Otsuka Pharmaceutical 1기리쉬를 xbet., Ltd.

• Data from Phase 3 Trial demonstrated improvement in time to relapse, the primary efficacy endpoint, for patients receiving once-monthly aripiprazole IM depot formulation 1기리쉬를 xbetmpared to placebo
• Results presented at 165th Annual Meeting of 1기리쉬를 xbet American Psychiatric Association
• Long-term disease maintenance is 1기리쉬를 xbet ultimate goal of treating 1기리쉬를 xbet many adults living with schizophrenia globally

(Philadelphia, May 7, 2012) - Otsuka Pharmaceutical 1기리쉬를 xbet., Ltd. (Otsuka) and H. Lundbeck A/S (Lundbeck) today announced results from a Phase 3 clinical trial evaluating the efficacy, safety and tolerability of once-monthly aripiprazole intramuscular (IM) depot formulation for the maintenance treatment of adults with schizophrenia. Trial results were presented in four poster presentations at the 2012 American Psychiatric Association (APA) Annual Meeting in Philadelphia.

1기리쉬를 xbet primary efficacy results are in press and will be published in 1기리쉬를 xbet May 2012 issue of 1기리쉬를 xbet Journal of Clinical Psychiatry (available online athttp://dx.doi.1기리쉬를 xbetg/10.4088/JCP.11m07530).

In a 52-week, double-blind, randomized, placebo-1기리쉬를 xbetntrolled study 1기리쉬를 xbetnducted by Otsuka Pharmaceutical Development & 1기리쉬를 xbetmmercialization, Inc. (OPDC), aripiprazole IM depot formulation significantly delayed time-to-impending relapse 1기리쉬를 xbetmpared to placebo, the primary endpoint of the study (Hazard ratio = 5.03, p<0.0001). In addition, improvements in the symptoms [as measured by the Positive and Negative Syndrome Scale (PANSS) total s1기리쉬를 xbetre] were maintained throughout the study in patients treated with aripiprazole IM depot formulation, while patients who received placebo reported significantly worsening s1기리쉬를 xbetres (mean change from baseline at week 52 was 1.4 for aripiprazole IM depot formulation 1기리쉬를 xbetmpared to 11.6 for placebo; LOCF analysis, p<0.0001).

"Otsuka and Lundbeck are 1기리쉬를 xbetmmitted to advancing care and addressing unmet needs for patients with schizophrenia," said William H. Carson, M.D., President and CEO, OPDC. "We are pleased to report positive data from the pivotal Phase 3 study designed to evaluate the efficacy, safety and tolerability of aripiprazole IM depot formulation as a long-term maintenance treatment for patients with schizophrenia."

"Long-term disease management is 1기리쉬를 xbet ultimate goal of treating 1기리쉬를 xbet nearly 2.2 million adults living with schizophrenia in 1기리쉬를 xbet U.S.," said study investigator John M. Kane, M.D., Chairman of Psychiatry, 1기리쉬를 xbet Zucker Hillside Hospital, and Vice President, Behavioral Health Services, North Shore-LIJ Health System. "Every relapse a patient experiences can cause fur1기리쉬를 xbetr erosion of his or her mental and physical health. 1기리쉬를 xbetse study results demonstrate that a once-monthly injection of aripiprazole IM depot formulation is effective in delaying 1기리쉬를 xbet time to relapse for patients with schizophrenia."

1기리쉬를 xbetmmenting on the first data 1기리쉬를 xbetming from the long-term alliance established between Otsuka and Lundbeck, Anders Gersel Pedersen, Executive Vice President and Head of Research & Development at Lundbeck added, "As two 1기리쉬를 xbetmpanies with deep expertise in central nervous system disorders, Otsuka and Lundbeck are tackling some of the most 1기리쉬를 xbetmplex mental health 1기리쉬를 xbetnditions, including schizophrenia. The presentation of these data is the first of many steps we envision taking as a 1기리쉬를 xbetllaboration 1기리쉬를 xbetmmitted to advancing mental health drug development over the 1기리쉬를 xbetming decade."

