September 28, 2012

Application for time-window extension of the thrombolytic agents GRTPA® andACTIVACIN® up to 4.5 hours after the onset of symptoms ofischemic cerebrovascular disease
Osaka and Tokyo, Japan, September 28, 2012---Mitsubishi Tanabe Pharma Corporation (Presidentand Representative Director, Chief Executive Officer: Michihiro Tsuchiya) and Kyowa Hakko Kirin
Co., Ltd. (Executive Director of the Board President & Chief Executive Officer: Nobuo Hanai) filed atwo-company joint application with the Ministry of Health, Labour and Welfare on September 27,
2012. The public knowledge-based application is for a time-window extension of the thrombolytic
agents that are marketed in Japan by the two companies with indication to improve functional disability
in the acute ischemic cerebrovascular disease. Specifically, the application is for an extension from 3
hours after the onset of symptoms to 4.5 hours for GRTPA® and ACTIVACIN® for injection.
For cerebral infarction, which is the principal ischemic cerebrovascular disease, GRTPA® andACTIVACIN® are already in use for the improvement of functional disability in the acute stagepatients. However their use is currently limited to the 3-hour time-window after the onset of symptoms.
In recent years, a research team in Europe announced and reported clinical benefits from the use of
these drugs within 4.5 hours after the onset of symptoms. Based on that data, the treatment guidelines
in Europe and the United States have been revised, and administration to patients within 4.5 hours of
the onset of symptoms is now recommended.
Therefore, the Ministry of Health, Labour and Welfare asked for public opinion regarding thedevelopment of unapproved and Off-label drugs of High Medical need. The Japan Stroke Society
requested the time-window extension of these drugs from 3 hours after the onset of symptoms to 4.5
hours. Subsequently, at an April 2011 meeting of the Study Group on Unapproved and Off-label DrugsofHigh Medical Need*1 held in April 2011, the time-window extension of these drugs, as requestedby the Japan Stroke Society, was determined to have a high medical necessity, and Mitsubishi Tanabe
Pharma and Kyowa Hakko Kirin were asked to conduct the development. The two companies
presented documentation and other materials that comprised the foundation for public knowledge, andin August 2012, a decision was made that it would be appropriate to file a publicknowledge-based
application*2 in accordance with the evaluation of the Study Group. As a result of this decision,
Mitsubishi Tanabe Pharma and Kyowa Hakko Kirin filed a partial change application for these drugs.
Mitsubishi Tanabe Pharma and Kyowa Hakko Kirin believe that by obtaining approval for thetime-window extension of these drugs, they will be able to contribute to improving the treatment andQOL for more patients.

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Note 1. The Study Group on Unapproved and Off-label Drugs of High Medical Need
The Study Group evaluates the medical necessity of pharmaceutical indications that are approved inEurope and the U.S. but not yet approved in Japan; confirms the applicability of apublic-knowledge-based application and confirms the suitability of additional tests that need to beimplemented for the application. In this way, the Study Group was established to help advance thedevelopment by pharmaceutical companies of unapproved drugs / drugs used off label.
Note 2. Public knowledge-based application
For pharmaceuticals whose efficacy and safety are widely recognized, such as through the publicknowledge of medical societies, this system enables applications (additional indications, etc.), to be
filed without the implementation of all or a portion of clinical trials.

For further information:
Mitsubishi Tanabe Pharma Corporation,
Corporate Communications Department
TEL: +81-6-6205-5211
Kyowa Hakko Kirin Co., Ltd.,
Corporate Communications Department
TEL: +81-3-3282-1903

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