Tokyo, December 19, 2016 - Astellas Pharma Inc. (TSE: 4503, President and CEO: Yoshihiko Hatanaka, “Astellas”) announced that it obtained a marketing approval for a guanylate cyclase-C (GC-C) receptor agonist, LINZESS® (generic name: linaclotide Development Code: ASP0456) for irritable bowel syndrome with constipation1) (IBS-C) in adults by the Ministry of Health, Labour and Welfare in Japan today.
Astellas expects that obtaining marketing approval of LINZESS® will help patients who are suffering from IBS-C by providing a new therapeutic option.
The approval was obtained based mainly on the results from the double-blind, placebo-controlled, parallel-group comparative study in Phase III conducted in Japan in adults with IBS-C. This study randomized 500 adults with IBS-C in Japan. Patients were randomized 1:1 to receive either 500 mcg of LINZESS® or placebo for 12 weeks to examine clinical efficacy and safety of LINZESS®. The data indicates that patients treated with LINZESS® showed statistically significant improvement compared to placebo-treated patients for both co-primary endpoints. Regarding the first primary endpoint, 34% of patients treated with LINZESS® were Global Assessment of Relief of IBS Symptoms Responders, compared to 18% of placebo-treated patients (p<0.001). Regarding the second primary endpoint, 35% of patients treated with LINZESS® were Complete Spontaneous Bowel Movement (CSBM) Overall Responders, compared to 19% of placebo-treated patients (p<0.001). Additionally, improvements were achieved in pre-specified secondary endpoints in this trial covering abdominal and constipation symptoms, including bloating and abdominal pain/discomfort. Diarrhea rates in this trial were 9.6% for LINZESS® vs. 0.4% for placebo; all cases of diarrhea were characterized as mild or moderate in severity.
Upon this approval in Japan, Astellas will make the milestone payment of US $15 million to Ironwood, which has immaterial impact on Astellas’ consolidated full-year business forecasts for the fiscal year ending March 31, 2017.
Date of Approval: December 19, 2016
Brand Name: LINZESS®
Generic Name: linaclotide
Dosage Form/Content:Tablet containing 0.25 mg of linaclotide
Indication:Irritable bowel syndrome with constipation
Precautions with related to indication:
Application of this drug should be considered for adult patients whose symptom has not improved after dietary guidance and lifestyle guidance as the basics of the treatment for Irritable bowel syndrome with constipation are provided.
Dosage and Administration:
The usual adult dosage is 0.5 mg as linaclotide taken orally once daily before eating.
The dosage may be reduced to 0.25 mg depending on the symptoms.
Precautions with related to dosage and administration:
Since occurrence of severe diarrhea is possible, investigators are instructed to evaluate patients’ symptoms periodically so that continuous administration of this drug will not be done unthinkingly.
LINZESS® is a GC-C receptor agonist. LINZESS® locally binds to the GC-C receptor expressed on the intestinal epithelium. Activation of the GC-C receptor results in improved visceral hypersensitivity, increased intestinal fluid secretion and accelerated intestinal transit. LINZESS® is approved for treatment of adults with IBS-C or chronic idiopathic constipation (CIC) and available in more than 30 countries. It is estimated that 2.9% of adults in Japan suffer from IBS-C 2), and, until today, there were no prescription products currently approved in Japan for the treatment of this indication. Astellas entered into a license agreement with Ironwood Pharmaceuticals, Inc. (NASDAQ: IRWD, CEO: Peter Hecht, Ph.D., “Ironwood”) in 2009 and Ironwood granted Astellas exclusive rights to develop and commercialize LINZESS® Tablets in Japan.
1) Irritable bowel syndrome (IBS) is a functional but not organic disorder which causes abdominal pain and/or discomfort with abnormal defecation including diarrhea and constipation. These gastrointestinal symptoms persist for a long period with frequent remissions and exacerbations. Abdominal pain/discomfort and abnormal defecation are often associated with various factors such as stress, which is considered to cause hypersensitivity of the enteric nervous system.
2) Kubo M, Fujiwara Y, Shiba M, Kohata Y, Yamagami H, Tanigawa T, et al. Differences between risk factors among irritable bowel syndrome subtypes in Japanese adults. Neurogastroenterol Motil. 2011;23:249-54.