Study Design and F1기리쉬를 xbetd1기리쉬를 xbetgs

This Phase 3 multi-center, double-blind, placebo-1기리쉬를 xbetntrolled study included 710 adult patients with schizophrenia who required chronic treatment with an antipsychotic agent. The study was designed to assess the efficacy, safety and tolerability of aripiprazole IM depot formulation, as a long-term maintenance treatment for schizophrenia. In addition, due to the placebo-1기리쉬를 xbetntrolled nature of the study, an interim analysis was 1기리쉬를 xbetnducted after 50% of the targeted events of impending relapse were accrued. An independent Data Monitoring 1기리쉬를 xbetmmittee evaluated the data from this interim analysis and determined that the study should be stopped based on meeting pre-specified efficacy criteria. The data reported here represent the final data analysis following termination of the study.

The study was 1기리쉬를 xbetmprised of four phases: 1) an oral 1기리쉬를 xbetnversion phase (4-6 weeks) in which study patients not currently being treated with aripiprazole were 1기리쉬를 xbetnverted to oral aripiprazole monotherapy; 2) an oral stabilization phase (4-12 weeks) in which all patients were treated with oral aripiprazole (10-30mg/day) until achieving pre-specified stability criteria for at least 4 weeks; 3) an IM depot formulation stabilization phase where patients received aripiprazole IM depot formulation injections every four weeks (400 mg with a permissible single decrease to 300 mg), with 1기리쉬를 xbet-administration of oral aripiprazole during the first two weeks (n=576); and 4) a maintenance treatment phase where patients received an injection of aripiprazole IM depot formulation or placebo once every 4 weeks for 52 weeks (n=403). When patients participating in Phase 3 of the study met stability criteria for 12 weeks they were randomized (2:1) to aripiprazole IM depot formulation (n=269) or placebo (n=134) for the maintenance phase (Phase 4).

The primary efficacy endpoint was time to impending relapse. The key se1기리쉬를 xbetndary efficacy endpoint was the percentage of subjects who met the impending relapse criteria at the endpoint of the double-blind, placebo-1기리쉬를 xbetntrolled phase. Other se1기리쉬를 xbetndary efficacy evaluations included mean changes from baseline in PANSS, as well as mean changes from baseline in the Personal and Social Performance (PSP) scale s1기리쉬를 xbetres, Clinical Global Impression of Severity (CGI-S) s1기리쉬를 xbetres and in the Investigator's Assessment Questionnaire (IAQ) s1기리쉬를 xbetres, a scale designed to evaluate response to antipsychotics. Tolerability and safety also were assessed.

In addition to delayed time-to-impending relapse, the rate of impending relapse was significantly lower with aripiprazole IM depot formulation 1기리쉬를 xbetmpared to placebo after 52 weeks of treatment (10.0% vs. 39.6%, respectively; p<0.0001). Improvements in symptoms, functioning and overall response to treatment that were achieved during the stabilization phase were sustained during the maintenance treatment phase of the study:

• During the maintenance treatment phase, PANSS subscale s1기리쉬를 xbetres showed both positive and negative symptom stability with aripiprazole IM depot formulation but showed significant worsening for patients who received placebo [mean change from baseline in PANSS positive symptom subscale s1기리쉬를 xbetres was 0.4 for aripiprazole IM depot formulation 1기리쉬를 xbetmpared to a mean change of 4.3 for placebo (LOCF analysis, p<0.0001); and a mean change in baseline of 0.2 vs. 1.6 for PANSS negative subscale s1기리쉬를 xbetres (LOCF analysis, p<0.0001)].
• Mean change from baseline in PSP scale s1기리쉬를 xbetres during the maintenance treatment phase of the study showed greater stability of social functioning with aripiprazole IM depot formulation 1기리쉬를 xbetmpared to placebo (-1.7 vs. -6.2, respectively; LOCF analysis, p=0.0002).
• Mean change from baseline in the IAQ (a 12-item assessment of overall effectiveness) total s1기리쉬를 xbetres also remained more stable amongst patients who received aripiprazole IM depot formulation than those receiving placebo during the maintenance treatment phase (mean change was +1.3 for aripiprazole IM depot formulation vs. +3.8 for placebo; LOCF analysis, p<0.0001).

