AstraZeneca Secures Exclusive Rights to Develop, Manufacture, and Commercialize Linzess® (Linaclotide) in Greater China

Shanghai, September 18, 2019 /PRNewswire/ -- AstraZeneca announced today that it has entered into an agreement with Ironwood Pharmaceuticals, Inc. regarding Linzess^®(Linaclotide) The cooperation agreement has been revised and a consensus reached. According to the latest agreement, AstraZeneca obtains exclusive rights for the development, production, and commercialization of linaclotide in mainland China, Hong Kong, and Macau.

Under the revised collaboration agreement, AstraZeneca will be solely responsible for Linzess in the aforementioned regions^®development, manufacturing, and commercialization. Ironwood will no longer be involved in the above-mentioned regions for Linzess^®ofDevelopmentcommercialization, and will hand over drug manufacturing to AstraZeneca. The two companies first entered into a partnership in 2012 to jointly develop Linzess^®development and commercialization in China, while local operational execution is primarily handled by AstraZeneca.

“Since launching the world’s first proton pump inhibitor in China in 1993, AstraZeneca has been deeply committed to the field of gastroenterology in China for 26 years. The introduction of linaclotide into China not only fills the therapeutic gap for constipation-predominant irritable bowel syndrome (IBS-C) in our country, but also serves as another testament to AstraZeneca’s ongoing commitment to Chinese patients. We believe that linaclotide will usher in a new chapter in the treatment of IBS-C in China.””Lei Wang, Executive Vice President of AstraZeneca and President of International Business and China, further stated, “In the future, we will continue to accelerate the introduction of globally leading medicines, enabling more Chinese patients with digestive diseases to receive timely treatment with innovative drugs.””

“AstraZeneca has extensive experience and strong capabilities in the development and commercialization of pharmaceuticals in China.”Ironwood CEO Mark Mallon stated:“Approximately 14 million adults in China alone suffer from constipation-predominant irritable bowel syndrome, and we believe AstraZeneca isLinaclotideExcellent partners for these patients.”

Linaclotide, the world’s first guanylate cyclase agonist, was approved by the National Medical Products Administration in January 2019 for the treatment of irritable bowel syndrome with constipation (IBS-C) in adults and is poised for commercial launch in mainland China.

In ChinaAt least 14 million patients in China suffer from IBS-C^[1], significantly affecting patients' work and quality of life. Linaclotide’s 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 irritable bowel syndrome with constipation (IBS-C). Phase III clinical trials in China demonstrated that, compared with placebo, more than 60% of patients achieved spontaneous bowel movements within one day of starting linaclotide treatment.^[2]; 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.^[4]。

Regarding Payment Terms in the Agreement

From 2021 to 2024, AstraZeneca will make fixed payments totaling $35 million to Ironwood in three installments. In addition, Ironwood is eligible to receive milestone payments of up to $90 million upon achievement of predefined sales targets. According to Linzess^®In mainland China, Hong Kong, and Macau, Ironwood will also be eligible to receive a floating percentage royalty based on annual net sales. In these regions, Ironwood will no longer co-share the costs for Linzess.^®development and commercialization costs, nor will it share in sales profits.

On Constipation-Predominant Irritable Bowel Syndrome (IBS-C)

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 IBS-C accounting for 15% of cases.^[3]. Currently, there are no targeted and effective therapeutic drugs for IBS-C in China.^[4], treatment primarily involves selecting appropriate medications based on symptoms, such as antispasmodics and osmotic laxatives. Studies have shown that over 40% of patients are dissatisfied with their treatment.

About Linaclotide

Linaclotide is a guanylate cyclase-C agonist, an innovative drug recommended by the American Gastroenterological Association (AGA) guidelines for the treatment of irritable bowel syndrome with constipation (IBS-C), and is also a standard medication for treating IBS-C (recommendation grade: strong; evidence level: 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%). Efficacy was evident as early as the first week of treatment, and symptoms continued to improve throughout the treatment period.^[6]. Furthermore, as linaclotide acts locally in the intestine with negligible systemic absorption, it exhibits 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.^[6]。

References
^[1] Zhang L, Duan LP, Liu YX, et al. Prevalence of irritable bowel syndrome and related risk factors 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]Gastrointestinal Functional Disorders Collaboration Group, Chinese Society of Gastroenterology, Chinese Medical Association. Chinese expert consensus on irritable bowel syndrome (2015, Shanghai) [J]. Chinese Journal of Digestion, 2016, 36(5): 299-312.
^[4]XiongLi Shou, Shi Quan, et al. Clinical Characteristics and Healthcare-Seeking Behavior of 123 Patients with Irritable Bowel Syndrome in a Gastroenterology Specialty Outpatient Clinic [J]. Chinese Journal of Digestion, July 2015, Vol. 35, No. 7
^[5] Weinberg DS, et al. Gastroenterology 2014;147(5):1146–1148.
^[6] Yang Y, et al. J Gastroenterol Hepatol. 2018