Ironwood, AbbVie kick delayed-release Linzess formulation to the curb after trial failure
The delayed-release formulation of Ironwood and Allergan’s bowel drug Linzess will not see the light of day.
The experimental drug, MD-7246, failed to help patients with abdominal pain associated with irritable bowel syndrome with diarrhea (IBS-D) in a mid-stage study, prompting the partners to abandon the therapy.
First approved in 2012, Linzess (known chemically as linaclotide) enhances the activity of the intestinal enzyme guanylate cyclase-C to increase the secretion of intestinal fluid and then transit through the intestinal tract, as well as reduce visceral pain, to relieve pain and constipation associated with IBS.
MD-7246 was designed to simply deal with the pain by targeting the 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 for a minimal impact on bowel function.
Earlier this week, the partners said MD-7246 failed both the main and secondary goals of the 388 patient (IBS-D) Phase II study, but did not disclose details. Back in 2016, in a trial of 532 irritable bowel patients with constipation (IBS-C), MD-7246 did help improve abdominal pain relative to placebo with no effect on bowel function. In April, Credit Suisse’s Martin Auster had modeled ~$300 million sales opportunity for MD-7246 for Ironwood, based on the company’s sales/reimbursement apportionment with partner Allergan (now a unit of AbbVie).
With MD-7246 in the scrap heap, Ironwood is left with IW-3718 as the sole clinical-stage development program, which is currently in late-stage development for use in refractory gastroesophageal reflux disease. An update on the program was expected in the second half of this year, but will likely slide into 2021 due to Covid-19-related delays.
“As Linzess faces a 2029 horizon for generics based on existing settlements, we anticipate the company will take steps to replace the revenue from that franchise over the next several years by in-licensing new assets. We believe some value-focused shareholders may dislike this strategy,” Cowen’s Boris Peaker wrote in a note on Wednesday.
Linzess generated about $803 million in sales in 2019.
Last year, Ironwood shed its other pipeline prospects to focus on GI disorders, by spinning out a company called Cyclerion focused on the soluble guanylate cyclase (GC) — a key enzyme in the nitric oxide signaling pathway — business. The Boston drugmaker’s chief Peter Hecht left to head Cyclerion, while Ironwood brought AstraZeneca veteran Mark Mallon to the helm.