AstraZeneca submits the listing application of linaclonide, a new constipation drug, to CFDA

Ironwood and its partner, Asteris, recently announced that they have submitted an application to the Ministry of health, labor and welfare of Japan (MHLW) for the listing of linaclonide, a new constipation drug, to seek approval for the treatment of adult patients with constipation type irritable bowel syndrome (IBS-C) Linaclonide is a guanosine cyclase-C (GC-C) agonist, which can bind and locally act on GC-C receptors on the surface of intestinal epithelial lumen The activation of GC-C results in the increase of cGMP concentration both in and out of cells The increase of cGMP in cells stimulated the secretion of chloride and bicarbonate ions into intestinal cavity, resulting in the increase and acceleration of intestinal secretion In the animal model, linaclonide also showed the effect of reducing intestinal pain, which is believed to be mediated by the increase of extracellular cGMP, reducing the activity of pain sensing nerves in the intestinal tract, thus inducing the reduction of visceral pain At present, linaclonide is the market leader of brand medicine prescription in the field of constipation treatment In the United States, linaclonide has been approved by FDA in 2012 for the treatment of adult patients with constipation type irritable bowel syndrome (IBS-C) and chronic idiopathic constipation (CIC) In addition, linaclonide has been approved for use in IBS-C or CIC adult patients in more than 30 countries around the world It is estimated that 2.9% of adults in Japan suffer from IBS-C, and there is no prescription drug approved to treat the disease The submission of linaclonide NDA in Japan is based on the positive data of a double-blind, placebo-controlled, parallel group comparison phase III study conducted in IBS-C adult patients in Japan, which confirmed that linaclonide has significant clinical efficacy and safety The data was published in November 2015 Linaclonide was discovered by Ironwood In 2009, Ansteel signed a license agreement with Ironwood to develop and commercialize linaclonide in Japan for the treatment of IBS-C, chronic constipation and other gastrointestinal diseases In the United States, linaclotide is called linzess, which is jointly marketed by Ironwood and Allergan In Europe, linaclonide is called Constella and is marketed by Elgin AstraZeneca: linaclonide will become the first prescription drug for IBS-C patients in China In addition, AstraZeneca and Ironwood reached a cooperation in 2012 to jointly take charge of the development and commercialization of linaclonide in China (including Hong Kong and Macao) According to the terms of the agreement, AstraZeneca paid an advance payment of US $25 million, and both parties will share the net profit and loss In addition, Ironwood will be eligible for an additional $125 million commercialization milestone payment The two sides hope to take this opportunity to enter the huge and fast-growing Chinese market of linaclide, so as to obtain more profits Recently, AstraZeneca submitted its listing application to China food and Drug Administration (CFDA) If approved, linaclonide will be the first prescription drug specifically for IBS-C patients in the Chinese market It is estimated that there are about 13 million IBS-C patients in China This submission is based on positive top line data from a phase III study conducted in China This study was carried out in adult patients with constipation type irritable bowel syndrome (IBS-C) in China The data showed that linzess reached all primary and secondary endpoints Compared with placebo, linaclonide can significantly reduce abdominal pain and improve constipation symptoms.