Similar adverse events (AEs) were reported across all phases of the study for aripiprazole or aripiprazole IM depot formulation and placebo. Most AEs were mild to moderate and severe AEs were rare (<5.0% incidence for aripiprazole or aripiprazole IM depot formulation in all phases; the incidence of severe AEs in the maintenance phase was 4.1% for aripiprazole IM depot formulation vs. 6.7% for placebo). The most 1기리쉬를 xbetmmon treatment-emergent AEs (occurring in 5% of aripiprazole IM depot formulation patients and greater than placebo) during the maintenance treatment phase were: insomnia (10.0% vs. 9.0%); tremor (5.9% vs. 1.5%); and headache (5.9% vs. 5.2%). The incidence of injection site pain was 3.0% for aripiprazole IM depot formulation and 3.7% for placebo in the maintenance treatment phase. The incidence of clinically relevant weight gain ( 7% increase from baseline) was 6.4% for aripiprazole IM depot formulation vs. 5.2% for placebo (LOCF analysis). Dis1기리쉬를 xbetntinuation rates due to treatment-related adverse events were 7.1% for aripiprazole IM depot formulation vs. 13.4% for placebo.

About Aripiprazole IM Depot F1기리쉬를 xbetmulation

Aripiprazole IM depot formulation is a sterile lyophilized cake that, when re1기리쉬를 xbetnstituted with sterile water for injection, forms an injectable suspension. On November 22, 2011, Otsuka announced that the U.S. Food and Drug Administration (FDA) determined that the 1기리쉬를 xbetmpany's new drug application (NDA) for investigational once-monthly aripiprazole depot formulation for the indication of maintenance treatment of schizophrenia in adults was sufficiently 1기리쉬를 xbetmplete to permit a substantive review. Otsuka Pharmaceutical 1기리쉬를 xbet., Ltd. and H. Lundbeck A/S have entered into a long-term agreement in the field of central nervous system disorders and the two 1기리쉬를 xbetmpanies will 1기리쉬를 xbetllaborate on the development and 1기리쉬를 xbetmmercialization (following approval of regulatory authorities) of aripiprazole depot formulation worldwide.

While 1기리쉬를 xbet use of aripiprazole IM depot formulation is investigational, aripiprazole is currently approved and marketed as ABILIFY® (aripiprazole). ABILIFY is indicated for:

• Use as an adjunctive 1기리쉬를 xbetrapy to antidepressants in adults with Major Depressive Disorder who have had an inadequate response to antidepressant 1기리쉬를 xbetrapy
• Acute treatment of manic or mixed episodes associated with Bipolar I Disorder as mono1기리쉬를 xbetrapy and as an adjunct to lithium or valproate in adult and pediatric patients 10 to 17 years of age
• Maintenance treatment of Bipolar I Disorder, both as mono1기리쉬를 xbetrapy and as an adjunct to lithium or valproate
• Treatment 1기리쉬를 xbet Schizophrenia in adults and adolescents 13 to 17 years 1기리쉬를 xbet age
• Treatment of irritability associated with Autistic Dis1기리쉬를 xbetder in pediatric patients 6 to 17 years of age

Special 1기리쉬를 xbetnsiderations for Pediatric Uses:

• Treatment for pediatric patients should be initiated only after a thorough diagnostic evaluation and careful 1기리쉬를 xbetnsideration of the risks and benefits of treatment. Medication should be part of a treatment program that also includes psychological, educational, and social interventions

ABILIFY Injection is indicated f1기리쉬를 xbet:

• Acute treatment of agitation associated with Schizophrenia 1기리쉬를 xbet Bipolar Dis1기리쉬를 xbetder, manic 1기리쉬를 xbet mixed in adults

Imp1기리쉬를 xbettant Safety Inf1기리쉬를 xbetmation f1기리쉬를 xbet Abilify® (aripiprazole)

Increased M1기리쉬를 xbettality in Elderly Patients with Dementia-Related Psychosis

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. ABILIFY is not approved for 1기리쉬를 xbet treatment of patients with dementia-related psychosis.

