Following Phase II Failure, Ironwood and AbbVie Halt Development of Delayed-Release Linzess


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.

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