Study Published in the Lancet Shows Eisai's Halaven(TM)(Eribulin) Significantly Improves Overall Survival Compared With Current Treatments in Heavily Pre-Treated Metastatic Breast Cancer

HATFIELD, England, March 3, 2011 /PRNewswire/ --

- Updated Phase III Data confirms Significant Survival Benefit Ahead of Impending European Launch

New data supporting the role of Eisai's Halaven(TM) (eribulin) as a potential new standard of care for women with heavily pretreated metastatic breast cancer (MBC) were published in The Lancet today. The EMBRACE trial (Eisai Metastatic Breast Cancer Study Assessing Treatment of Physician's Choice Versus Eribulin E7389) demonstrated that Halaven significantly improved overall survival (OS) compared with treatment of physician's choice (TPC) in women with MBC previously treated with at least an anthracycline and a taxane.[1] TPC is defined as any single-agent chemotherapy, hormonal treatment or biologic therapy approved for the treatment of cancer, or palliative treatment or radiotherapy administered according to local practice.[2]

"There is an urgent need for therapies with a proven survival benefit for women with metastatic breast cancer who have already received multiple treatments," commented Dr. Javier Cortes, lead author and investigator for the EMBRACE study and Specialist Physician at the Oncology Department of Vall d'Hebron University Hospital, Barcelona, Spain. "In the EMBRACE study we see a clear overall survival benefit for these patients when treated with Halaven. This is a remarkable step forward in this treatment setting where previously overall survival has been considered an endpoint difficult to attain."

EMBRACE met its primary endpoint, demonstrating a statistically significant increase in OS in the intention to treat (ITT) population for Halaven compared with TPC of 2.5 months (median 13.1 and 10.6 months respectively; p=0.041; hazard ratio [HR] 0.81). EMBRACE showed Halaven to have a predictable and manageable side effect profile with the most common adverse events in both arms being fatigue (53.7% with Halaven, 39.7% with TPC) and neutropaenia, or abnormally low levels of neutrophil white blood cells (51.7% with Halaven, 29.6% with TPC).[1]

"The publication of EMBRACE in The Lancet further reinforces the importance of Halaven as a potential new treatment for patients with metastatic breast cancer," said Uday Bose, Head of Institutional Care, Eisai Europe, Ltd. "These data open the door for a new treatment strategy in Europe, and one that will benefit patients who previously had very limited options. We are looking forward to the potential forthcoming authorisation of Halaven in Europe."

Halaven, a new, first-in-class type of chemotherapy, is a non-taxane, microtubule dynamics inhibitor belonging to the halichondrin class of antineoplastic agents. It is a structurally simplified synthetic analogue of halichondrin B, a natural product isolated from the marine sponge Halichondria okadai.[3][4] Eisai recently received positive opinion from The Committee for Medicinal Products for Human Use (CHMP) for the use of Halaven as a monotherapy in the treatment of patients with locally advanced or metastatic breast cancer who have progressed after at least two chemotherapeutic regimens for advanced disease. Prior therapy should have included an anthracycline and a taxane unless patients were not suitable for these treatments. Halaven has already received FDA approval in the United States.

About EMBRACE

EMBRACE was an open-label, randomised, multi-centre study of 762 women with MBC who were previously treated with at least two and a maximum of five prior chemotherapies (greater than or equal to 2 for advanced disease), including an anthracycline and a taxane. Patients must have been refractory to the most recent chemotherapy, documented by progression on or within six months of therapy. The study was designed to compare OS in patients treated with Halaven versus a TPC arm, reflecting a real-world clinical setting where a variety of agents are used to treat patients. The primary endpoint was OS. Secondary endpoints were objective response rate, progression-free survival, safety and duration of response.[1]

NOTES TO EDITORS

About Halaven(TM)

Halaven is a non-taxane, microtubule dynamics inhibitor, belonging to a class of antineoplastic agents, the halichondrins, which are natural products isolated from the marine sponge Halichondria okadai.[3,4] Halaven targets microtubules, the major cytoskeletal component of cells which play a pivotal role in cell replication. Alteration of microtubule dynamics can cause a cell to stop dividing and self destruct.

