Colesevelam(Ironwood Pharmaceuticals, Inc.)

Ironwood and AbbVie said a Phase II trial assessing the drug candidate MD-7246, a delayed-release formulation of Linzess, did not meet its primary or key secondary endpoints. Following a mid-stage flop, Ironwood and AbbVie are discontinuing the development of an experimental drug aimed at the treatment of abdominal pain associated with irritable bowel syndrome with diarrhea (IBS-D). On Thursday, Ironwood and AbbVie said a Phase II trial assessing the drug candidate MD-7246, a delayed-release formulation of Linzess, did not meet its primary or key secondary endpoints. Because of that, the companies will discontinue the development of the asset. The drug was well-tolerated but, Ironwood and AbbVie said in the Phase II trial in IBS-D, patients taking MD-7246 experienced no clinically meaningful effect on bowel function. Full results from this Phase II trial are expected to be submitted for presentation at a future medical meeting. Ironwood Chief Executive Officer Mark Mallon said the companies are disappointed in the results from the Phase II study, particularly following a previous mid-stage study of the drug candidate in adult patients with IBS with constipation showed an improvement in abdominal pain. Mallon said the development of treatments for gastrointestinal uses is important but challenging. “Ironwood remains unwavering in its mission of advancing the treatment of GI diseases and redefining the standard of care for millions of GI patients,” Mallon said. Linzess, which was developed by Ironwood and Allergan, now a subsidiary of AbbVie, was first approved in 2012 as a treatment for irritable bowel syndrome with constipation and chronic idiopathic constipation. The delayed-release formulation of Linzess was designed to provide targeted delivery of linaclotide to the colon, where the majority of the abdominal pain associated with IBS is believed to originate, and to limit fluid secretion in the small intestine resulting in minimal impact on bowel function. Linzess generated approximately $803 million in sales in 2019. Mallon said Ironwood is focused on continuing to drive strong growth with Linzess, as well as completing an ongoing Phase III study of IW-3718 in refractory gastroesophageal reflux disease (GERD). IW-3718, now Ironwood’s only clinical asset, is enrolled in two Phase III studies for GERD, which impacts 8 to 10 million adults in the United States. Updates on the progress of IW-3718 are expected later this year, but with numerous clinical programs having been disrupted by COVID-19, the announcement could be pushed into 2021. Ironwood’s dearth of clinical-stage assets is due, in part, to the company’s decision last year to spin off a new company , Cyclerion Therapeutics with five compounds aimed at orphan diseases. Cyclerion launched with a mid-stage asset for sickle cell disease and a Phase II asset for heart failure and diabetic neuropathy. The company also has a Phase I program for orphan central nervous diseases.

What Brent Saunders Thinks About a Possible Allerg The drug showed a statistically significant and clinically meaningful improvement in overall abdominal symptoms compared to placebo for all primary and secondary endpoints. Ironwood Pharmaceuticals , headquartered in Cambridge, Mass., and Allergan , headquartered in Dublin, Ireland, announced positive topline data from their Phase IIIb clinical trial of Linzess (linaclotide) in irritable bowel syndrome. The drug is marketed by both companies in the U.S. for adults with irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation (CIC). In this trial, the drug was being evaluated for improvement in the overall abdominal symptoms, bloating, pain and discomfort, that adult IBS-C patients experience. The trial compared the drug to placebo. The trial also met both secondary endpoints. The drug showed a statistically significant and clinically meaningful improvement in overall abdominal symptoms compared to placebo for all primary and secondary endpoints. The primary endpoint had multiple components, but patients receiving Linzess had a 29.7% mean decrease from baseline in a weekly abdominal score of bloating, pain and discomfort through 12 weeks compared to 18.3% for patients receiving placebo. For the secondary endpoints, 40.5% receiving Linzess showed a clinically meaningful response as defined by the abdominal symptom score responder compared to 23.4% of the placebo group. The abdominal symptom score responder was defined as experiencing an improvement of at least two points from baseline in the weekly abdominal score for at least six of 12 weeks of treatment. “While research clearly suggests that the symptoms of abdominal bloating, pain and discomfort have a considerable impact on adults suffering from IBS-C, in the clinical setting patients often use the world ‘constipation’ as a general term to represent their abdominal and bowel symptoms,” stated Lin Chang, Professor of Medicine at the Vatche and Tamar Manoukian Division of Digestive Diseases at the University of California, Los Angeles (UCLA). He went on to say, “This can lead to a less precise communication regarding their symptoms between patient and physician and can impact management. I believe the data from this Linzess Phase IIIb trial will be very important in helping patients and physicians have a more comprehensive dialogue about the multiple symptoms associated with IBS-C.” Ironwood recently announced it was relocating its headquarters to a new office in downtown Boston. It is currently based in Cambridge, Mass. The new headquarters will take up about 39,000 square feet at 100 Summer Street. The company expects the move to be finished in the fourth quarter of this year and will save more than $25 million in cash payments to its landlord over the next five years. In April, Ironwood also spun off Cyclerion Therapeutics. Cyclerion is using its sGC pharmacology to discover, develop and commercialize treatments for serious and orphan diseases. Those include olinciguat for sickle cell disease, praliciquat for heart failure with preserved ejection fraction (HFpEF) and for diabetic nephropathy, and IW-6463 for orphan central nervous system diseases. Ironwood was founded in 1998 and developed Linzess for IBS-C, which launched with Allergan in 2012. Ironwood is otherwise focused on drugs for gastrointestinal disorders. IW-3718 is being evaluated for persistent GERD (gastroesophageal reflux disease) and is currently in Phase III trials. Results are expected in the second half of 2020. MD-7246 is being developed with Allergan for abdominal pain associated with IBS with diarrhea (IBS-D). The companies dosed their first patient in a Phase II trial on June 3.