These data complement a pooled analysis of data from two, three-week placebo-controlled phase 3 studies of CBZ-ERC, which demonstrated that CBZ-ERC significantly reduced manic and mixed symptoms for patients and was generally well tolerated. CBZ-ERC, manufactured for Shire US Inc., is the only formulation of carbamazepine approved by the U.S. Food and Drug Administration for treatment of patients with acute manic and mixed episodes associated with Bipolar I Disorder. Shire provided funding for these studies.
“Many patients still fail to find an effective medication for their bipolar disorder that is generally well tolerated with a low incidence of weight gain, which can influence their ability to stay on treatment,” said Richard H. Weisler, M.D., primary investigator of both clinical trials and adjunct professor of psychiatry at UNC’s School of Medicine. “A medication like CBZ-ERC that works effectively and is well tolerated in both manic and mixed patients is a very important addition to our treatment options for patients and their doctors.”
Weisler also is an adjunct assistant professor of psychiatry and behavioral sciences at Duke University Medical Center and has a private practice in Raleigh.
As many as 450 million people suffer from a mental or behavioral disorder worldwide, according to the World Health Organization. A recent study demonstrated that Bipolar I Disorder is more prevalent in the U.S. than previously estimated, affecting approximately 2 percent of the population annually and 3.3 percent of the population in its lifetime. These estimates are conservative considering the difficulty in the diagnosis of bipolar disorder. In the United States, annual costs for prevalence-based bipolar disorder are estimated at $45.2 billion, while lifetime costs of incidence-based bipolar disorder amount to about $24 billion. Bipolar disorder, also known as manic depression, is an illness that causes a person to experience extreme mood changes that alternate between manic episodes of abnormally high energy and the severe lows of depression, often with periods of normal mood in between.
The six-month study was an open-label extension trial for 92 patients who previously participated in one of two large, three-week phase 3 studies in which investigators randomized a total of 263 hospitalized participants to receive either CBZ-ERC or a placebo, although neither investigators nor patients knew to which group a patient was assigned until the study ended.
Of the patients who had responded to CBZ-ERC treatment during the phase 3 trials, defined as a 50 percent decrease in scores of the Young Mania Rating Scale (YMRS), 78 percent remained responders in the extension study. Also, 73 percent of those previously on placebo responded during the extension study. Overall, only 11 (14.3 percent) of the 77 intent-to-treat study patients experienced a relapse while taking CBZ-ERC. These participants’ estimated average time to relapse was 141.8 ± 5.6 days.
Weisler and his coinvestigators also pooled and analyzed the data from the two earlier phase 3 studies, confirming previous findings that CBZ-ERC is effective and generally well tolerated in patients with Bipolar I Disorder with manic or mixed episodes.
When examining the 147 patients experiencing mixed episodes, the investigators found that CBZ-ERC treatment demonstrated significantly greater improvements in average YMRS scores compared to placebo (-12.39 versus –8.84, P<.01). Patients experiencing manic episodes taking CBZ-ERC also had significantly greater improvements in average YMRS scores versus the placebo group (–12.22 versus –5.02, P<.0001).
All of the patients, who ranged in age from 18 to 76 years, had a previous diagnosis of Bipolar I Disorder, with the most current episode manic or mixed, as defined in the Diagnostic and Statistical Manual for Mental Disorders, fourth edition, text revision (DSM-IV-TR®).
Treatment with CBZ-ERC was initiated at 200 milligrams (mg) twice daily and increased, as necessary and tolerated, by 200 mg per day up to 1,600 mg per day. Doses greater than 1,600 mg per day were not studied.
The most common adverse events reported in these studies associated with CBZ-ERC included dizziness, somnolence, nausea, vomiting, ataxia and pruritis. These events were generally mild and were most often reported early in dose titration. Adverse events in all studies were typical of those associated with CBZ.
Weisler’s co-authors for both studies were Dr. R. Hirschfeld of the University of Texas Medical Branch at Galveston, Dr. A. J. Cutler of the University of South Florida, Dr. T. Gazda of St. Luke’s Medical Center, Dr. T. Ketter of Stanford University School of Medicine; Dr. P Keck, Jr. of the University of Cincinnati College of Medicine, Cincinnati, Ohio; Dr. A. Swann of the University of Texas Medical School at Houston; and Dr. A. Kalali of Quintiles CNS Therapeutics in San Diego.
Footnotes:
i) “Investing in mental health,” The Department of Mental Health and Substance Dependence, Noncommunicable Diseases and Mental Health, World Health Organization, Geneva. 2003. ISBN 92 4 156257 9 Accessed at http://www.who.int/mental_health/media/en/investing_mnh.pdf on Nov. 29, 2004.
ii) Bridget F et al. Prevalence, Correlates, and Comorbidity of Bipolar I Disorder and Axis I and II Disorders: Results From the National Epidemiologic Survey on Alcohol and Related Conditions. J Clin Psychiatry 2005;66:1205-1215.
iii) Kleinman L, Lowin A, Flood E, et al. Costs of bipolar disorder. Pharmacoeconomics, 2003;21(9):601-22.
