Eisai Submits Marketing Authorisation Application for Approval of Eribulin Mesylate in Europe, Based on Significant Overall Survival in Late Stage Breast Cancer

Eisai Europe Ltd. (TOKYO:4523) today announced that it has submitted a marketing authorization application to the European Medicines Agency (EMA) for approval of eribulin mesylate, also known as ‘E7389’, for the treatment of locally advanced or metastatic breast cancer in Europe. Eribulin mesylate, a non-taxane microtubule dynamics inhibitor, is an investigational chemical compound discovered and developed by Eisai. Regulatory applications for eribulin mesylate have also been submitted in the United States and Japan.

The submission is based primarily on data from a pivotal, global Phase III study known as "EMBRACE” (Eisai Metastatic Breast Cancer Study Assessing Physician’s Choice Versus E7389), which was an open-label, randomized, parallel two-arm, multi-center study with 762 women with locally recurrent or metastatic breast cancer previously treated with at least two chemotherapy regimens, including an anthracycline and a taxane.^{1, 2} Study results showed that it met its primary endpoint of demonstrating a statistically significant improvement in overall survival in eribulin mesylate treated patients compared with treatment of physician’s choice.ⁱⁱ

The patients were treated either with eribulin (administered intravenously over two to five minutes on days 1 and 8 every 21 days) or with treatment of physician's choice. Treatment of physician's choice was defined as any single agent chemotherapy, hormonal treatment or biological therapy approved for the treatment of cancer; or palliative treatment or radiotherapy administered according to local practice.

EMBRACE is the first global Phase III study to compare a new agent, eribulin mesylate, to real-world choices in heavily pre-treated patients with metastatic breast cancer. The Physician’s Choice (TPC) arm of the study was included following recognition of the heterogeneous nature of the patient population, as well as the need for clinicians to tailor treatment regimes for individual patients.

Eribulin mesylate has a distinct mechanism of action that suppresses microtubule dynamics without affecting microtubule shortening parameters.³ It is delivered as an IV infusion with an administration time of between two and five minutes on days one and eight of a 21-day cycle. The infusion time for eribulin mesylate is relatively short when compared to taxanes, such as docetaxel which has an infusion time of one hour (every three weeks).⁴ In addition, treatment with eribulin mesylate did not require any pre-medication.ⁱ

The most frequent adverse events (AEs) reported by patients treated with eribulin mesylate were asthenia (fatigue), neutropenia (low white blood cell count), alopecia (hair loss), nausea and peripheral neuropathy (numbness, tingling in different parts of the body).ⁱⁱ Patients with pre-existing neuropathy were enrolled into the trial.ⁱ

About Eribulin Mesylate
Eribulin mesylate (E7389) is an investigational agent being evaluated as a potential treatment for locally advanced or metastatic breast cancer. A non-taxane, microtubule dynamics inhibitor, it belongs to a class of antineoplastic agents, the halichondrins, which are natural products isolated from the marine sponge Halichondria okadai.ⁱⁱⁱ

About Advanced or Metastatic Breast Cancer
Advanced or metastatic breast cancer occurs when a malignant tumor in the breast spreads from its original site to other parts of the body.⁵ Approximately 30 percent of women initially diagnosed with earlier stages eventually develop recurrent or metastatic disease⁶, whilst one in twenty women are initially diagnosed with late stage breast cancer.⁷ In addition, only one in five women with metastatic breast cancer survive longer than five years.^vii

About Eisai
Eisai is one of the worlds leading R&D-based pharmaceutical companies that has defined its corporate mission as "giving first thought to patients and their families and to increasing the benefits health care provides,” which we call human health care (hhc).

Eisai concentrates its R&D activities in three key areas

Integrative Neuroscience, including: Alzheimer’s disease, multiple sclerosis, neuropathic pain, epilepsy, depression

Integrative Oncology including: anticancer therapies; tumor regression, tumor suppression, antibodies, etc and supportive cancer therapies; pain relief, nausea

Vascular/Immunological reaction including: acute coronary syndrome, atherothrombotic disease, severe sepsis, rheumatoid arthritis, psoriasis, Crohn’s disease

With operations in the U.S., Asia, Europe and its domestic home market of Japan, we employ more than 11,000 people worldwide.

In Europe, Eisai undertakes sales and marketing operations in over 20 markets, including the United Kingdom, France, Germany, Italy, Spain, Switzerland, Sweden, Ireland, Austria, Denmark, Finland, Norway, Portugal, Iceland, Czech Republic, Hungary, and Slovakia.

For further information please visit our web site www.eisai.co.jp

# # #

References
¹ Clinical Study Protocol. The EMBRACE Trial: Eisai Metastatic Breast Cancer Study Assessing Physician's Choice Versus E7389. Final Incorporating Amendment 1. August 8, 2006.
² Data on file received from US, Eisai Europe Ltd.
³ Smith JA, Wilson L, Azarenko O, et al. Eribulin binds at microtubule ends to a single site on tubulin to suppress dynamic instability. Biochemistry. 2010; 49 (6); 1331-1337
⁴ Taxotere 20mg and 80mg concentrate and solvent for infusion. Summary of Product Characteristics. Available from: http://www.medicines.org.uk/emc/document.aspx?documentId=4594 [updated 24/12/2008, accessed 29/03/10]
⁵ Komen SG. Facts for Life: Metastatic Breast Cancer. Available at http://ww5.komen.org/uploadedFiles/Content_Binaries/806-03201a.pdf.
⁶ O’Shaughnessy J. Extending Survival with Chemotherapy in Metastatic Breast Cancer. The Oncologist, October 2005; 10: 20-29. Available at http://theoncologist.alphamedpress.org/cgi/reprint/10/suppl_3/20.
⁷ Gonzalez-Angulo AM et al. Overview of Resistance to Systemic Therapy in Patients with Breast Cancer. Breast Cancer Chemosensitivity (Advances in Experimental Medicine and Biology) 2007; 608: 1-16.