Otsuka and Lundbeck’s once-monthly Abilify Maintena® (aripiprazole) now approved in Europe for maintenance treatment of schizophrenia in adult patients stabilized with oral aripiprazole

• Preventing relapse is critical in the treatment of schizophrenia. Pivotal studies, that supported the EU submission, demonstrate that Abilify Maintena can reduce the risk of relapse relative to placebo and is non-inferior to oral aripiprazole in patients with schizophrenia^{1, 2}
• The approval of Abilify Maintena now provides patients with schizophrenia access to a once-monthly formulation with established efficacy together with a tolerability profile that is comparable to that of oral ABILIFY^® (aripiprazole)²
• At the end of the randomised, double-blind treatment phase in one of the pivotal trials, 93% of patients reported being extremely, very or somewhat satisfied with Abilify Maintena treatment³
• Abilify Maintena is the only dopamine D2 partial agonist in a once-monthly, injectable form to receive marketing authorisation in Europe for maintenance treatment of schizophrenia
• Abilify Maintena will be the first commercialised product in Europe from the global alliance between Otsuka and Lundbeck which is focused on developing Central Nervous System (CNS) therapies worldwide

Valby, Denmark and Tokyo, Japan, 21 November 2013 - H. Lundbeck A/S (Lundbeck) and Otsuka Pharmaceutical Co., Ltd. (Otsuka) today announced marketing authorisation approval from the European Commission for Abilify Maintena (aripiprazole), an intramuscular (IM) once-monthly injectable formulation for maintenance treatment of schizophrenia in adult patients stabilised with oral aripiprazole.

Abilify Maintena reduces the risk of relapse relative to placebo over the long-term and provides effective treatment of schizophrenia.^1,2 It has a tolerability profile similar to oral aripiprazole¹, and demonstrated statistically significant benefits on patients’ personal and social functioning as compared to placebo.^{1, 4}  

93% of patients treated with Abilify Maintena were extremely, very or somewhat satisfied with their treatment at the end of the double-blind treatment phase.⁴

“We strongly believe the schizophrenia community will welcome the availability of Abilify Maintena to help improve outcomes for patients living with schizophrenia. As a company, our focus is to develop treatments to help protect against relapse and preserve brain function,” said Ole Vahlgren, CEO & President, Otsuka Europe. “We must partner with health care professionals and caregivers to help patients get the best treatments that focus on reducing the risk of relapse.”

“Studies have shown that the early use of long-acting injectables can prevent a person with schizophrenia from experiencing a relapse⁵,” said Ole Chrintz, SVP International Markets & Europe, Lundbeck. “Efficacy is important, but a treatment for a chronic condition such as schizophrenia also needs to be well tolerated so patients will stay on it over the long-term. We believe Abilify Maintena meets this need.”^1,2,3

About the studies

The efficacy of Abilify Maintena was demonstrated in two double-blind, phase III, randomized trials. The safety profile for Abilify Maintena was demonstrated to be similar to that of oral ABILIFY. The most frequently observed adverse drug reactions (ADRs) reported in ≥5% of patients in two double-blind controlled clinical trials of Abilify Maintena were weight increases (9.0%), akathisia (7.9%), insomnia (5.8%), and injection site pain (5.1%).^1,2

About Abilify Maintena

Abilify Maintena is the only dopamine D2 partial agonist in once-monthly, injectable form to receive marketing authorisation for maintenance treatment in schizophrenia. Physicians now have an alternative treatment option, with a tolerability profile comparable to the well-established oral ABILIFY, to address the on-going need to reduce the risk of relapse in patients with schizophrenia.

The European label states that Abilify Maintena is a powder and solvent for prolonged-release suspension for intra-muscular (IM) injection. It is a once-monthly formulation of aripiprazole in a sterile lyophilised powder that is reconstituted with sterile water. Abilify Maintena is indicated for maintenance treatment of schizophrenia in adult patients stabilised with oral aripiprazole.

After the first injection, treatment with 10 mg to 20 mg oral aripiprazole should be continued for 14 consecutive days to maintain therapeutic aripiprazole concentrations during initiation of therapy.

About Schizophrenia and Disease Relapse

Schizophrenia is a disease characterised by a distortion in the process of thinking and of emotional responsiveness. It most commonly manifests as hallucinations, paranoid or bizarre delusions, or disorganised 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 lifelong treatment to mitigate symptoms.

