Linzess® (Linaclotide), China's First Guanylate Cyclase Agonist, Approved for IBS-C Treatment

SHANGHAI, Jan. 15, 2019 /PRNewswire/ -- AstraZeneca announced today that the National Medical Products Administration (NMPA) has officially approved Linzess, the world's first-in-class guanylate cyclase agonist.^®(Linaclotide) launched in China. As a prescription drug specifically indicated for the treatment of adult irritable bowel syndrome with constipation (IBS-C) in China, Linzess^®Its approval will fill the treatment gap for adult constipation-predominant irritable bowel syndrome (IBS-C) in China, bringing hope to a vast number of domestic patients.

Linaclotide has been approved for marketing in more than 30 countries worldwide, including the United States. Currently, linaclotide has become the leading prescription drug globally for the treatment of irritable bowel syndrome with constipation (IBS-C). AstraZeneca and Ironwood Pharmaceuticals entered into a collaboration in 2012 to jointly be responsible for Linzess.^®Development and Launch Promotion in China.

Constipation-predominant Irritable Bowel Syndrome (IBS-C) is a functional bowel disorder characterized by recurrent episodes of constipation accompanied by abdominal pain, bloating, and abdominal discomfort, which significantly impairs work and quality of life. It has a high prevalence in China, with at least 14 million patients affected.^[1]Plagued by distress.

Linzess^®Its innovative mechanism involves activating the body’s endogenous guanylate cyclase, thereby promoting intestinal fluid secretion and reducing visceral hypersensitivity, which simultaneously alleviates symptoms such as abdominal pain, bloating, and constipation in patients with constipation-predominant irritable bowel syndrome (IBS-C). Compared with placebo, more than 60% of patients achieved spontaneous bowel movements within one day of treatment.^[2] ; Within one week, the patient's severe abdominal pain and frequency of complete spontaneous bowel movements both showed significant improvement.^[6]; Nearly 90% of patients experienced a significant increase in the frequency of spontaneous bowel movements throughout the treatment cycle, and nearly 80% of patients showed significant improvement in abdominal pain and bloating.^[2]。

Professor Chen Minhu, Chairman of the Chinese Society of Gastroenterology under the Chinese Medical Association and Vice President of the First Affiliated Hospital of Sun Yat-sen University, stated, “Constipation-predominant irritable bowel syndrome (IBS-C) is a condition that adversely affects quality of life, and current treatment options are very limited. The approval of linaclotide for market availability provides a new therapeutic option for patients with irritable bowel syndrome and will promote the standardization and normalization of IBS-C management, holding significant importance for improving the diagnosis and treatment of IBS-C in China.”

Professor Tang Chengwei, Incoming Chairman of the Chinese Society of Gastroenterology and Director of the Department of Gastroenterology at West China Hospital of Sichuan University, stated: “Linaclotide is the first guanylate cyclase agonist approved in mainland China. The launch of this innovative medication will provide better treatment options for patients in China with constipation-predominant irritable bowel syndrome (IBS-C), helping them alleviate symptoms from a new perspective and improve their quality of life.”

Mr. Chen Zhijian, Senior Vice President of Global Drug Development at AstraZeneca and President of China New Drug Development, stated: “AstraZeneca’s China New Drug Development department has always been ‘patient-centric,’ committed to identifying and addressing the most urgent treatment needs of patients in China. Linzeshu^®Its approval will bring a groundbreaking therapeutic option to patients in China with constipation-predominant irritable bowel syndrome (IBS-C), enabling them to enjoy a life free from bloating and pain, and thus ‘easier’ bowel movements.

"As an innovative prescription medication for the treatment of constipation-predominant irritable bowel syndrome, Linzess"^®“Filling a treatment gap in China.” Mr. Wang Lei, Global Executive Vice President of AstraZeneca and President of International Business and China, stated, “In the future, AstraZeneca will continue to make it its mission to introduce the world’s most innovative medicines to China, while collaborating closely with professional societies, physicians, and partners in the field of gastroenterology to improve drug accessibility, ensuring that patients in China can benefit from international novel therapies at the earliest opportunity.”

Regarding Constipation-predominant Irritable Bowel Syndrome (IBS-C) and Its Current Treatment Status in China

Irritable Bowel Syndrome (IBS) is a common functional bowel disorder in clinical practice. Constipation-predominant irritable bowel syndrome (IBS-C) is one of its subtypes, characterized clinically by recurrent constipation accompanied by abdominal pain, bloating, and abdominal discomfort related to defecation. Due to its recurrent nature, IBS-C adversely affects patients' quality of life. In China, the prevalence of IBS is as high as 6.5%, with 15% of cases being IBS-C.^[4] . Currently, there are no targeted and effective therapeutic drugs for IBS-C in China.^[3] , treatment primarily involves selecting appropriate medications based on symptoms, such as antispasmodics and osmotic laxatives.

About Linaclotide

Linaclotide, a guanylate cyclase-C agonist, is an innovative drug recommended by the American Gastroenterological Association (AGA) guidelines for the treatment of irritable bowel syndrome with constipation (IBS-C), and it is also a standard therapy for IBS-C (recommendation grade: strong; level of evidence: high).^[5]. A Phase III clinical trial in China confirmed that, compared with the placebo group, linaclotide significantly alleviated IBS-C–related symptoms, with the proportion of responders achieving symptom relief more than double that of the placebo group (31.7% vs. 15.4%). The therapeutic effect was evident as early as the first week of treatment, and symptoms continued to improve throughout the treatment period.^[3]。Furthermore, since linaclotide acts locally in the intestine and is minimally absorbed into the bloodstream, it has a more favorable safety profile. Studies have shown that the most common adverse reactions to linaclotide are mild to moderate diarrhea, with no clinically significant sequelae observed.^[3]。

Linzeshu^®YesIronwoodRegistered trademark of [Name] Pharmaceutical Co., Ltd.

[1] Zhang L, Duan LP, Liu YX, et al. Prevalence and associated risk factors of irritable bowel syndrome in the Chinese population: a meta-analysis [J]. Chinese Journal of Internal Medicine. 2014;53(12):969-975. DOI: 10.3760/cma.j.issn.0578-1426.2014.12.011.

[2] Chey WD, Lembo AJ, et al. Am J Gastroenterol. 2012 Nov;107(11):1702-12.

[3] Yang Y, Fang J, et al. J Gastroenterol Hepatol. 2018 33(5)

[4] Gastrointestinal Functional Disorders Collaboration Group, Society of Digestive Diseases, Chinese Medical Association. Expert consensus on irritable bowel syndrome in China (2015, Shanghai) [J]. Chinese Journal of Digestion, 2016, 36(5): 299-312.

[5] Weinberg DS, et al. Gastroenterology 2014;147(5):1146–1148.

[6] Rao S, et al. Gastroenterol 2012; 107:1714–1724;