Long-Term Tolerability and Safety Data of Abilify(R) in Combination Treatment for Patients With Bipolar I Disorder

FLORENCE, Italy - Results Presented at the Annual Congress of the World Psychiatric Association (WPA)

ABILIFY(R) (aripiprazole), when used in combination with lithium or valproate, is a generally well-tolerated long-term treatment for patients with Bipolar I Disorder, who are partially non-responsive to lithium or valproate monotherapy.(1) The data presented at the annual congress for the World Psychiatric Association (WPA) report a favourable long-term safety profile for ABILIFY in combination with lithium or valproate.(1)

Professor Eduard Vieta, lead study investigator and Professor of Psychiatry and Director of the Bipolar Disorders Programme of the Hospital Clinic at the University of Barcelona, Spain, said “As a doctor, I value data on safety, tolerability and efficacy as extremely important. Clinicians look for treatments that are efficacious and tolerable in the long term. This study reports that aripiprazole can provide Bipolar I Disorder patients with a combination treatment option with the benefits of good long-term safety and tolerability.”

The efficacy and safety of ABILIFY, used in combination with lithium or valproate for the treatment of patients with Bipolar I Disorder, were investigated during a 6-week multicentre, double-blind, randomized, placebo-controlled study involving 348 patients, followed by a 46-week open-label extension phase.

In total, 283 patients entered the extension phase of the study, (prior placebo n=104 vs prior ABILIFY n=179).

The primary objective of the extension phase was to assess the long-term safety and tolerability of ABILIFY in combination with lithium or valproate. Patients in the study were followed up for an additional 46 weeks.

The open-label extension data, presented at the WPA congress, showed that ABILIFY, in combination with lithium or valproate, continued to be well-tolerated with no new or unexpected adverse side effects.

Evaluation of long-term efficacy was a secondary objective due to the open-label nature of the extension phase. Since there was no double-blind control, definitive statements regarding efficacy can not be made, but results support that improvements in bipolar symptoms were maintained through 52 weeks.(1)

The Young Mania Rating Scale (YMRS) Total Score and the Clinical Global Impressions-Bipolar-Severity of illness (CGI-BP-S) (Mania) Score continued to improve from the end of the double-blind phase to week 52.1 Specifically, the YMRS Total Score (Last Observation Carried Forward [LOCF]) continued to improve in both groups (-3.31 and -2.94 in patients receiving lithium and valproate, respectively.) CGI-BP-S (Mania) Score (LOCF) also improved in both groups (-0.39 and -0.57 in patients receiving lithium and valproate, respectively.)(1)

The results support previous clinical trials for ABILIFY, which demonstrated efficacy and safety and overall improved quality of life in patients with Bipolar I Disorder, when used as monotherapy. (2)(3)

Bipolar I Disorder is characterised by the occurrence of one or more Manic Episodes or Mixed Episodes. A Manic Episode is defined by a distinct period during which there is an abnormally and persistently elevated, expansive, or irritable mood. The mood disturbance must last for at least 1 week (unless hospitalisation is required).

A Mixed Episode is characterised by a period of time (lasting at least 1 week) in which the criteria are met both for a Manic Episode and a Major Depressive Episode.(4) Untreated Manic Episodes generally last three to six months and Depressive Episodes generally last six to 12 months without treatment.(5)

Bipolar Disorder affects 2.4 million people in Europe.(6)

European Media Webcast - Minds and Hearts: Bipolar I Disorder

You are invited to log onto a media webcast to view presentations from leading European psychiatrists. Presentations will focus on Bipolar I Disorder, the impact from a patient perspective and the impact of treatment options. www.bipolar-1-disorder.com

Notes to editors

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 commercialisation of ABILIFY(R). ABILIFY was discovered by Otsuka Pharmaceutical Co., Ltd. Founded in 1964, Otsuka Pharmaceutical Co., Ltd. is a healthcare company with the mission statement: “Otsuka - people creating new products for better health worldwide.” Otsuka researches, develops, manufactures and markets innovative, original products, focusing its core businesses on pharmaceutical products for the treatment of disease and consumer products for the maintenance of everyday health. The Otsuka Pharmaceutical Group comprises 106 companies and employs approximately 33,000 people in 18 countries and regions worldwide.

Bristol-Myers Squibb is a global biopharmaceutical whose mission is to extend and enhance human life.

About ABILIFY(R) (aripiprazole) in schizophrenia

ABILIFY(R) (aripiprazole) is manufactured in 5 mg, 10 mg, 15 mg and 30 mg tablets, 10 mg and 15 mg orodispersible tablets and 1 mg / ml oral solution.

ABILIFY is currently indicated for the treatment of schizophrenia; the current recommended dosing for ABILIFY in schizophrenia is a once-daily dose. The recommended starting dose is 10mg or 15mg, with a maintenance dose of 15mg.

About ABILIFY(R) (aripiprazole) in Bipolar I Disorder

Manic Episodes:

The recommended starting dose for ABILIFY is 15 mg administered on a once-a-day schedule without regard to meals as monotherapy or combination therapy (see SmPC section 5.1). Some patients may benefit from a higher dose. The maximum daily dose should not exceed 30 mg.

Recurrence prevention of Manic Episodes in Bipolar I Disorder:

For preventing recurrence of Manic Episodes in patients who have been receiving ABILIFY, continue therapy at the same dose. Adjustments of daily dosage, including dose reduction should be considered on the basis of clinical status.

The Marketing Authorisation Application for ABILIFY in Europe is supported by 8 Phase III clinical studies.

References

(1) Vieta E. et al. A 46 week evaluation of aripiprazole in combination with lithium/valproate in bipolar mania. Poster # 131. Presented at the annual congress of the World Psychiatric Association, 2 April 2009.

(2) Keck P.E, Sanchez R, Torbeyns A et al. Aripiprazole monotherapy in the treatment of acute bipolar I mania: a randomized, placebo- and lithium-controlled study (CN138-135). Poster presented at APA 160th Annual Meeting, San Diego, U.S., 19-27 May 2007.

(3) Dillenschneider A, Sanchez R, McQuade R.D, Torbeyns A. Aripiprazole monotherapy in acute bipolar I mania: a randomized, placebo- and haloperidol-controlled study (CN138-162). Poster presented at WEBP, Strasbourg, France, 13-15 December, 2007.

(4) American Psychiatric Association 2000. (DSM-IV-TR) Diagnostic and statistical manual of mental disorders, 4th edition, text revision. Washington, DC: American Psychiatric Press, Inc. p320-323, 328-330, 333, 350-351.

(5) Royal College of Psychiatrists. Bipolar Disorder (Manic Depression). www.rcpsych.ac.uk/mentalhealthinformation/mentalhealthproblems/bipolar manicdepression/bipolardisorder.aspx. Date accessed 11 January 2007.

(6) Wittchen H-U, Jacobi F. Size and burden of mental disorders in Europe - a critical review and appraisal of 27 studies. Eur Neuropsychopharmacol 2005; 15:357-376.

Source: Bristol-Myers Squibb and Otsuka Pharmaceutical Co. Ltd

CONTACT: Carmel Hogan, Bristol-Myers Squibb Company, Mobile: +33-6-74-10-76-58, carmel.hogan at bms.com; Alison Ross, Otsuka Pharmaceutical Europe Ltd, Mobile: +44(0)7768-337-128, aross at otsuka-europe.com