Geographical exploratory subgroup analyses demonstrated that Halaven significantly improved OS in region 1 (North America, Western Europe & Australia) compared with TPC (median 13.1 and 10.1 months, respectively; p=0.009; HR 0.72).[1]

About Metastatic Breast Cancer

Worldwide, more than one million women a year are diagnosed with breast cancer, including 421,000 women in Europe.[5],[6] Approximately 30 percent of women initially diagnosed with earlier stages of breast cancer eventually develop recurrent or metastatic disease,[7] and while around 9 out of 10 of women diagnosed with early stage breast cancer survive beyond five years, this drops to around 1 in 10 among women first diagnosed with MBC.[8] Most MBC patients have a limited survival time of approximately 18-24 months.[9]

Eisai in Oncology

Eisai is dedicated to discovering, developing and producing innovative oncology therapies that can make a difference and impact the lives of patients and their families. This passion for people is part of Eisai's human health care (hhc) mission, which strives for better understanding of the needs of patients and their families to increase the benefits health care provides. Our commitment to meaningful progress in oncology research, built on scientific expertise, is supported by a global capability to conduct discovery and preclinical research, and develop small molecules, therapeutic vaccines, biologic and supportive care agents for cancer across multiple indications.

Eisai Europe, Ltd.

    
    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; vaccines, tumor
      regression, tumor suppression, antibodies and supportive cancer
      therapies; pain relief, nausea

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

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, Slovakia and the Netherlands.

Eisai Co., Ltd.

Eisai Co., Ltd. is a research-based human health care (hhc) company that discovers, develops and markets products throughout the world. Through a global network of research facilities, manufacturing sites and marketing subsidiaries, Eisai actively participates in all aspects of the worldwide health care system. Eisai employs approximately 11,000 employees worldwide.

For further information, please visit http://www.eisai.co.jp.

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[1] Cortes J, O'Shaughnessy J, Loesch D, et al. A Phase III open-lable randomized study (EMBRACE) or eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer. The Lancet. 2011; 377: 1-10.

[2] Twelves C et al. Updated Survival Analysis of a Phase III Study (EMBRACE) of Eribulin Mesylate Versus Treatment of Physician's Choice in Subjects with Locally Recurrent or Metastatic Breast Cancer Previously Treated with an Anthracycline and a Taxane. San Antonio Breast Cancer Symposium (SABCS) 2010; Poster P6-14-18.

[3] Kuznetsov G, Towle MJ, Cheng H, et al: Induction of morphological and biochemical apoptosis following prolonged mitotic blockage by halichondrin B macrocyclic ketone analog E7389. Cancer Res 2004; 64: 5760-5766

[4] Towle MJ, et al. In Vitro and In Vivo Anticancer Activities of Synthetic Macrocyclic Ketone Analogues of Halichondrin B. Cancer Res 2001; 61: 1013-1021

[5] Coughlin, S. Breast cancer as a global health concern. Cancer Epidemiology, October 2009; 33: 315-18.

[6] Ferlay J, Parkin DM, Steliarova-Foucher E. Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer.2010: 46(4):765-781

[7] O'Shaughnessy J. Extending survival with chemotherapy in metastatic breast cancer. Oncologist. 2005;10 Suppl 3:20-29

[8] Cancer Research UK, Breast Cancer Statistics - Key Facts [updated April 2010]. Available from: http://info.cancerresearchuk.org/cancerstats/types/breast/index.htm?script=true (accessed (04/08/10)

[9] Fernandez Y, Cueva J, Palomo AG, et al. Novel therapeutic approaches to the treatment of metastatic breast cancer. Cancer Treat Rev.2010:36(1):33-42

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