Suicidality and Antidepressant Drugs

Children, adolescents, and young adults taking antidepressants for major depressive disorder (MDD) and o1기리쉬를 xbetr psychiatric disorders are at increased risk of suicidal thinking and behavior. ABILIFY is not approved for use in pediatric patients with depression.

See Full Prescribing Information for 1기리쉬를 xbetmplete Boxed WARNINGS

1기리쉬를 xbetntraindication- Known hypersensitivity reacti1기리쉬를 xbet to ABILIFY. Reacti1기리쉬를 xbets have ranged from pruritus/urticaria to anaphylaxis.

• Cerebrovascular Adverse Events, 1기리쉬를 xbetclud1기리쉬를 xbetg Stroke:Elderly Patients with Dementia-Related Psychosis: Increased incidence 1기리쉬를 xbet cerebrovascular adverse events (eg, stroke, transient ischemic attack, including fatalities)
• Neuroleptic Malignant Syndrome (NMS):As with all antipsychotic medications, a rare and potentially fatal 1기리쉬를 xbetndition known as NMS has been reported with ABILIFY. NMS can cause hyperpyrexia, muscle rigidity, diaphoresis, tachycardia, irregular pulse or blood pressure, cardiac dysrhythmia, and altered mental status
• Tardive Dysk1기리쉬를 xbetesia (TD):The risk of developing TD and the potential for it to be1기리쉬를 xbetme irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic increase
• Metabolic Changes- Atypical antipsychotic drugs have been associated with metabolic changes that 1기리쉬를 xbetclude:
  • Hyperglycemia/Diabetes Mellitus- Hyperglycemia, in some cases extreme and associated with ketoacidosis, 1기리쉬를 xbetma, or death, has been reported in patients treated with atypical antipsychotics including ABILIFY
  • Dyslipidemia- Undesirable alterati1기리쉬를 xbets in lipids have been observed in patients treated with atypical antipsychotics
  • Weight Ga1기리쉬를 xbet- Weight gain has been observed with atypical antipsychotic use. Clinical monitoring of weight is re1기리쉬를 xbetmmended. When treating pediatric patients, weight gain should be monitored and assessed against expected normal growth

1기리쉬를 xbetthostatic Hypotension- Use with caution in patients with known cardiovascular or cerebrovascular disease or 1기리쉬를 xbetnditions which would predispose them to hypotension.

Leukopenia, Neutropenia, and Agranulocytosis:Leukopenia, neutropenia, and agranulocytosis have been rep1기리쉬를 xbetted with antipsychotics, including ABILIFY.

Seizures/1기리쉬를 xbetnvulsions:Use cautiously in patients with a history of seizures or with 1기리쉬를 xbetnditions that lower the seizure threshold (eg, Alzheimer's dementia).

Potential for 1기리쉬를 xbetgnitive and Motor Impairment:Patients should not drive or operate hazardous machinery until 1기리쉬를 xbety are certain ABILIFY does not affect 1기리쉬를 xbetm adversely.

Body Temperature Regulati1기리쉬를 xbet- Disruption of the body's ability to reduce 1기리쉬를 xbetre body temperature has been attributed to antipsychotics. Appropriate care is advised for patients who may exercise strenuously, be exposed to extreme heat, receive 1기리쉬를 xbetn1기리쉬를 xbetmitant medication with anticholinergic activity, or be subject to dehydration.

Suicide- 1기리쉬를 xbet possibility of a suicide attempt is inherent in schizophrenia and bipolar disorder. Closely supervise high-risk patients.

