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Takeda and Sucampo Report Top-Line Results of Two Phase 3 Trials of Lubiprostone in Opioid-Induced Bowel Dysfunction

BETHESDA, Md.--(BUSINESS WIRE)--Jul 21, 2009 - Sucampo Pharma Americas, Inc., a wholly owned subsidiary of Sucampo Pharmaceuticals, Inc. (NASDAQ:SCMP) and Takeda Pharmaceuticals North America, Inc., today announced top-line results from two identically-designed phase 3 clinical trials of lubiprostone (24 mcg, twice daily) for the management of opioid-induced bowel dysfunction (OBD) in subjects with chronic, non-cancer pain.

In study OBD0631 (“631”), the primary endpoint of a statistically significant change from baseline in the frequency of spontaneous bowel movements (SBMs) at Week 8 of treatment was met when lubiprostone was compared to placebo. Additionally, statistical significance was achieved for eight of the twelve secondary endpoints, including key symptoms associated with OBD. Study OBD0632 (“632”) did not achieve statistical significance for the same primary endpoint. Statistically significant improvements with lubiprostone were achieved for two of the secondary endpoints and positive trends were observed in four of the other secondary endpoints. Subjects treated with lubiprostone showed a statistically significant increase in the frequency of SBMs at Week 8 from their baseline, from 1.42 to 4.54 SBMs in the 631 trial and from 1.60 to 4.10 SBMs in the 632 trial. The increase for placebo over their baseline was from 1.46 to 3.81 SBMs for the 631 trial and 1.60 to 3.95 SBMs for the 632 trial.

There was a high rate of response in the placebo arm of the 632 trial. Approximately 58 percent of subjects treated with placebo in the 632 trial experienced more than three SBMs per week during each week of the trial.

In both trials, a post-hoc sub-analysis showed that subjects on methadone treatment regimens who were randomized to receive lubiprostone showed a lower SBM response when compared to lubiprostone patients treated with other opioid medications. Additionally, in the 631 and 632 trials methadone subjects treated with lubiprostone did not show improvement in OBD symptomatic endpoints while lubiprostone subjects treated with other opioids showed statistically significant improvement in both studies in abdominal discomfort/pain, constipation severity, stool consistency and straining over the placebo.

The overall adverse event rate for the combined trials was 54.9 percent for lubiprostone and 51.6 percent for placebo. The most common adverse events were nausea, 15 percent for lubiprostone vs. 7.5 percent for placebo, and diarrhea, 8.5 percent for lubiprostone vs. 3.7 percent for placebo.

Gayle Dolecek, Senior Vice President, Research & Development at Sucampo, said, “Given the results in the two studies, we are continuing further analysis of the data. However, these results suggest that lubiprostone may have the potential to treat the symptoms of OBD, for which there is currently no approved drug.”

Sucampo also announced they will continue the ongoing, fully-enrolled, long-term, follow-on, open-label safety study of lubiprostone in OBD subjects with chronic, non-cancer pain. In this study, a total of 445 patients are receiving one 24-mcg gel capsule of lubiprostone twice a day for nine months. Data from this study are expected in late 2009. If this follow-on study concludes successfully, these data are anticipated to be submitted to FDA in 2010.

About the 631 and 632 trials

A total of 875 OBD subjects (excluding those with cancer-related pain) at 187 sites in the U.S. and Canada were randomized into two identically designed 12-week, double-blind, placebo-controlled phase 3 trials and received one 24-mcg gel capsule of lubiprostone twice a day for 12 weeks. Subjects in the trial were administered different opioid pain medications including morphine, methadone, oxycontin and fentanyl. Inclusion criteria required subjects to be on opioid medications for at least 30 days prior to screening and continue to use that medication during the trial period and also required that patients have fewer than three SBMs per week during the two-week screening period before randomization into the treatment portion of the trial.

