Ironwood And Forest Announce Positive Linaclotide Results From Phase 3 Trial In Patients With Irritable Bowel Syndrome With Constipation

Ironwood Pharmaceuticals, Inc. (NASDAQ: IRWD) and Forest Laboratories, Inc. (NYSE: FRX) today announced positive top-line results from the firs 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). Analyses of the data indicate clinically meaningful and statistically significant improvement was achieved for linaclotide-treated patients compared to placebo-treated patients for all four primary efficacy endpoints, which included two composite responder endpoints encompassing abdominal pain and complete spontaneous bowel movements (CSBMs), as well as individual responder endpoints for abdominal pain and CSBMs. Significant improvement was also achieved for linaclotide-treated patients compared to placebo-treated patients for all pre-specified secondary endpoints, which are measures of abdominal pain, abdominal discomfort, bloating, and bowel symptoms. The safety results were consistent with those observed in previous linaclotide trials, with diarrhea being the most common adverse event in linaclotide-treated patients. A second Phase 3 trial of linaclotide in IBS-C is ongoing with top-line results expected in Q4 2010.


"There are millions of patients suffering from IBS-C and limited treatment options to address both their abdominal pain and bowel symptoms, which were improved in this first clinical study"


"The results of this Phase 3 trial, combined with the previously reported positive IBS-C and chronic constipation trial results, further support our belief that linaclotide has the potential to improve abdominal pain and bowel symptoms, offering a promising treatment for more than 30 million individuals suffering from these chronic gastrointestinal disorders," said Peter Hecht, Chief Executive Officer of Ironwood.


"There are millions of patients suffering from IBS-C and limited treatment options to address both their abdominal pain and bowel symptoms, which were improved in this first clinical study," said Howard Solomon, Chairman and Chief Executive Officer of Forest Laboratories. "These results are very promising. We believe linaclotide will be a valuable treatment for these patients. We look forward to receiving the results of the second pivotal trial in Q4 2010."


This trial, LIN-MD-31, is part of Ironwood and Forest's Phase 3 program investigating the effect of linaclotide treatment on patients with IBS-C or chronic constipation (CC). Previously, Ironwood and Forest reported positive results of two Phase 3 trials in patients with CC. The companies expect to file a New Drug Application in mid-2011 in the United States. The IBS-C trials were designed to also support regulatory submission in Europe. Today, in a separate press release, Ironwood and its European partner, Almirall, announced top line results from LIN-MD-31 for the E.U. endpoints.
Trial LIN-MD-31 Primary Efficacy Endpoint Results















Trial LIN-MD-31 was a multicenter, randomized, double-blind, placebo-controlled trial conducted in 803 patients meeting modified Rome II criteria for IBS-C. The trial included a two-week pretreatment baseline period, a 12-week treatment period with patients receiving either a 266 mcg once daily dose of linaclotide or placebo, and a four-week randomized withdrawal period. During the pretreatment baseline period, the mean abdominal pain score was 5.6 (on a 0 - 10 scale where 0 is no abdominal pain and 10 is very severe abdominal pain), with 88 percent of patients suffering from abdominal pain every day, 76 percent of patients had no CSBMs. The results for the four primary endpoints are detailed below:


1. Composite responder endpoint 1: abdominal pain and CSBM


- A greater proportion of linaclotide-treated patients compared to placebo-treated patients (12.1 percent vs. 5.1 percent, p=0.0004) had, in the same week, at least a 30 percent reduction in abdominal pain, at least three CSBMs, and an increase of one or more CSBMs. These criteria had to be met for at least nine of the 12 weeks of the treatment period for a patient to be considered a responder for composite responder endpoint 1.



2. CSBM responder endpoint:


- A greater proportion of linaclotide-treated patients compared to placebo-treated patients (19.5 percent vs. 6.3 percent, pBuy Allegra Online no Prescription