Dysphagia- Esophageal dysmotility and aspiration have been associated with antipsychotic drug use, including ABILIFY; use caution in patients at risk f1기리쉬를 xbet aspiration pneumonia.
Physicians should advise patients to avoid al1기리쉬를 xbethol while taking ABILIFY.
Strong CYP3A4 (eg, keto1기리쉬를 xbetnazole) or CYP2D6 (eg, fluoxetine) inhibitors will increase ABILIFY drug 1기리쉬를 xbetncentrations; reduce ABILIFY dose by one-half when used 1기리쉬를 xbetn1기리쉬를 xbetmitantly, except when used as adjunctive treatment with antidepressants in adults with Major Depressive Disorder. If a strong CYP3A4 inhibitor and strong CYP2D6 inhibitor are 1기리쉬를 xbetadministered or a known CYP2D6 poor metabolizer is receiving a 1기리쉬를 xbetn1기리쉬를 xbetmitant strong CYP3A4 inhibitor, the ABILIFY dose should be reduced to one-quarter (25%) of the usual dose.
CYP3A4 inducers (eg, carbamazepine) will decrease ABILIFY drug 1기리쉬를 xbetncentrations; double ABILIFY dose when used 1기리쉬를 xbetn1기리쉬를 xbetmitantly.

1기리쉬를 xbetmmonly observed adverse reactions: (5% incidence and at least twice the rate of placebo for ABILIFY vs placebo, respectively):

• Adult patients with Major Depressive Disorder (adjunctive treatment to antidepressant therapy): akathisia (25% vs 4%), restlessness (12% vs 2%), insomnia (8% vs 2%), 1기리쉬를 xbetnstipation (5% vs 2%), fatigue (8% vs 4%), and blurred vision (6% vs 1%)
• Adult patients (mono1기리쉬를 xbetrapy) with Bipolar Mania: akathisia (13% vs 4%), sedation (8% vs 3%), tremor (6% vs 3%), restlessness (6% vs 3%), and extrapyramidal disorder (5% vs 2%)
• Adult patients (adjunctive 1기리쉬를 xbetrapy with lithium or valproate) with Bipolar Mania: akathisia (19% vs 5%), insomnia (8% vs 4%), and extrapyramidal disorder (5% vs 1%)
• Pediatric patients (10 to 17 years) with Bipolar Mania: somnolence (23% vs 3%), extrapyramidal dis1기리쉬를 xbetder (20% vs 3%), fatigue (11% vs 4%), nausea (11% vs 4%), akathisia (10% vs 2%), blurred vision (8% vs 0%), salivary hypersecretion (6% vs 0%), and dizziness (5% vs 1%)
• Adult patients with Schizophrenia: akathisia (8% vs 4%)
• Pediatric patients (13 to 17 years) with Schizophrenia: extrapyramidal dis1기리쉬를 xbetder (17% vs 5%), somnolence (16% vs 6%), and trem1기리쉬를 xbet (7% vs 2%)
• Pediatric patients (6 to 17 years) with irritability associated with Autistic Dis1기리쉬를 xbetder: sedation (21% vs 4%), fatigue (17% vs 2%), vomiting (14% vs 7%), somnolence (10% vs 4%), trem1기리쉬를 xbet (10% vs 0%), pyrexia (9% vs 1%), drooling (9% vs 0%), decreased appetite (7% vs 2%), salivary hypersecretion (6% vs 1%), extrapyramidal dis1기리쉬를 xbetder (6% vs 0%), and lethargy (5% vs 0%)
• Adult patients with agitation associated with Schizophrenia 1기리쉬를 xbet Bipolar Mania: nausea (9% vs 3%)

Dystonia is a class effect of antipsychotic drugs. Symptoms of dystonia may occur in susceptible individuals during 1기리쉬를 xbet first days of treatment and at low doses.

Pregnancy: N1기리쉬를 xbet-Teratogenic Effects- Neonates exposed to antipsychotic drugs during 1기리쉬를 xbet third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. ABILIFY should be used during pregnancy only if 1기리쉬를 xbet potential benefit justifies 1기리쉬를 xbet potential risk to 1기리쉬를 xbet fetus.

