Data Demonstrate Aripiprazole Significantly Improved Symptoms Of Acute Mania in
`Patients With Bipolar Disorder; New Data Presented Today at American Psychiatric
`Association Annual Meeting
`PR Newswire
`May 22, 2002 Wednesday
`
`Copyright 2002 PR Newswire Association, Inc.
`Distribution: TO MEDICAL AND BUSINESS EDITORS
`Section: FINANCIAL NEWS
`Length: 1238 words
`Dateline: PRINCETON, N.J. and TOKYO May 22
`
`Body
`
`Patients with bipolar disorder who received treatment with aripiprazole, an investigational antipsychotic
`medication, showed significant improvement in symptoms of acute mania, according to a new study
`presented today at the 155th Annual Meeting of the American Psychiatric Association. The placebo-
`controlled study also showed that aripiprazole has a rapid onset of action, significantly reducing
`symptoms of acute mania by day four of treatment. Aripiprazole was well tolerated, with discontinuations
`of therapy due to adverse events similar to placebo. Additionally, there was no significant difference in
`the incidence of clinically meaningful weight change in patients treated with aripiprazole and placebo.
`
`"In this study, aripiprazole demonstrated rapid onset of symptom improvement, which is very important
`when treating manic episodes," according to lead investigator Paul E. Keck, Jr., MD, Department of
`Psychiatry, University of Cincinnati College of Medicine. "We look forward to more data in the treatment
`of bipolar mania."
`
`Aripiprazole was studied in a Phase III multicenter, double-blind, randomized, placebo-controlled study
`with 262 patients diagnosed with acute mania. Beginning at day four, aripiprazole was significantly better
`than placebo in reducing acute manic symptoms, such as elevated mood, irritability, thought disorder,
`abnormal thought content and disruptive-aggressive behavior (p=0.004). This separation increased during
`the three-week treatment period as measured by mean change from baseline in the total score on the
`Young Mania Rating Scale (Y-MRS) (week three Y-MRS total score decreased by 8.15 and 3.35 for
`aripiprazole and placebo respectively, p=0.002). Furthermore, 40 percent of patients treated with
`aripiprazole responded to treatment, compared to 19 percent of patients treated with placebo (p=0.001). In
`this study, response was defined as a decrease of greater than or equal to 50 percent in Y-MRS total score.
`In a second placebo-controlled study, aripiprazole demonstrated symptom improvement comparable to
`that of the study previously described; however, due to a high placebo response rate (approximately 40
`percent), aripiprazole did not show statistical separation from placebo. The most commonly observed
`adverse events associated with aripiprazole were headache, nausea, dyspepsia, somnolence and agitation,
`whereas the most common adverse events associated with placebo were headache, agitation, nausea,
`dyspepsia and anxiety. The majority of somnolence and these gastrointestinal events occurred during the
`
`1 of 4
`
`Alkermes, Ex. 1028
`
`

`
`Data Demonstrate Aripiprazole Significantly Improved Symptoms Of Acute Mania in Patients With Bipolar Disorder;
`New Data Presented Today at American Psychiatric....
`
`first week of treatment and very few events lasted more than 7 days. Adverse events reported in the two
`studies were similar.
`
`"There are significant unmet needs in the treatment of serious mental illness," said Peter R. Dolan,
`Chairman and Chief Executive Officer, Bristol- Myers Squibb Company. "We are very encouraged by the
`clinical research being conducted with aripiprazole to help meet the needs of patients with psychiatric
`disorders."
`
`Bristol-Myers Squibb and Otsuka Pharmaceuticals filed regulatory applications for aripiprazole for an
`indication for treatment of schizophrenia in the U.S. and Europe in October and December 2001,
`respectively. The companies are currently conducting clinical
`trials with aripiprazole in psychotic
`illnesses such as schizophrenia, bipolar disorder and psychosis associated with Alzheimer's disease.
`
`Aripiprazole is believed to have a mechanism of action that is fundamentally different from available
`antipsychotics. Aripiprazole exhibits potent partial agonism of D2 dopamine receptors, and is also
`associated with partial agonism of 5HT(1A) serotonin receptors and antagonism of 5HT(2A) serotonin
`receptors. Partial agonism refers to the ability to both block a receptor if it is overstimulated and to
`stimulate a receptor when activity is needed.
`
`"We are proud to have discovered this compound," said Tatsuo Higuchi, President, Otsuka
`Pharmaceutical Co., Ltd. "We look forward to working with Bristol-Myers Squibb to developing
`aripiprazole to its fullest potential."
`
`Serious and Persistent Mental Illness
`
`Bipolar disorder, also known as manic-depressive disorder, affects nearly 2 million Americans, and like
`schizophrenia, generally strikes before the age of 30.(1) A person with bipolar disorder experiences mood
`episodes, which can include manic episodes, depressive episodes and mixed episodes.
`
`Manic episodes typically involve either extreme happiness or irritability accompanied by other changes in
`behavior, such as increased activity, decreased need for sleep, grandiose thinking and racing thoughts.
`During depressive episodes, individuals usually experience sadness, diminished interest in usual activities
`and disturbances in sleep, appetite, energy and concentration. Mixed episodes involve the simultaneous
`occurrence of depressive and manic symptoms. Sometimes individuals with bipolar disorder experience
`psychotic symptoms (such as delusions and hallucinations) during the mood episodes, but these psychotic
`symptoms go away as the episode resolves.
`
`The duration of mood episodes range from hours to many months. Between episodes, people with bipolar
`disorder often return to their usual level of functioning and may have minimal to no residual symptoms.
`Some people with the disorder can enjoy healthy, stable mood for many years between episodes, while
`others rapidly go in and out of mood episodes almost continually, while still others experience mood
`episodes at frequencies between these two extremes.(2)
`
`About Bristol-Myers Squibb and Otsuka Pharmaceutical Co., Ltd.
`
`Bristol-Myers Squibb Company and Otsuka Pharmaceutical Co., Ltd. are collaborative partners in the
`development and commercialization of aripiprazole in the United States and major European countries.
`Otsuka discovered aripiprazole.
`
`2 of 4
`
`Alkermes, Ex. 1028
`
`

