Ironwood’s Linaclotide Set For China Filing On New Results
This article was originally published in PharmAsia News
Executive Summary
Ironwood's irritable bowel syndrome drug linaclotide has come out well from a Phase III trial conducted predominantly in China, setting the stage for a filing in this potentially large market where no prescription drug are currently available for its intended indication.
Ironwood Pharmaceuticals Inc. and partner AstraZeneca PLC have released positive top-line results from a trial conducted mainly at sites in China in adults with irritable bowel syndrome with constipation (IBS-C).
The statistically significant improvements over placebo against the co-primary endpoints and in all pre-specified secondary endpoints, such as abdominal pain and discomfort, mean that the trial will be among the data used to support a planned regulatory filing to the China FDA in the early part of 2016.
A subsequent approval would make the guanylate cyclase type C receptor agonist the first prescription therapy for both male and female patients suffering from IBS-C. The disorder, characterized by abdominal pain, bloating and reduced bowel movements, affects an estimated 13 million people in China, the firms noted.
The 839-patient study was conducted mainly in China but also included sites in Australia, New Zealand, Canada and the U.S. For the two primary endpoints, 60.0% of those receiving linaclotide 290mcg daily were 12-week Abdominal Pain/Discomfort Responders (defined as a patient who has at least a 30% improvement in abdominal pain or discomfort for at least half of the 12-week period), versus 48.8% of those on patients (p=0.001).
31.7% of those on linaclotide were IBS Degree of Relief Responders (who rate their symptoms as being "considerably relieved" or "completely relieved" for at least half of the 12-week period), compared with 15.4% of those on placebo (p<0.0001).
Both these primary endpoints were similar to those used to support the successful EU approval of the drug, but the results were also significant according to the U.S. FDA's IBS endpoint, at 33.7% for linaclotide and 17.4% for placebo (nominal p<0.0001). The FDA looks at patients reporting at least a 30% reduction from baseline in abdominal pain and an increase of at least one complete spontaneous bowel movement from baseline, all in the same week, for at least six out of 12 weeks.
The most common adverse event in linaclotide patients in the newly reported trial was diarrhea (9.4% versus 1.2% for placebo).
Full results from the study will be presented at an unspecified medical congress.
Commercial Terms
Linaclotide is being jointly developed and commercialized in China with AstraZeneca under a deal worth $25 million upfront to Cambridge, Massachusetts-based Ironwood. The two firms will share any net profits or losses in China, 55% in favor of AstraZeneca initially, moving to a 50/50 split once a pre-specified milestone is met. [See Deal]
If certain sales targets are reached, Ironwood is also eligible for $125 million in additional commercial milestones.
In a new report, China’s National Health and Family Planning Commission has drawn attention to the increasing numbers of people suffering from chronic health disorders in the country (of which IBS is one), and is looking at measures to improve prevention and treatment (Also see "China Looks At Innovation, Quality Policies As Chronic Diseases Rise" - Scrip, 9 Jul, 2015.).
The new results mean linaclotide has now met all primary and secondary endpoints in the six Phase III trials it has completed, and any approval in China would add to those for IBS-C in a number of markets. These include the U.S., where it is sold as Linzess (co-marketed by Ironwood and Actavis Group ) and also indicated for chronic idiopathic constipation, and Europe, where Almirall SA markets it as Constella for IBS-C
Linaclotide is also partnered with Astellas Pharma Inc. in Japan, where Phase III trials are underway for IBS-C and a Phase II program for chronic constipation.
The drug acts by activating guanylate cyclase receptors in the intestinal epithelium, which increases fluid secretion and accelerates bowel transit while also decreasing pain nerve activity.
Additional indications under investigation by Ironwood include opioid-induced constipation, pediatric use and colon cancer prevention, and a colonic release formulation is also in development.