Otsuka Pharmaceutical Co., Ltd.

March 1, 2013

FDA Approves Once-Monthly ABILIFY MAINTENA™ (Aripiprazole) For Extended-Release Injectable Suspension for the Treatment of Schizophrenia

  • Approval provides patients with schizophrenia the ability to access the efficacy and safety profile of oral aripiprazole in a once-monthly formulation.
  • Relapse prevention is an important consideration in the treatment of patients with schizophrenia; ABILIFY MAINTENA met the Phase 3 clinical trial primary endpoint of significantly delaying time to relapse.
  • ABILIFY MAINTENA will be the first commercialized product from the global alliance between Otsuka and Lundbeck focused on developing Central Nervous System (CNS) therapies worldwide.

(Tokyo, Japan and Copenhagen, Denmark, March 1 2013) - Otsuka Pharmaceutical Co., Ltd. (Otsuka) and H. Lundbeck A/S (Lundbeck) announced the U.S. Food and Drug Administration (FDA) has approved ABILIFY MAINTENA™ (aripiprazole) for extended-release injectable suspension, an intramuscular (IM) depot formulation indicated for the treatment of schizophrenia.

ABILIFY MAINTENA is the first dopamine D2 partial agonist approved as a once- monthly injection. It contributes a new treatment option to address the ongoing need for relapse prevention in patients with schizophrenia, a chronic, debilitating disease.

Efficacy was demonstrated in a 52-week, placebo-controlled, double-blind, randomized-withdrawal, Phase 3 maintenance trial of ABILIFY MAINTENA in patients with schizophrenia. The time to relapse was the primary endpoint. In the trial, ABILIFY MAINTENA (n=269 adult patients) significantly delayed time to relapse compared to placebo (n=134 adult patients; hazard ratio = 5.03, 95% CI = 3.15-8.02, p<0.0001)*1. In a key secondary endpoint, the percentage of subjects experiencing relapse (i.e., meeting clinical trial criteria for exacerbation of psychotic symptoms/relapse) was also significantly lower with ABILIFY MAINTENA compared to placebo at the end of the study (10% vs. 40%, respectively; p<0.0001). Additional support for efficacy was derived from oral aripiprazole trials.

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. ABILIFY MAINTENA is contraindicated in patients with a known hypersensitivity reaction to aripiprazole. Reactions have ranged from pruritus/urticaria to anaphylaxis (see Important Safety Information below).

ABILIFY MAINTENA will be the first commercialized product from the long-term global alliance between Otsuka and Lundbeck to develop CNS medicines worldwide. The companies expect the product will start becoming available in the U.S. beginning March 18.

"Protection from relapse of schizophrenia is important for patients, their families and the communities in which they live," 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. "As a strong believer in long-acting therapies for schizophrenia, I think it is important for physicians to have a new and effective once-monthly treatment option that can help reduce the risk of relapse and manage symptoms in patients."

Results from the clinical trial of ABILIFY MAINTENA were published in the Journal of Clinical Psychiatry and first presented in four poster presentations at the 2012 American Psychiatric Association Annual Meeting in May 2012.

The trial included adult patients who met DSM-IV-TR criteria for schizophrenia and who were being treated with at least one antipsychotic medication. Patients had at least a 3-year history of illness and a history of relapse or symptom exacerbation when not receiving antipsychotic treatment. Patients in the study received injections of ABILIFY MAINTENA or placebo once every four weeks; the first injection was accompanied by two weeks of concomitant administration of oral aripiprazole. The trial included a pre-planned interim analysis which demonstrated a significantly longer time to relapse (p<0.001) in patients randomized to the ABILIFY MAINTENA group compared to placebo-treated patients. The trial was subsequently terminated early by an independent data monitoring committee because maintenance of efficacy was demonstrated. The final analysis demonstrated a statistically significantly longer time to relapse in patients randomized to the ABILIFY MAINTENA group than compared to placebo- treated patients (log-rank test p< 0.0001).

