Ironwood, Forest Laboratories announce positive results for linaclotide Phase 3 clinical trials in IBS-C patients

Ironwood Pharmaceuticals, Inc. (NASDAQ: IRWD) and Forest Laboratories, Inc. (NYSE: FRX) 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). 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:

All secondary endpoints measured in LIN-MD 31 demonstrated statistically significant (p≤0.0014) improvements for linaclotide-treated patients compared to placebo-treated patients. These endpoints include the individual components of composite responder endpoint 2 (abdominal pain responder and CSBM responder) as well as change from baseline measures of abdominal pain, abdominal discomfort, bloating, percent pain-free days, CSBM frequency, SBM frequency, stool consistency, and straining.

• For the abdominal pain component of composite responder 2, a greater proportion of linaclotide-treated patients compared to placebo-treated patients (50.1 percent vs. 37.5 percent,>
• For the CSBM component of composite responder 2, a greater proportion of linaclotide-treated patients compared to placebo-treated-patients (48.6 percent vs. 29.6 percent, p<0.0001) had an increase of one or more CSBMs for at least six of the 12 weeks of the treatment period.

Additionally, there was no evidence of rebound worsening of abdominal pain or bowel symptoms during the randomized withdrawal period.

The most common adverse events that occurred more frequently in linaclotide-treated patients compared to placebo-treated patients were diarrhea (19 percent vs. 4 percent), flatulence (5 percent vs. 2 percent), abdominal pain (5 percent vs. 3 percent), and headache (5 percent vs. 4 percent). Overall rates of discontinuation due to adverse events were 8 percent for the linaclotide-treated patients and 3 percent for the placebo-treated patients.

Forest and Ironwood expect to present detailed results at appropriate scientific conferences.

Glossary of Terms LIN-MD-31

Spontaneous bowel movement (SBM): An SBM is a bowel movement that occurs in the absence of laxative, enema, or suppository usage during the current or preceding day.

Complete spontaneous bowel movement (CSBM): A CSBM is an SBM that is accompanied by the patient self-reporting a feeling of complete emptying of the bowel.

ROME II Criteria: A patient who reports abdominal discomfort or pain for two or more of the following three features for at least 12 weeks, which need not be consecutive, in the 12 months before the screening visit, or before starting chronic treatment with tegaserod or lubiprostone: (1) relieved with defecation; (2) onset associated with a change in frequency of stool; (3) onset associated with a change in form (appearance) of stool.

Source : Linaclotide