Otsuka Pharmaceutical Co., Ltd.

May 22, 2013

Study Shows Effects of Treatment with ABILIFY MAINTENA™ (Aripiprazole) on Psychiatric Hospitalization Rates for Patients with Schizophrenia

• Preliminary study analysis assessed total psychiatric hospitalization rates for patients with schizophrenia previously taking oral antipsychotics who were converted to ABILIFY MAINTENA^*1
• Results suggested that total psychiatric hospitalization rates in the prospective study period for ABILIFY MAINTENA were significantly reduced compared to hospitalization rates in the retrospective period when patients received oral antipsychotics (p<0.0001)^*1
• Data presented at the American Psychiatric Association Annual Meeting, May 18-22, 2013, and were recently published online in the Journal of Medical Economics

(SAN FRANCISCO, MAY 21, 2013) – Otsuka Pharmaceutical Co., Ltd. (Otsuka) and H. Lundbeck A/S (Lundbeck) today announced results from a preliminary analysis that showed statistically significant reductions (p<0.0001) in total psychiatric hospitalization rates in patients diagnosed with schizophrenia who were converted to once-monthly ABILIFY MAINTENA™ (aripiprazole) – an extended-release injectable suspension formulation of aripiprazole – compared to previous treatment with daily standard-of-care (SOC) oral antipsychotics.1 Relapse, or an acute exacerbation of the disease, can result in hospitalization.^*2 It also has been reported that hospitalization may contribute to higher health care costs.^*3 These data were presented in a poster at the 166th American Psychiatric Association (APA) Annual Meeting in San Francisco on May 21.^*1
"While further data are needed to confirm these findings, these results are exciting," said study investigator John M. Kane, M.D., Chairman of Psychiatry, The Zucker Hillside Hospital, and Vice President, Behavioral Health Services, North Shore-LIJ Health System. "Due to the nature of schizophrenia, patients are at high risk for hospitalization, which can often result from a disease relapse.2 So the more we can improve the management of symptoms, the better for patients and society as a whole."^*2,4 This multicenter, open-label, North American study used a mirror-image design to assess total psychiatric hospitalization rates – defined as proportion of patients with ≥1 inpatient psychiatric hospitalizations. The study was divided into two treatment periods: the first was a retrospective, six-month period assessing total psychiatric hospitalization rates in stable adult patients with schizophrenia treated with oral SOC antipsychotics; the second treatment period included these same patients who were then converted to treatment with ABILIFY MAINTENA (aripiprazole) once-monthly 400 mg for six months in the following prospective phases:^*1

• Phase A (1-4 weeks): a conversion phase where patients cross-titrated from their current oral antipsychotic to oral aripiprazole;
• Phase B (24 weeks): an open-label treatment phase where patients received ABILIFY MAINTENA (400 mg with an option to decrease to 300 mg for tolerability). As part of the study design, patients also received concomitant oral aripiprazole for the first 14 days of Phase B and:
• Phase C: an ongoing extension phase.

A total of 183 patients entered the prospective Phase B of the study, with 121 completing ≥ three months treatment with ABILIFY MAINTENA in Phase B. Total psychiatric hospitalization rates for the retrospective three-month analysis period in which patients received oral antipsychotics were 28.1 percent (n=34/121) compared to hospitalization rates of 6.6 percent (n=8/121) during the last three months of the prospective analysis period with ABILIFY MAINTENA (p<0.0001). Total psychiatric hospitalization rates for the retrospective six-month analysis period in which patients received oral antipsychotics were 41.5 percent (n=76/183) compared to hospitalization rates of 14.2 percent (n=26/183) for all patients who entered Phase B of the six-month prospective analysis period with ABILIFY MAINTENA (p<0.0001). The most common treatment-emergent adverse events with >5 percent incidence observed during the prospective Phase B were psychotic disorder (7.7 percent), insomnia (7.2 percent), akathisia (7.2 percent) and schizophrenia, paranoid type (5.5 percent). The incidence of weight change was 2.2 percent gained weight and 2.2 percent lost weight.^*1

About Schizophrenia

Schizophrenia is a disease characterized by a distortion in the process of thinking and of emotional responsiveness. It most commonly manifests as hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and is accompanied by significant social or occupational dysfunction. Onset of symptoms typically occurs in young adulthood and the condition is chronic, often requiring life-long treatment to mitigate symptoms. It has been estimated that schizophrenia affects approximately 1% of the adult population in the U.S., and approximately 24 million people worldwide.^*5,6,7 In the U.S., there are approximately 2.4 million adults with schizophrenia, prevalent equally in both genders.^*7,8
It has been reported that the financial burden of schizophrenia in the United States is estimated to be greater than that of all cancers.^*9 Based on the latest data (2002), excess direct health care costs of schizophrenia in the U.S. were approximately $22.7 billion, and included expenditures for hospitalization, as well as for physician and other professional services and medications.^*3 Additional U.S. 2002 data sets suggest approximately two schizophrenia-related hospitalizations can be estimated per every 1,000 adults per year,^*10,11 with a mean cost of $18,300 per hospitalization.^*10,12 Other studies assessing health care utilization have suggested that the use of long-acting injectable medications to treat schizophrenia may help reduce psychiatric hospitalizations^*13,14 and associated costs.^*13

