Phase IIb Data Show Once-Daily Naldemedine Provides Significant Improvement For Patients With Opioid-Induced Constipation

FLORHAM PARK, N.J., May 19, 2015 /PRNewswire/ -- Shionogi Inc. today announced data from a Phase IIb study that showed 0.2 mg and 0.4 mg of naldemedine demonstrated statistically significant efficacy in treating opioid-induced constipation (OIC) in patients with chronic non-cancer pain. Naldemedine is an investigational, oral, peripherally acting mu-opioid receptor antagonist (PAMORA). The data, which are being presented today as a late-breaker (abstract #901e) at the Digestive Disease Week meeting in Washington, D.C., also showed that naldemedine was generally well-tolerated at both doses. Naldemedine is currently being evaluated in multiple Phase III studies.

"Opioid-induced constipation is the most commonly reported side effect of chronic opioid therapy, and can severely impact a patient's health and well-being," said Lynn Webster, MD, Vice President of Scientific Affairs, PRA Health Sciences and an investigator participating in the study. "The results of this study are encouraging for patients with OIC."

About the Study
A total of 244 patients with chronic non-cancer pain with OIC were randomized to receive naldemedine once daily (0.1mg, 0.2mg, 0.4mg), or a placebo (PBO) for four weeks. Patients had received opioid treatment for at least three months prior to the study, and had less than three spontaneous bowel movements (SBM) per week during the screening period. The primary efficacy endpoint for the study was change from baseline in the frequency of SBM per week to the last two weeks of the treatment period.  Results showed a statistically significant improvement in the primary efficacy endpoint (SBM) for patients using naldemedine at doses of 0.2mg (3.37 SBM; p=0.0014 vs PBO) and 0.4mg (3.64 SBM; p=0.0003 vs PBO) versus placebo (1.42 SBM).

The secondary efficacy endpoint measured the proportion of patients in the last two weeks of the study period with at least three SBM per week and an increase of more than one SBM per week compared to baseline. More than half of all naldemedine patients in the trial responded (0.1mg dose = 52.5 percent; 0.2mg dose = 71.2 percent; 0.4 mg dose = 66.7 percent) compared to patients taking placebo (39 percent). Naldemedine was generally well-tolerated at all doses with the most commonly reported side effects being gastrointestinal disorders such as abdominal pain, diarrhea, flatulence and nausea.

About Opioid-Induced Constipation (OIC)
Opioid-induced constipation is characterized by any of the following: reduced bowel movement frequency, development or worsening of straining to pass bowel movements, a sense of incomplete rectal evacuation, or harder stool consistency.¹ It is estimated that 40-50 percent of chronic opioid patients, about 11 million Americans, experience opioid-induced constipation, with fewer than half reporting satisfactory results with laxatives.² Managing OIC and its clinical consequences places a significant financial burden on the healthcare system and the patient.

About Shionogi Inc.
Shionogi Inc. is the U.S.-based subsidiary of Shionogi & Co., Ltd., a Japanese pharmaceutical company with a 137-year history discovering and developing innovative therapies. Shionogi Inc. continues this focus on the development and commercialization of high quality medicines that protect the health and well-being of the patients we serve. The company currently markets products in several therapeutic areas including women's health, anti-infectives, pain and cardiovascular diseases. Our pipeline is focused on infectious disease, pain, CNS, and oncology. For more details, visit www.shionogi.com. For more information on Shionogi & Co., Ltd., visit www.shionogi.co.jp.

Forward Looking Statement
This announcement contains forward-looking statements. These statements are based on expectations in light of the information currently available, assumptions that are subject to risks and uncertainties which could cause actual results to differ materially from these statements. Risks and uncertainties include general domestic and international economic conditions such as general industry and market conditions, and changes of interest rate and currency exchange rate. These risks and uncertainties particularly apply with respect to product-related forward-looking statements. Product risks and uncertainties include, but are not limited to, completion and discontinuation of clinical trials; obtaining regulatory approvals; claims and concerns about product safety and efficacy; technological advances; adverse outcome of important litigation; domestic and foreign healthcare reforms and changes of laws and regulations. Also for existing products, there are manufacturing and marketing risks, which include, but are not limited to, inability to build production capacity to meet demand, unavailability of raw materials and entry of competitive products. The company disclaims any intention or obligation to update or revise any forward-looking statements whether as a result of new information, future events or otherwise.

¹ Camilleri. M, Drossman D.A., Becker G.,Webster L.R., Davies A.N., Mawe G.M. Emerging treatments in neurogastroenterology: a multidisciplinary working group consensus statement on opioid-induced constipation. Neurogastroenterology Motil. 2014. 26, 1386-1395  
² Pappagallo M. Incidence, Prevalence, and Management of Opioid Bowel Dysfunction. The American Journal of Surgery. 182 (Suppl to November 2001) 11s-18s

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SOURCE Shionogi Inc.

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