Nov. 2, 2009 (Business Wire) -- Ironwood Pharmaceuticals, Inc. and Forest Laboratories, Inc. (NYSE: FRX) today announced positive top-line results from two Phase 3 clinical trials assessing the safety and efficacy of once-daily dosing of the investigational drug linaclotide in patients with chronic constipation (CC). Analyses of the data indicate that in both multicenter, randomized, double-blind, placebo-controlled trials, statistical significance was achieved for the primary endpoint of 12-week complete spontaneous bowel movement (CSBM) overall responder at the two doses studied in each trial (133 mcg/day: p-values≤0.0012 and 266 mcg/day: p-values<0.0001). In both trials, statistical significance (p<0.01) was achieved for all prespecified secondary endpoints, which included measures of bloating, abdominal discomfort, and average weekly CSBMs.

“The results of these two trials confirm the potential for linaclotide to bring relief to the millions of patients suffering from many of the symptoms associated with chronic constipation,” said Howard Solomon, Chairman and Chief Executive Officer of Forest Laboratories. “These outcomes are the result of outstanding collaboration between Ironwood and Forest, with both companies participating in these clinical trials. We look forward to further advancing the development of linaclotide, a novel product in a therapeutic category where patients have very limited treatment options.”

Peter Hecht, Chief Executive Officer of Ironwood, said, “We are very pleased to observe how well the top-line results of these larger Phase 3 trials replicate the effect of linaclotide observed in our Phase 2b trial.”

These two trials are part of Ironwood and Forest’s larger Phase 3 program investigating the effect of linaclotide treatment on patients with CC or irritable bowel syndrome with constipation (IBS-C). The companies are currently enrolling two additional pivotal Phase 3 trials in North America to assess the safety and efficacy of linaclotide in patients with IBS-C and expect results in the second half of calendar year 2010.

Trial 01 Results

Trial 01 was conducted in 633 patients meeting modified Rome II criteria for CC. The trial included a two-week pretreatment baseline period and a 12-week treatment period. The primary efficacy endpoint was 12-week CSBM overall responder. A 12-week CSBM overall responder is a patient who had three or more CSBMs per week and an increase of at least one CSBM per week over baseline for at least nine of the 12 weeks of the treatment period. During the baseline period, 72 percent of patients had no CSBMs. Based on the intent-to-treat population:

• The 12-week CSBM overall responder rate was 16.0 percent in the 133 mcg linaclotide group (p=0.0012) and 21.3 percent in the 266 mcg linaclotide group (p<0.0001), a numerical increase of 2.6 and 3.5 fold, respectively, as compared to 6.0 percent in the placebo group. A total of 16.0 percent (p=0.0012) of patients receiving 133 mcg and 21.8 percent (p<0.0001) of patients receiving 266 mcg of linaclotide experienced ≥3 weekly CSBMs in at least nine out of 12 weeks as compared to 6.0 percent of patients receiving placebo. In addition 31.0 percent (p<0.0001) of patients receiving 133 mcg and 40.1 percent (p<0.0001) of patients receiving 266 mcg of linaclotide achieved an increase of ≥1 from baseline in weekly CSBMs in at least nine out of 12 weeks as compared to 13.0 percent of patients receiving placebo.
• Linaclotide-treated patients demonstrated a significant increase in average weekly CSBMs from baseline (0.6 for placebo; 2.0 for 133 mcg, p<0.0001; 2.7 for 266 mcg, p<0.0001) and a significant increase in average weekly spontaneous bowel movements (SBMs) from baseline (1.1 for placebo; 3.4 for 133 mcg, p<0.0001; 3.7 for 266 mcg, p<0.0001).