About ABILIFY MAINTENA™ (aripiprazole)

ABILIFY MAINTENA for extended-release injectable suspension, an IM depot formulation of aripiprazole, is a sterile lyophilized powder that, when reconstituted with sterile water for injection, forms an injectable suspension that can be administered monthly. ABILIFY MAINTENA is indicated for the treatment of schizophrenia.
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. ABILIFY MAINTENA is not approved for the treatment of patients with dementia-related psychosis.
After an initial injection of ABILIFY MAINTENA along with an overlapping 14-day dosing of oral antipsychotic treatment, subsequent injections of ABILIFY MAINTENA provide uninterrupted medication coverage for 30 days at a time. Depot formulations of antipsychotic agents provide patients with concentrations of active drug that remain at a therapeutic range for an extended period of time.^*15,16The U.S. Food and Drug Administration (FDA) approved ABILIFY MAINTENA for the treatment of adults with schizophrenia on February 28, 2013. The product became available for prescribing in the U.S. on March 18, 2013.

• *1：Kane J et al. Hospitalization Rates In Patients Treated Previously With Oral Antipsychotics Vs. Prospectively Treated With Aripiprazole Once-Monthly: A Mirror Study. Poster presented at the American Psychiatric Association Annual Meeting; 2013 May 18-22; San Francisco, CA.
• *2：Kazadi, NJB et al. Factors associated with relapse in schizophrenia. South African Journal of Psychiatry. 2008; 14(2): 52-62.
• *3：E.Q. Wu et al. The Economic Burden of Schizophrenia in the United States in 2002. Journal of Clinical Psychiatry. 2005; 66(9): 1122-1129.
• *4：Ascher-Svanum, Haya et al. A comparison of olanzapine and risperidone on the psychiatric hospitalization in naturalistic treatment of patients with schizophrenia. Annals of General Hospital Psychiatry. 2004; 11(3): 1-11.
• *5：National Institute of Mental Health (NIMH). Health Topics: Statistics. Available at http://www.nimh.nih.gov/statistics/1SCHIZ.shtml. Accessed May 14, 2013.
• *6：World Health Organization (WHO). Schizophrenia Fact Sheet. 2010. Available at http://www.who.int/mental_health/management/schizophrenia/en/. Accessed May 14, 2013.
• *7：National Institutes of Mental Health (NIMH). The Numbers Count: Mental Disorders in America. Available at http://www.nimh.nih.gov/health/publications/the-numbers-count-mental-disorders-in-america/index.shtml. Accessed May 14, 2013.
• *8：Regier, Darrel et al. The de Facto US Mental and Addictive Disorder Service System. Archives of General Psychiatry. 1993; 50: 85-94.
• *9：Thaker, Gunvant K, William T. Carpenter. Advances in Schizophrenia. Nature Medicine. 2001; 7: 667-671.
• *10：Fortney, J. C., S. Xu, and F. Dong. Community-Level Correlates of Hospitalizations for Persons with Schizophrenia. Psychiatric Services. 2009: 772-78.
• *11：Kozak LJ, Owings MF, Hall MJ: National Hospital Discharge Survey: 2002 Annual Summary with Detailed Diagnosis and Procedure Data. Atlanta, Ga, Centers for Disease Control and Prevention, National Center for Health Statistics, 2005.
• *12：Merrill CT, Elixhauser A: Hospitalization in the United States, 2002. H-CUP Fact Book No 6, AHRQ pub no 05-056. Rockville, Md, Agency for Healthcare Research and Quality, 2005.
• *13：Xiaomei Peng,Haya Ascher-Svanum, Douglas Faries, Robert R Conley, and Kory J Schuh. Decline in hospitalization risk and health care cost after initiation of depot antipsychotics in the treatment of schizophrenia. Journal of ClinicoEconomics and Outcomes Research. 2011; 3: 9–14.
• *14：Offord, S, Wong B, Mirski D, Baker RA, Lin J. Healthcare resource usage of schizophrenia patients initiating long-acting injectable antipsychotics vs oral. Journal of Medical Economics. 2013;16(2):231-9
• *15：Prescribing Information. ABILIFY MAINTENA™ (aripiprazole) for extended-release injectable suspension, for intramuscular use. February 2013.
• *16：Kane JM, Sanchez R, Perry PP, et al. Aripiprazole intramuscular depot as maintenance treatment in patients with schizophrenia: a 52-week, multicenter, randomized, double- blind, placebo-controlled study. Journal of Clinical Psychiatry. 2012; 73(5): 617-624.