ABILIFY MAINTENA 300-400 mg has been evaluated for safety in 1,287 adult patients in clinical trials in schizophrenia, with approximately 1,281 patient-years of exposure to ABILIFY MAINTENA. A total of 832 patients were treated with ABILIFY MAINTENA for at least 180 days (at least seven consecutive injections) and 630 patients treated with ABILIFY MAINTENA had at least one year of exposure (at least 13 consecutive injections). The safety profile of ABILIFY MAINTENA is expected to be similar to that of oral aripiprazole. In patients who tolerated and responded to treatment with oral aripiprazole and single-blind ABILIFY MAINTENA and were then randomized to receive ABILIFY MAINTENA or placebo injections under double-blind conditions, the incidence of adverse reactions was similar between the two treatment groups. The only commonly observed adverse reaction associated with the use of oral aripiprazole in patients with schizophrenia (incidence of 5% or greater and aripiprazole incidence at least twice that for placebo) was akathisia (aripiprazole 8%; placebo 4%).

"Our efforts to bring ABILIFY MAINTENA to market demonstrate our long-term commitment to discover, develop and champion treatments for the most challenging psychiatric diseases," said Taro Iwamoto, President and Representative Director, Otsuka Pharmaceutical Co., Ltd. "With this important approval, more patients with schizophrenia will have access to the efficacy and safety profile of ABILIFY in a once-monthly formulation. We are excited to bring ABILIFY MAINTENA to market as part of our historic alliance with Lundbeck. Both companies are deeply committed to supporting the comprehensive needs of the mental health community, including patients, healthcare providers, caregivers and advocates."

Commenting on the first regulatory approval from the long-term alliance established between Otsuka and Lundbeck, Ulf Wiinberg, Chief Executive Officer, Lundbeck said, "ABILIFY MAINTENA represents an important treatment option for patients and their physicians and caregivers seeking an alternative long-term maintenance treatment for schizophrenia, and we are pleased to join Otsuka in launching the first product as part of our extensive global alliance. The launch of ABILIFY MAINTENA also represents Lundbeck's first entry into the U.S. psychiatry market, expanding our central nervous system focus strategically in the U.S."

On November 11, 2011 Otsuka Pharmaceutical Co., Ltd. and H. Lundbeck A/S announced the formation of an alliance to collaborate on the development and commercialization of up to five early- and late-stage compounds in development. The two companies will co- commercialize ABILIFY MAINTENA in the U.S. and will collaborate on the development and commercialization of aripiprazole IM depot formulation in other markets worldwide.

About Schizophrenia and Disease Relapse

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 Europe, and approximately 24 million people worldwide.*2,3 In the U.S., there are approximately 2.4 million adults with schizophrenia, prevalent equally in both genders.*4,5 While there is no cure for the disease, symptoms and risk of relapse can be managed in most patients with appropriate antipsychotic treatment. However, when the disease is not managed, patients are at increased risk of disease relapse, which can cause the re-emergence or worsening of psychotic symptoms.*6

Relapse of schizophrenia can occur when a patient no longer responds to antipsychotic medication or when patients stop taking their medication. There are many reasons patients stop taking their medication and they include: poor insight about their illness, side effects from their current treatment, complicated medication regimens or lack of support from their family.

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.

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.*7,8

  • *1:Kane, JM et al. "Aripiprazole Intramuscular Depot as Maintenance Treatment in Patients With Schizophrenia: A 52-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study." J Clin Psychiatry 2012;73(5):617-624.
  • *2:National Institute of Mental Health (NIMH). Health Topics: Statistics. Available at Accessed July 19, 2012.
  • *3:World Health Organization (WHO). Schizophrenia Fact Sheet. 2010. Available at Accessed July 16. 2012.
  • *4:Regier, Darrel et al. The de Facto US Mental and Addictive Disorder Service System. Arch Gen Psychiatry. 1993; 50: 85-94.
  • *5:National Institutes of Mental Health (NIMH). The Numbers Count: Mental Disorders in America. Available at Accessed December 5, 2012.
  • *6:Almond, S et al. Relapse in schizophrenia: costs, clinical outcomes and quality of life. British Journal of Psychiatry, 2004; 184: 346-351.
  • *7:Patel MX, David AS. "Why aren't depot antipsychotics prescribed more often and what can be done about it?" Adv Psychiatr Treat, 2005; 11: 203-213.
  • *8:Kane, JM et al. "Guidelines for depot antipsychotic treatment in schizophrenia." Eur Neuropsychopharmacol, 1998; 8(1): 55-66.