– Other Studies Highlight Impact of Linaclotide in Adult and Pediatric Populations, Highlight Disease Burden –
BOSTON--(BUSINESS WIRE)-- Ironwood Pharmaceuticals, Inc. (Nasdaq: IRWD), a GI-focused healthcare company, presented new findings during the 2022 Digestive Disease Week® (DDW) meeting that suggest colonic IW-3300 has the potential to help manage abdominopelvic visceral pain in patients with disorders of gut-brain interaction (DGBI) and related visceral pain disorders. The oral presentation, titled Colon-Targeted Delivery Of Guanylate Cyclase-C Agonist IW-3300 Relieves Comorbid Chronic Pelvic And Somatic Pain In A Rat Model Of Early Life Stress-Induced Colonic Hypersensitivity (presentation number 240), provided evidence that delivery of IW-3300 to the colorectal region inhibits overlapping chronic pelvic pain in an established preclinical model of early-life stress induced colonic hypersensitivity.
Ironwood is currently developing IW-3300, a guanylate cyclase-c (GC-C) agonist, for the potential treatment of visceral pain conditions such as interstitial cystitis/bladder pain syndrome (IC/BPS) and endometriosis. The compound is currently in Phase I trials that will lay the foundation to potentially clinically test the cross-talk hypothesis in humans for the first time. Cross-talk is a biological phenomenon where sensations of injury originating in one abdominal or visceral organ can result in altered sensation in a nearby organ because of overlapping nerve pathways.
“Visceral pain is the most common type of pain associated with disease, and yet treating patients with this type of pain remains a significant challenge,” said Beverley Greenwood-Van Meerweld, Ph.D., George Lynn Cross Research Professor Emeritus, President’s Associates Presidential Professor, University of Oklahoma Health Sciences Center. “These results are exciting because they show the potential of IW-3300 to relieve visceral pain via a neuronal cross-talk mechanism mediated by the GC-C pathway. I look forward to future results from clinical trials of the compound.”
Ironwood Pharmaceuticals and its collaborators also presented results from a post-hoc analysis of linaclotide studies focused on further understanding its treatment effect on abdominal symptoms in patients with Irritable Bowel Syndrome with Constipation (IBS-C). Other studies presented highlighted preclinical data on the impact of linaclotide on visceral hypersensitivity, data on the impact of linaclotide on pediatric functional constipation, and studies on the disease burden of IBS-C and chronic idiopathic constipation (CIC).
“As a company, we are focused on understanding the potential of linaclotide for patients who can benefit from its established mechanism treating visceral pain and constipation as well as continually expanding our pipeline to address underserved GI diseases,” said Mike Shetzline, M.D., Ph.D., chief medical officer, senior vice president and head of research and development at Ironwood. “We’re excited to present the wealth of data that we are bringing to the discussion at DDW, and particularly our efforts in pediatric patients with functional constipation as well as our IW-3300 study findings.”
Impact of Linaclotide on IBS-C
- An oral presentation titled Patient-Derived Meaningful Change Thresholds In The Novel Abdominal Score Outcome Measure In Irritable Bowel Syndrome With Constipation (presentation number 179), presented by Jan Tack, M.D., Ph.D., University of Leuven, Leuven, Belgium, summarized data from a post-hoc analysis of two Phase III randomized controlled trials of linaclotide 290 mcg versus placebo in IBS-C. Both trials evaluated meaningful changes from baseline to week 12 in Abdominal Score (AS), a composite of abdominal pain, bloating and discomfort. The post-hoc analysis, which was conducted to understand the relationship between the composite AS and patient reported global relief of abdominal symptoms found that optimal meaningful change thresholds for AS had a graded relationship to levels of perceived relief of abdominal symptoms among patients with IBS-C. An AS improvement of ~2.0 points correlated with any relief and adequate relief, while an AS improvement of ~2.5 points correlated with complete relief. The authors note that these findings may help clinicians set clinical expectations based on clinical trial results.
- A poster titled Race-Related Comparisons Of Irritable Bowel Syndrome With Constipation Symptoms, Treatment Response, And Quality Of Life: Results Of A Pooled Analysis Of Linaclotide Clinical Trials (presentation number Tu1364), presented by Linda Nguyen, M.D., Stanford Health Care, Redwood City, California, detailed findings of a post-hoc analysis of pooled studies of linaclotide in IBS-C. Overall, linaclotide demonstrated efficacy versus placebo within most racial groups based on the combined abdominal pain and constipation (APC+1) responder rate (White and Black: p