USPMHC#126
EFFICACY OF CARBAMAZEPINE EXTENDED-RELEASE CAPSULES IN BIPOLAR DISORDER: SHORT- AND LONG-TERM RESULTS
USPMHC#125
CARBAMAZEPINE EXTENDED-RELEASE CAPSULES FOR MIXED EPISODES IN BIPOLAR I DISORDER
About Bipolar Disorder
Bipolar Disorder is characterized by episodes of mania and depression, with periods of normal mood in between. The disorder can have devastating effects on an individual’s life, although proper diagnosis and early treatment can usually alter the course of the illness.
Because of the severity of the illness, bipolar disorder is disruptive to patients, their families, friends and colleagues and can damage relationships, cause poor job or school performance and suicide. Although bipolar disorder is not curable, it is treatable and recovery is possible. Early diagnosis combined with drug therapy is key to optimal treatment.
Important Safety Information
EQUETRO™ contains carbamazepine. If you are currently taking another medication that contains carbamazepine, do not begin taking Equetro without discussing this with your healthcare provider.
If you are taking any other medications, including oral contraceptives, over-the-counter medications, or herbal products, be sure to inform your healthcare provider as Equetro can interact with other medications.
Equetro was generally well tolerated in clinical studies. The most common side effects, particularly when first starting on Equetro, were dizziness, drowsiness, unsteadiness, nausea, and vomiting.
Contact your healthcare provider if you have any unexplained bruising, fever, or infection. Products that contain carbamazepine have been associated with rare but serious types of blood disorders.
People with bipolar disorder have an increased risk for suicide. It is important to discuss risk factors for suicide with your healthcare provider. If you are experiencing these risk factors, it is important to contact your healthcare provider immediately or seek emergency care.
Please see complete Prescribing Information at www.equetro.com.
For further information please contact:
Investor Relations
Cléa Rosenfeld (UK and Europe), 44-125-689-4160
Brian Piper (US and Canada), 484-595-8252
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Jessica Mann (UK and Europe), 44-125-689-4280
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Notes to editors:
Shire Pharmaceuticals Inc.
Shire Pharmaceuticals Inc. is a US subsidiary of Shire Pharmaceuticals Group plc. Shire’s strategic goal is to become the leading specialty pharmaceutical company that focuses on meeting the needs of the specialist physician. Shire focuses its business on central nervous system (CNS), gastrointestinal (GI), general products (GP) and human genetic therapies (HGT) - all being areas in which Shire has a commercial presence. The structure is sufficiently flexible to allow Shire to target new therapeutic areas to the extent opportunities arise through acquisitions. Shire believes that a carefully selected portfolio of products with a strategically aligned and relatively small-scale sales force will deliver strong results.
Shire’s focused strategy is to develop and market products for specialty physicians. This approach aims to deliver increased returns and lower risks. Shire’s in-licensing and merger and acquisition efforts are focused on products in niche markets with strong intellectual property protection either in the US or Europe.
For further information on Shire, please visit the Company’s website: www.shire.com.
"SAFE HARBOR" STATEMENT UNDER THE PRIVATE SECURITIES LITIGATION REFORM ACT OF 1995
Statements included herein that are not historical facts are forward-looking statements. Such forward-looking statements involve a number of risks and uncertainties and are subject to change at any time. In the event such risks or uncertainties materialize, Shire's results could be materially affected. The risks and uncertainties include, but are not limited to, risks associated with: the inherent uncertainty of pharmaceutical research, product development, manufacturing and commercialization; the impact of competitive products, including, but not limited to, the impact of those on Shire's Attention Deficit and Hyperactivity Disorder (ADHD) franchise; patents, including, but not limited to, legal challenges relating to Shire's ADHD franchise; government regulation and approval, including, but not limited to, the expected product approval dates of DAYTRANA™ (MTS/METHYPATCH™) (ADHD), SPD503 (ADHD), SPD465 (ADHD), MESAVANCE™ (SPD476) (ulcerative colitis), I2S (iduronate-2-sulfatase) (Hunter syndrome), and NRP104 (ADHD), including its scheduling classification by the Drug Enforcement Administration in the United States; Shire’s ability to benefit from its acquisition of Transkaryotic Therapies, Inc.; Shire's ability to secure new products for commercialization and/or development; and other risks and uncertainties detailed from time to time in Shire's filings with the Securities and Exchange Commission, including its Annual Report on Form 10-K for the year to December 31, 2004.
i “Investing in mental health,” The Department of Mental Health and Substance Dependence, Noncommunicable Diseases and Mental Health, World Health Organization, Geneva. 2003. ISBN 92 4 156257 9 Accessed at http://www.who.int/mental_health/media/en/investing_mnh.pdf on Nov. 29, 2004.
ii Bridget F et al. Prevalence, Correlates, and Comorbidity of Bipolar I Disorder and Axis I and II Disorders: Results From the National Epidemiologic Survey on Alcohol and Related Conditions. J Clin Psychiatry 2005;66:1205-1215.
iii Kleinman L, Lowin A, Flood E, et al. Costs of bipolar disorder. Pharmacoeconomics, 2003;21(9):601-22.