 12 months.

Results Positive from Second of Two Phase 3 Trials of Linaclotide for Treatment of Patients with IBS-C

November 1, 2010 – Ironwood Pharmaceuticals, Inc. and Forest Laboratories, Inc. today announced positive top-line results from the second of two Phase 3 clinical trials assessing the efficacy and safety of the investigational drug, linaclotide, in patients with irritable bowel syndrome with constipation (IBS-C). The trial was a multicenter, randomized, double-blind, and placebo-controlled conducted in 805 IBS-C patients.  The trial included a 26-week treatment period with patients receiving a once-daily dose of linaclotide or placebo.

Statistically significant improvement was achieved for patients treated with linaclotide compared to placebos for measures of abdominal pain, abdominal discomfort, bloating, and bowel symptoms.  The safety results were consistent with those observed in previous linaclotide trials; no serious side effects related to treatment were reported. Diarrhea is the most common adverse event in linaclotide-treated patients.  

Ironwood and Forest have now reported positive results from two Phase 3 trials in patients with IBS-C and two Phase 3 trials in patients with chronic constipation (CC). The IBS-C trials were also designed to support regulatory submission in Europe, where linaclotide is out-licensed to Almirall; positive top-line results from this study are reported for the E.U. endpoints.

Results Positive from First of Two Phase 3 Trials of Linaclotide for Treatment of Patients with IBS-C

September 13, 2010 – Ironwood Pharmaceuticals, Inc. and Forest Laboratories, Inc. today announced positive top-line results from the first of two Phase 3 clinical trials assessing the efficacy and safety of the investigational drug, linaclotide, in patients with irritable bowel syndrome with constipation (IBS-C). The trial was a multicenter, randomized, double-blind, and placebo-controlled conducted in 803 patients.  

Statistically significant improvement was achieved for patients treated with linaclotide compared to placebos for measures of abdominal pain, abdominal discomfort, bloating, and bowel symptoms.  The safety results were consistent with those observed in previous linaclotide trials; no serious side effects related to treatment were reported. Diarrhea is the most common adverse event in linaclotide-treated patients.  The second Phase 3 trial of linaclotide in IBS-C is ongoing. Results are expected later this year.

Ironwood and Forest are co-developing linaclotide in the United States. Ironwood has out-licensed linaclotide to Almirall for development in Europe; and to Astellas Pharma Inc. for development in Japan, Indonesia, Korea, the Philippines, Taiwan, and Thailand.

Linaclotide Shows Promise as a Treatment for Patients with IBS with Constipation (IBS-C)

November 2009 – Linaclotide™ is a promising, first-in-class drug for the treatment of irritable bowel syndrome with constipation (IBS-C) and chronic constipation. It is now in Phase 3 clinical development.

At therapeutic doses, linaclotide acts locally in the gut. Exposure in the body outside the gut has not been detected. The drug is taken orally once daily.

In previous, Phase 2, trials patients taking linaclotide experienced statistically significant improvement in multiple symptoms. Over a 12-week treatment period, patients with IBS-C reported reduced abdominal pain, discomfort, and bloating, as well as improved bowel function. Over a 4-week treatment period, patients with chronic constipation reported reduced constipation, abdominal discomfort, and bloating.

No serious side effects related to treatment were reported in the trials. Diarrhea was the most commonly reported side effect in both groups.

About Phase 3 Trials

Phase 3 clinical trials involve studies of people to confirm a drug’s safety and effectiveness. Appropriate regulatory agencies review trial results for approval before the drug can be prescribed.

About the New Drug Application Process

The New Drug Application (NDA) is the vehicle through which drug sponsors formally propose that the U.S. Food and Drug Administration (FDA) approve a new pharmaceutical for sale and marketing in the U.S.

The goals of the NDA are to provide enough information to permit FDA reviewer to reach the following key decisions:

 

• Whether the drug is safe and effective in its proposed use(s), and whether the benefits of the drug outweigh the risks.

 

• Whether the drug's proposed labeling (package insert) is appropriate, and what it should contain.

 

• Whether the methods used in manufacturing the drug and the controls used to maintain the drug's quality are adequate to preserve the drug's identity, strength, quality, and purity.