Relapse of schizophrenia refers to an exacerbation or acute psychotic break that is characterised primarily by the emergence of positive symptoms such as hallucinations, delusions and disordered thinking⁶. 

Relapse can occur when a patient no longer responds to antipsychotic medication, does not take the medication as prescribed, or stops taking their medication altogether. There are many reasons patients stop taking their medication, including poor insight about their illness, side effects from current treatments, complicated medication regimen or lack of support from family⁷. Abilify Maintena is able to significantly reduce the risk of relapse in patients with schizophrenia¹.

It has been estimated that schizophrenia affects approximately one percent of the adult population in the U.S. and Europe, and approximately 24 million people worldwide^{8, 9}. In Europe there are approximately 4.4 million adults with schizophrenia¹⁰, prevalent equally in both genders^{11, 12}. 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 symptoms¹³.

Schizophrenia places a significant burden on society. It is regarded among the most financially costly illnesses and is according to the World Health Organization (WHO), the 8^th leading cause of DALYs (lost healthy years) worldwide among patients between the age of 15-44⁹. With 50% of patients not receiving appropriate care and 80% of patients relapsing within the first 5 years¹⁴, there is a significant unmet need to be addressed in schizophrenia.

Lundbeck contacts

Otsuka contacts:

Investors:                                                                                             Media:

EUROPE                                                                                               JAPAN/ASIA

Alison Ross                                                                                           Jeffrey Gilbert

Otsuka Pharmaceutical Europe Ltd.                                                                Otsuka Pharmaceutical Co., Ltd.

aross@otsuka-europe.com                                                               gilbert.jeffrey@otsuka.co.jp

+44 7768 337128                                                                                +81 3 6361 7379, +81 80 8728 6039

NORTH AMERICA

Rose Weldon

Otsuka America Pharmaceutical, Inc.

rose.weldon@otsuka-us.com

+1 609 524 6879, +1 215 801 7644 (cell)

Investors:

Takuma Kimura

Investor Relations Department

Otsuka Holdings Co., Ltd.

kimurata@otsuka.jp

+81 3 6361 74

About the Lundbeck and Otsuka Global Alliance

Lundbeck and Otsuka established a global alliance in November 2011 to bring to bear their considerable experience and resources in the CNS area to introduce next-generation treatments for conditions such as schizophrenia, depression, Alzheimer’s disease and alcohol dependency.

About Lundbeck

H. Lundbeck A/S (LUN.CO, LUN DC, HLUYY) is a global pharmaceutical company specialized in brain diseases. For more than 50 years, we have been at the forefront of research within neuroscience. Our development and distribution of pioneering treatments continues to make a difference to people living with brain diseases. Our key areas of focus are alcohol dependence, Alzheimer’s disease, depression/anxiety, epilepsy, Huntington’s disease, Parkinson’s disease, schizophrenia and stroke.

Our 5,800 employees in 57 countries are engaged in the entire value chain throughout research, development, production, marketing and sales, and are committed to improving the quality of life of people living with brain diseases. Our pipeline consists of several late-stage development programs and our products are available in more 100 countries. We have research centers in China, Denmark and the United States, and production facilities in China, Denmark, France, Italy and Mexico. Lundbeck generated revenue of approximately DKK 15 billion in 2012 (EUR 2 billion; USD 2.6 billion).

Lundbeck’s shares are listed on the stock exchange in Copenhagen under the symbol ”LUN”. Lundbeck has a sponsored Level 1 ADR program listed in the US (OTC) under the symbol ”HLUYY”. For additional information, we encourage you to visit our corporate site www.lundbeck.com.

About Otsuka Pharmaceutical Co., Ltd.

Otsuka Pharmaceutical Co., Ltd. is a global healthcare company with the corporate 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 nutraceutical products for the maintenance of everyday health.

In pharmaceuticals, Otsuka is a leading firm in the challenging area of mental health and also has research programs for several under-addressed diseases including tuberculosis, a significant global public health issue. These commitments illustrate more powerfully than words how Otsuka is a “big venture” company at heart, applying a youthful spirit of creativity in everything it does.