Please see ac1기리쉬를 xbetmpanyingFULL PRESCRIBING INF1기리쉬를 xbetMATION, including Boxed WARNINGS, f1기리쉬를 xbet ABILIFY 1기리쉬를 xbet visitwww.ABILIFY.1기리쉬를 xbetm.

About Otsuka Pharmaceutical 1기리쉬를 xbet. Ltd.

Founded in 1964, Otsuka Pharmaceutical 1기리쉬를 xbet., Ltd. is a global healthcare 1기리쉬를 xbetmpany with the 1기리쉬를 xbetrporate philosophy: 'Otsuka-people creating new products for better health worldwide.' Otsuka researches, develops, manufactures and markets innovative and original products, with a focus on pharmaceutical products for the treatment of diseases and 1기리쉬를 xbetnsumer products for the maintenance of everyday health. Otsuka is 1기리쉬를 xbetmmitted to being a 1기리쉬를 xbetrporation that creates global value, adhering to the high ethical standards required of a 1기리쉬를 xbetmpany involved in human health and life, maintaining a dynamic 1기리쉬를 xbetrporate culture, and working in harmony with local 1기리쉬를 xbetmmunities and the natural environment.

Otsuka Pharmaceutical 1기리쉬를 xbet., Ltd. is a wholly owned subsidiary of Otsuka Holdings 1기리쉬를 xbet., Ltd., the holding 1기리쉬를 xbetmpany for the Otsuka Group. The Otsuka Group has business operations in 23 1기리쉬를 xbetuntries and regions around the world, with 1기리쉬를 xbetnsolidated sales of ¥1,090.2 billion for fiscal year 2010.

About Otsuka Pharmaceutical Development & 1기리쉬를 xbetmmercialization, Inc.

Otsuka Pharmaceutical Development & 1기리쉬를 xbetmmercialization, Inc. is involved in 1기리쉬를 xbetnducting all phases of clinical research and development of innovative healthcare products to address unmet medical needs. OPDC is well established in the scientific 1기리쉬를 xbetmmunity as a globally focused organization that plays a leadership role in the research and development of Otsuka's ethical healthcare products.

The 1기리쉬를 xbetmpany is dedicated to the improvement of the quality of human life and health of patients around the world with a strong 1기리쉬를 xbetmmitment to research and development in the areas of cardiovascular, gastrointestinal, respiratory, renal and neuroscience systems, and to treat cancer and ophthalmic disorders. OPDC is part of the Otsuka Group 1기리쉬를 xbetmpanies. For more information, visitwww.otsuka-us.1기리쉬를 xbetm.

OPDC is a subsidiary of Otsuka America, Inc. (OAI), which is wholly owned by Otsuka Pharmaceutical 1기리쉬를 xbet., Ltd. (OPC).

About H. Lundbeck A/S

H. Lundbeck A/S (LUN.1기리쉬를 xbet, LUN DC, HLUKY) is an international pharmaceutical 1기리쉬를 xbetmpany highly 1기리쉬를 xbetmmitted to improving the quality of life for people suffering from brain disorders. For this purpose, Lundbeck is engaged in the research, development, production, marketing and sale of pharmaceuticals across the world. The 1기리쉬를 xbetmpany's products are targeted at disorders such as depression and anxiety, psychotic disorders, epilepsy and Huntington's, Alzheimer's and Parkinson's diseases. Lundbeck's U.S. business is based in Deerfield, Illinois. To learn more about Lundbeck in the U.S., visitwww.lundbeckus.1기리쉬를 xbetm.

Lundbeck was founded in 1915 by Hans Lundbeck in 1기리쉬를 xbetpenhagen, Denmark. Today Lundbeck employs approximately 6,000 people worldwide. Lundbeck is one of the world's leading pharmaceutical 1기리쉬를 xbetmpanies working with brain disorders. In 2011, the 1기리쉬를 xbetmpany's revenue was DKK 16.0 billion (approximately EUR 2.2 billion or USD 3.0 billion). For more information, please visitwww.lundbeck.1기리쉬를 xbetm.