`
`Data Demonstrate Aripiprazole Significantly Improved Symptoms Of Acute Mania in Patients With Bipolar Disorder;
`New Data Presented Today at American Psychiatric....
`
`Bristol-Myers Squibb is a $19 billion pharmaceutical and related health care products company whose
`mission is to extend and enhance human life.
`
`Founded 38 years ago, Otsuka Pharmaceuticals is a diversified health care company guided by its
`philosophy: "Otsuka, people creating new products for better health worldwide" and dedicated to the
`research and development of innovative medical, pharmaceutical, and nutritional consumer products to
`improve the quality of human life. Otsuka Pharmaceuticals has a diverse portfolio including central
`nervous system, cardiovascular, circulatory, gastro-intestinal, respiratory, dermatological, ophthalmologic,
`anti-cancer therapies, and is pursuing research in genomics and protein function. Otsuka is comprised of
`32 businesses and 19,000 employees around the world, earning total revenues of $4.5 billion annually.
`
`Upon regulatory approval, aripiprazole would be marketed worldwide by Otsuka Pharmaceuticals and
`Bristol-Myers Squibb. Aripiprazole was discovered by Otsuka Pharmaceutical Co., Ltd.
`
`Visit Bristol-Myers Squibb on the World Wide Web at: http://www.bms.com
`
`Visit Otsuka Pharmaceutical Co., Ltd. at: http://www.otsuka.co.jp
`
`(1) Symptoms & Causes of Manic Depression (Bipolar Disorder), National
`Mental Health Association website (http://www.healthtouch.com)
`
`(2) An Introduction to Bipolar Disorder, Johns Hopkins Medicine website
`(http://www.hopkinsmedicine.org)
`MAKE YOUR OPINION COUNT - Click Here
`http://tbutton.prnewswire.com/prn/11690X74656517
`
`SOURCE Bristol-Myers Squibb; Otsuka Pharmaceutical Co., Ltd.
`
`CONTACT: Tracy Furey, +1-609-252-3208, pager: +1-800-400-3216, tracy.furey@bms.com, or Jeff
`Macdonald, +1-609-252-5771, jeff.macdonald@bms.com, both of Bristol-Myers Squibb; Shinji Masaki of
`Otsuka Pharmaceutical Co., Ltd., +81-3-3292-0021, masakis@tky.otsuka.co.jp; or Debra Kaufmann of
`Otsuka America Pharmaceutical, Inc., +1-240-683-3568, debrak@otsuka.com
`http://www.prnewswire.com
`
`Classification
`Language: ENGLISH
`
`Publication-Type: Newswire
`
`Subject: MEDICAL RESEARCH (90%); PSYCHIATRY (90%); BIPOLAR DISORDER (90%);
`MENTAL ILLNESS (90%); DISEASES & DISORDERS (89%); MEDICAL TREATMENTS &
`PROCEDURES (89%); GASTROINTESTINAL DISORDERS (89%); ADVERSE DRUG EVENT
`REPORTING (78%); SCHIZOPHRENIA (78%); EXPERIMENTATION & RESEARCH (78%);
`ASSOCIATIONS & ORGANIZATIONS (77%); INVESTIGATIONS (74%); RESEARCH REPORTS
`(73%); TALKS & MEETINGS (72%); EXECUTIVES (50%); bc-NJ-Brstl-Myrs-Otsuka
`
`Company: BRISTOL-MYERS SQUIBB CO (81%); Bristol-Myers Squibb; Otsuka Pharmaceutical Co.,
`Ltd.; American Psychiatric Association
`
`3 of 4
`
`Alkermes, Ex. 1028
`
`

`
`Data Demonstrate Aripiprazole Significantly Improved Symptoms Of Acute Mania in Patients With Bipolar Disorder;
`New Data Presented Today at American Psychiatric....
`
`Organization: AMERICAN PSYCHIATRIC ASSOCIATION (93%); UNIVERSITY OF CINCINNATI
`(56%)
`
`Ticker: BMY (NYSE) (81%); BMY
`
`Industry: PSYCHIATRY (90%); PHARMACEUTICALS INDUSTRY (89%); ADVERSE DRUG
`EVENT REPORTING (78%); INVESTIGATIONAL DRUGS (74%); Medical; Pharmaceuticals; Health
`Care; Hospitals
`
`Person: JAMES L DOLAN (50%)
`
`Geographic: UNITED STATES (88%); New Jersey; Japan
`
`Load-Date: May 23, 2002
`
`4 of 4
`
`Alkermes, Ex. 1028