Ironwood Pharmaceuticals, Inc. announced that a new drug application (NDA) seeking approval of linaclotide for the treatment of adults with irritable bowel syndrome with constipation (IBS-C) in Japan was filed with the Japanese Ministry of Health, Labor and Welfare by Astellas Pharma Inc., Ironwood’s partner for linaclotide in Japan.
Linaclotide is a guanylate cyclase-C (GC-C) receptor agonist currently approved, and is the branded prescription market leader, for the treatment of adults with IBS-C or chronic idiopathic constipation (CIC) in the United States, where more than 40 million patients are estimated to suffer from these conditions. To date, more than 1 million unique US patients have filled a linaclotide prescription since its launch in December 2012, according to IMS Health. Linaclotide is also approved for adults with IBS-C or CIC in more than 30 other countries.
“Today’s filing for regulatory approval in Japan by our partner Astellas, and our recent filing for regulatory approval in China with our partner AstraZeneca, are important achievements by Ironwood and our global partners toward bringing linaclotide to appropriate patients around the world,” said Mark Currie, Ph.D., chief scientific officer and president of research and development at Ironwood. “In Japan, 2.9 percent of adults are estimated to suffer from IBS-C, with no prescription medicines currently approved for this disease. We hope to help address this unmet need, and we continue to explore further innovation with linaclotide across a broad spectrum of patient needs.”
The NDA submission in Japan is based mainly on the results obtained from the double-blind, placebo-controlled, parallel-group comparative phase III study conducted in Japan in adults with IBS-C, which demonstrated linaclotide’s clinical efficacy and safety profile, and which were announced by the companies in November 2015.
Ironwood and Astellas entered into a licensing agreement in 2009 to develop and commercialise linaclotide in Japan for the treatment of IBS-C, chronic constipation and other gastrointestinal conditions. Per the agreement, Astellas paid Ironwood a $30 million upfront licensing fee and a $15 million development milestone payment upon enrollment of the first patient in the phase III IBS-C trial. These payments are in addition to the $15 million milestone payment earned by Ironwood upon the NDA submission announced recently. The agreement also includes an additional $15 million milestone payment for Ironwood upon receipt of approval of linaclotide by the Japan regulatory authority. The agreement also provides for Ironwood to receive royalties, which escalate based on sales volume, if linaclotide is approved in Japan.
Linaclotide is a guanylate cyclase-C (GC-C) agonist that is thought to work in two ways based on nonclinical studies. Linaclotide binds to the GC-C receptor locally, within the intestinal epithelium. Activation of GC-C results in increased intestinal fluid secretion and accelerated transit and a decrease in the activity of pain-sensing nerves in the intestine. The clinical relevance of the effect on pain fibers, which is based on nonclinical studies, has not been established. Linaclotide is marketed by Ironwood and Allergan plc in the United States as Linzess and is indicated for the treatment of adults with irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation (CIC), with more than 1 million unique patients in the United States having filled more than 4 million linaclotide prescriptions since launch, according to IMS Health. Linaclotide is marketed by Allergan for the treatment of adults with moderate to severe IBS-C in Europe under the brand name Constella. Ironwood also has partnered with Astellas for development and commercialisation of linaclotide in Japan and with AstraZeneca for development and commercialisation in China, Hong Kong and Macau.