Opioid-induced Bowel Dysfunction (OBD)

Opioid-induced Bowel Dysfunction (OBD) comprises a variety of gastrointestinal conditions inclusive of severe constipation brought on by the use of narcotic medications such as morphine and codeine, which are commonly referred to as opioids. Unlike opioid-induced constipation, OBD is a constellation of adverse gastrointestinal effects characterized by infrequent and incomplete bowel movements, hard stool consistency, straining associated with bowel movements and abdominal discomfort/pain and bloating. In addition to a delay in intestinal transit, the reduction in secretion, upregulation of water and absorption of electrolytes in the gut may contribute to the constipating effects of opioids.

Physicians prescribe opioids for patients with advanced medical illnesses as well as those undergoing surgery. Despite their pain-relieving effectiveness, opioids are known to produce gastrointestinal effects that lead to opioid-induced constipation, including inhibition of large intestine motility, decreased gastric emptying and hard stools. Currently, there are no FDA-approved products that are indicated for treatment of OBD. As a result, patients frequently must discontinue opioid therapy and endure pain in order to obtain relief from opioid-induced bowel dysfunction.

According to the American Pain Foundation, over 50 million Americans suffer from chronic pain and nearly 25 million Americans experience acute pain each year due to injuries or surgery. Opioid pain relievers are widely prescribed for these patients, many of whom also develop OBD. We believe over three million people in the U.S. have some form of OBD.

AMITIZA® (lubiprostone) for Chronic Idiopathic Constipation in Adults and Irritable Bowel Syndrome with Constipation in Adult Women

AMITIZA is a local activator of type-2 chloride channels in cells lining the small intestine. AMITIZA increases fluid secretion into the intestinal tract. This increased fluid level softens the stool, facilitating intestinal motility and bowel movements. The type 2 chloride channels also play an important role in the restoration of tight junction complexes and in the recovery of barrier function in the body.

AMITIZA (lubiprostone) is indicated for the treatment of Chronic Idiopathic Constipation (24 mcg twice daily) in adults and for Irritable Bowel Syndrome with Constipation (8 mcg twice daily) in women ‰¥18 years of age and older.

AMITIZA is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction. Patients with symptoms suggestive of mechanical gastrointestinal obstruction should be thoroughly evaluated by the treating healthcare provider to confirm the absence of such an obstruction prior to initiating AMITIZA treatment.

The safety of AMITIZA in pregnancy has not been evaluated in humans. AMITIZA should be used during pregnancy only if the benefit justifies the potential risk to the fetus. Women who could become pregnant should have a negative pregnancy test prior to beginning therapy with AMITIZA and should be capable of complying with effective contraceptive measures.

Patients taking AMITIZA may experience nausea. If this occurs, concomitant administration of food with AMITIZA may reduce symptoms of nausea. Patients who experience severe nausea should inform their healthcare provider.

AMITIZA should not be prescribed to patients that have severe diarrhea. Patients should be aware of the possible occurrence of diarrhea during treatment and inform their healthcare provider if the diarrhea becomes severe.

Patients taking AMITIZA may experience dyspnea within an hour of first dose. This symptom generally resolves within three hours, but may recur with repeat dosing. Patients who experience dyspnea should inform their healthcare provider. Some patients have discontinued therapy because of dyspnea.

In clinical trials of AMITIZA (24 mcg twice daily vs. placebo: N=1113 vs. N=316) in patients with Chronic Idiopathic Constipation, the most common adverse reactions (incidence >4%) were nausea (29% vs. 3%), diarrhea (12% vs. 1%), headache (11% vs. 5%), abdominal pain (8% vs. 3%), abdominal distention (6% vs. 2%), and flatulence (6% vs. 2%).

In clinical trials of AMITIZA (8 mcg twice daily vs. placebo: N=1011 vs. N=435) in patients with Irritable Bowel Syndrome with Constipation, the most common adverse reactions (incidence >4%) were nausea (8% vs. 4%), diarrhea (7% vs. 4%), and abdominal pain (5% vs. 5%).

Please see complete Prescribing Information at www.amitiza.com.

Amitiza® is co-marketed in the U.S. by Sucampo Pharmaceuticals, Inc. and Takeda Pharmaceuticals North America, Inc.