Otsuka is a wholly owned subsidiary of Otsuka Holdings Co., Ltd., the holding company for the Otsuka Group. The chairman Akihiko Otsuka is the third generation of Otsuka family members to lead the business, whose origins date from 1921. The Otsuka Group employs approximately 42,000 people globally and its products are available in more than 80 countries worldwide. Consolidated sales were approximately €10 billion or USD 13 billion for fiscal year 2012 (4/1/2012-3/31/2013). Otsuka Pharmaceutical welcomes you to visit its global website at https://www.otsuka.co.jp/en/

Safe Harbor/Forward-Looking Statements

The above information contains forward-looking statements that provide our expectations or forecasts of future events such as new product introductions, product approvals and financial performance.

Such forward-looking statements are subject to risks, uncertainties and inaccurate assumptions. This may cause actual results to differ materially from expectations and it may cause any or all of our forward-looking statements here or in other publications to be wrong. Factors that may affect future results include interest rate and currency exchange rate fluctuations, delay or failure of development projects, production problems, unexpected contract breaches or terminations, government-mandated or market-driven price decreases for Lundbeck's products, introduction of competing products, Lundbeck's ability to successfully market both new and existing products, exposure to product liability and other lawsuits, changes in reimbursement rules and governmental laws and related interpretation thereof, and unexpected growth in costs and expenses.

Certain assumptions made by Lundbeck are required by Danish Securities Law for full disclosure of material corporate information. Some assumptions, including assumptions relating to sales associated with product that is prescribed for unapproved uses, are made taking into account past performances of other similar drugs for similar disease states or past performance of the same drug in other regions where the product is currently marketed. It is important to note that although physicians may, as part of their freedom to practice medicine in the US, prescribe approved drugs for any use they deem appropriate, including unapproved uses, at Lundbeck, promotion of unapproved uses is strictly prohibited.

REFERENCES:

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):617-62
2. Fleischhacker WW, Sanchez R, Perry PP, et al. Aripiprazole once-monthly for the treatment of schizophrenia: a double-blind, randomized, non-inferiority study vs. oral aripiprazole. Annual Meeting of the American Psychiatric Association, 18–22 May, 2013 (poster).
3. Sanchez R, et al. Patient-reported Outcomes with Aripiprazole-Intramuscular-Depot for Long-term Maintenance Treatment in Schiziphrenia. NR6-42 2012 (poster)
4. Carson WH, Perry P, Sanchez R, et al. Effects of a Once-Monthly Formulation of Aripiprazole on Secondary Efficacy Outcomes in Maintenance Treatment of Schizophrenia. Institute on Psychiatric Services meeting, October 4–7, 2012 (Poster)
5. Long-acting injectable antipsychotics in the treatment of schizophrenia: their role in relapse prevention. Agid O, et al. Expert Opin. Pharmacother. (2010) 11(14):2301-2317
6. Ayuso-Gutierrez JL, del Rio Vega JM. Factors influencing relapse in the long-term course of schizophrenia. Schizophr Res. 1997; 28(2-3): 199-206
7. Baloush-Kleinman V, et al. Adherence to antipsychotic drug treatment in early-episode schizophrenia: a six-month naturalistic follow-up study. Schizophr Res. 2011;130(1-3):176-81.
8. National Institute of Mental Health (NIMH). Health Topics: Statistics. Available at http://www.nimh.nih.gov/statistics/1SCHIZ.shtml. Accessed October 22, 2013
9. World Health Organization (WHO). Schizophrenia Fact Sheet. 2010. Available at: http://www.who.int/mental_health/management/schizophrenia/en/. Accessed October 22, 2013.
10. World Health Organization (WHO) The global burden of disease:2004 update (2008)

1. National Institute of Mental Health (NIMH). The Numbers Count: Mental Disorders in America. 2010. Available at http://www.nimh.nih.gov/health/publications/the-numbers-count-mental-disorders-in-America/index.shtml#Schizophrenia. Accessed October22, 2013
2. Regier DA, et al. The de facto US mental and addictive disorders service system. Epidemiologic catchment area prospective 1-year prevalence rates of disorders and services. Arch Gen Psychiatry. 1993;50(2):85-94.
3. American Psychiatric Association. Practice guideline for the treatment of patients with schizophrenia. Second edition. 2004. Available at http://psychiatryonline.org/content.aspx?bookid=28&sectionid=1665359. Accessed October 28, 2013
4. Robinson D, et al. Predictors of relapse following response from a first episode of schizophrenia or schizoaffective disorder. Arch Gen Psychiatry. 1999;56(3):241-247