– Ironwood to receive up to $125 million, consisting of $35 million in non-contingent payments and up to $90 million in commercial milestones, in addition to tiered royalties up to 20 percent –
– AstraZeneca obtains full responsibility for the development, manufacturing and commercialization of LINZESS in China –
CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Ironwood Pharmaceuticals, Inc. (NASDAQ: IRWD), a GI healthcare company, announced today that it has amended its collaboration agreement with AstraZeneca for the development and commercialization of LINZESS in China. LINZESS was approved by the National Medical Products Administration for adults with IBS-C in China in January 2019. LINZESS is expected to be launched in China in the second half of 2019.
Under the terms of the amended agreement, AstraZeneca will obtain exclusive rights to develop, manufacture and commercialize linaclotide in China (including Hong Kong and Macau) and will be responsible for all expenses associated with these activities. In return, Ironwood will receive up to a total of $125 million, including non-contingent payments totaling $35 million paid in three installments through 2024 and up to $90 million in commercial milestone payments contingent on the achievement of certain net sales targets. Additionally, Ironwood will receive royalties beginning in the mid-single-digit percent and increasing up to 20 percent based on annual net sales of LINZESS in China. In connection with the amended agreement, Ironwood will no longer be jointly funding the development and commercialization of linaclotide or sharing in the net profit from sales in China.
Mark Mallon, chief executive officer of Ironwood, stated, “This amended collaboration – combined with our recent amendment to our Astellas agreement – reflects our continued strategy to focus our efforts in the U.S., thereby streamlining our business while enabling strong partners to bring linaclotide to patients worldwide. AstraZeneca has substantial experience and capabilities in developing and commercializing medicines in China. There are approximately 14 million adults suffering from IBS-C in China, and we believe AstraZeneca is well-positioned to bring LINZESS to these patients.”
The original collaboration between Ironwood and AstraZeneca for linaclotide was established in 2012. Linaclotide is available for the treatment of adults with IBS-C or chronic idiopathic constipation (CIC) in the United States and more than 30 other countries.
About linaclotide 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). Linaclotide is marketed by Allergan for the treatment of adults with moderate to severe IBS-C in Europe under the brand name CONSTELLA®. AstraZeneca has the exclusive rights to develop and commercialize linaclotide in China (including Hong Kong and Macau). Astellas has the exclusive rights to develop and commercialize linaclotide in Japan. Allergan has rights to develop and market in the rest of the world countries.
Important Safety Information
INDICATIONS AND USAGE LINZESS (linaclotide) is indicated in adults for the treatment of both irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC).
IMPORTANT SAFETY INFORMATION
WARNING: RISK OF SERIOUS DEHYDRATION IN PEDIATRIC PATIENTS LINZESS is contraindicated in patients less than 6 years of age. In nonclinical studies in neonatal mice, administration of a single, clinically relevant adult oral dose of linaclotide caused deaths due to dehydration. Use of LINZESS should be avoided in patients 6 years to less than 18 years of age. The safety and effectiveness of LINZESS have not been established in patients less than 18 years of age. |
Contraindications
- LINZESS is contraindicated in patients less than 6 years of age due to the risk of serious dehydration.
- LINZESS is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction.
Warnings and Precautions Pediatric Risk
- LINZESS is contraindicated in patients less than 6 years of age. The safety and effectiveness of LINZESS in patients less than 18 years of age have not been established. In neonatal mice, linaclotide increased fluid secretion as a consequence of GC-C agonism resulting in mortality within the first 24 hours due to dehydration. Due to increased intestinal expression of GC-C, patients less than 6 years of age may be more likely than patients 6 years of age and older to develop severe diarrhea and its potentially serious consequences.
- Use of LINZESS should be avoided in pediatric patients 6 years to less than 18 years of age. Although there were no deaths in older juvenile mice, given the deaths in young juvenile mice and the lack of clinical safety and efficacy data in pediatric patients, use of LINZESS should be avoided in pediatric patients 6 years to less than 18 years of age.
Diarrhea
- Diarrhea was the most common adverse reaction in LINZESS-treated patients in the pooled IBS-C and CIC double-blind placebo-controlled trials. The incidence of diarrhea was similar in the IBS-C and CIC populations. Severe diarrhea was reported in 2% of 145 mcg and 290 mcg LINZESS-treated patients, and in