Takeda Pharmaceuticals North America, Inc. and Takeda Global Research & Development Center, Inc.

Based in Deerfield, Ill., Takeda Pharmaceuticals North America, Inc. and Takeda Global Research & Development Center, Inc. are subsidiaries of Takeda Pharmaceutical Company Limited, the largest pharmaceutical company in Japan. The respective companies currently market oral diabetes, insomnia, rheumatology and gastroenterology treatments and seek to bring innovative products to patients through a pipeline that includes compounds in development for diabetes, cardiovascular disease, oncology, gastroenterology, neurology and other conditions. Takeda is committed to striving toward better health for individuals and progress in medicine by developing superior pharmaceutical products. To learn more about these Takeda companies, visit www.tpna.com.

Sucampo Pharmaceuticals

Sucampo Pharmaceuticals, Inc., an international biopharmaceutical company based in Bethesda, Maryland, focuses on the development and commercialization of medicines based on prostones. The therapeutic potential of prostones, which are bio-lipids that occur naturally in the human body, was first identified by Ryuji Ueno, M.D., Ph.D., Ph.D., Sucampo Pharmaceuticals' Chairman and Chief Executive Officer. Dr. Ueno founded Sucampo Pharmaceuticals in 1996 with Sachiko Kuno, Ph.D., founding Chief Executive Officer and currently Advisor, International Business Development.

Sucampo is marketing Amitiza (lubiprostone) 24 mcg in the U.S. for Chronic Idiopathic Constipation in adults and Amitiza 8 mcg in the U.S. to treat Irritable Bowel Syndrome with Constipation in adult women. Sucampo also is developing the drug for additional gastrointestinal disorders with large potential markets. In April 2009, Sucampo acquired U.S. and Canadian rights to Rescula®, an FDA-approved treatment for open-angle glaucoma and ocular hypertension. Sucampo plans to re-launch Rescula in 2010, and to develop it for additional ophthalmic indications. In addition, Sucampo has a robust pipeline of compounds with the potential to target underserved diseases affecting millions of patients worldwide. Sucampo Pharmaceuticals, Inc. has three wholly owned subsidiaries: Sucampo Pharma Europe, Ltd., located in the UK; Sucampo Pharma, Ltd., located in Japan; and, Sucampo Pharma Americas, Inc., located in Maryland. To learn more about Sucampo Pharmaceuticals and its products, visit www.sucampo.com.

Amitiza is a registered trademark of Sucampo Pharmaceuticals, Inc. and Rescula is a registered trademark used under license.

Forward-Looking Statements

Any statements in this press release about future expectations, plans and prospects for Sucampo Pharmaceuticals are forward-looking statements made under the provisions of The Private Securities Litigation Reform Act of 1995. Forward-looking statements may be identified by the words “project,” “believe,” “anticipate,” “plan,” “expect,” “estimate,” “intend,” “should,” “would,” “could,” “will,” ”may” or other similar expressions. Forward-looking statements include statements about the potential utility of Amitiza and Rescula to treat particular indications and expected data availability dates. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including those described in Sucampo Pharmaceuticals' filings with the Securities and Exchange Commission (SEC), including the annual report on Form 10-K for the year ended December 31, 2008 and other periodic reports filed with the SEC. Any forward-looking statements in this press release represent Sucampo Pharmaceuticals' views only as of the date of this release and should not be relied upon as representing its views as of any subsequent date. Sucampo Pharmaceuticals anticipates that subsequent events and developments will cause its views to change. However, while Sucampo Pharmaceuticals may elect to update these forward-looking statements publicly at some point in the future, Sucampo Pharmaceuticals specifically disclaims any obligation to do so, whether as a result of new information, future events or otherwise.

 

Contact: Sucampo Pharmaceuticals, Inc.
Kate de Santis, 240-223-3834
kdesantis@sucampo.com
or
Westwicke Partners
John Woolford, 410-213-0506
john.woolford@westwicke.com
or
Takeda Pharmaceuticals North America
Elissa J. Johnsen, 224-554-3185
ejohnsen@tpna.com

 

Posted: July 2009

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