Eisai's Eribulin Mesylate Maintains Overall Survival Benefit in Patients With Metastatic Breast Cancer, Irrespective of Tumour Hormone Receptor Status

By Eisai Europe Ltd., PRNE
Saturday, October 9, 2010

Results From the EMBRACE Study Reinforce Efficacy of Eribulin Across Several Patient Sub-Groups

MILAN, October 10, 2010 - Further results from the Phase III EMBRACE study presented today at the
European Society of Medical Oncology (ESMO) congress showed that Eisai's
eribulin mesylate maintained an overall survival (OS) benefit compared with
Treatment of Physician's Choice (TPC) in metastatic breast cancer (MBC)
patients, irrespective of their tumour hormone receptor status, extent of
disease or prior therapy.[1]

Additional analyses of the EMBRACE study (Eisai Metastatic Breast Cancer
Study Assessing Physician's Choice Versus Eribulin E7389) investigated the
primary endpoint of OS benefit of eribulin versus TPC within several
pre-specified sub-groups, including: hormone receptor expression status,
number of organs involved, sites of disease and prior treatment with
capecitabine. The results demonstrated that OS benefit with eribulin was
maintained in a number of clinically relevant subgroups, compared with TPC1 -
these results were consistent with those seen in the original Phase III
EMBRACE trial data presented at the American Society of Clinical Oncology
(ASCO) meeting earlier this year.[2]

"There continues to be significant unmet need for novel therapies that
improve overall survival in advanced metastatic breast cancer, which are also
well-tolerated and easily administered" said Dr. Chris Twelves, lead
investigator for the EMBRACE study and Professor of Clinical Cancer
Pharmacology and Oncology from the University of Leeds and St. James's
University Hospital, Leeds, United Kingdom. He went on to say that, "These
findings show that eribulin is an additional, effective treatment option for
a wide group of heavily pre-treated patients, and takes us closer to
establishing a standard of care in this group of patients with metastatic
breast cancer".

Worldwide, more than one million women a year are diagnosed with breast
cancer, including 421,000 women in Europe.[3],[4] Approximately 30 percent of
women initially diagnosed with earlier stages of breast cancer eventually
develop recurrent or metastatic disease.[5]

According to Dr. Javier Cortes, Professor of Medicine and Breast Cancer
Program Head at the Vall d'Hebron University Hospital, Barcelona, Spain:
"Eribulin is the first monotherapy to provide statistically significant
overall survival improvements in MBC patients previously treated with an
anthracycline and a taxane. This is an important step forward in terms of
treatment options in MBC, as there is currently no gold standard of care for
these patients."

Regulatory applications have been made for eribulin in the U.S., Europe,
Switzerland, Japan and Singapore - both Japan and the U.S. Food and Drug
Administration (FDA) have granted it priority review status.

The most frequently reported adverse events (AEs) among patients treated
with eribulin were asthenia, or fatigue, neutropenia, or low white blood cell
counts and peripheral neuropathy, or numbness and tingling in the feet and

About The EMBRACE Study

EMBRACE was an open-label, randomized, multi-center study of 762 patients
with locally recurrent or metastatic breast cancer who were previously
treated with at least two and a maximum of five prior chemotherapies (equal
to or more than 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 overall survival in patients treated with eribulin
versus a TPC arm, reflecting a real-world clinical setting where a variety of
agents are used to treat patients with advanced breast cancer.[2]

About the EMBRACE Sub-Analyses

Pre-specified exploratory subgroups in the EMBRACE study design are
hormone receptor expression status (estrogen receptor [ER], progesterone
receptor [PR], human epidermal growth factor receptor 2 [HER2], and triple
[ER/PR/HER2] negative), number of organs involved and prior capecitabine.

The subgroup analyses demonstrated that in a number of clinically
relevant subgroups, OS benefit with eribulin compared with TPC was
maintained. For patients with ER/PR positive (n=528) and ER/PR negative
(n=187) disease, hazard ratio (HR) of 0.83 (95% CI 0.64, 1.06) and HR of 0.66
(0.45, 0.99), respectively, were seen. In HER2 positive (n=123) and HER2
negative (n=565) subgroups, the HRs were 0.76 (0.47, 1.24) and 0.81 (0.64,
1.02), respectively. In the triple receptor (ER/PR/HER2) negative subgroup
(n=144), HR 0.71 (0.46, 1.10) was observed.

For equal to or less than 2 and 2 organs involved, visceral and
non-visceral disease, and no prior or prior capecitabine, the HRs were
0.80 (0.62, 1.04) and 0.81 (0.57, 1.17), 0.77 (0.62, 0.96) and 1.04
(0.56, 1.91), and 0.94 (0.62, 1.44) and 0.77 (0.61, 0.97), respectively.

In heavily pre-treated MBC patients, eribulin has demonstrated a
statistically significant improvement in OS by a median of 2.5 months
compared with TPC. These exploratory subgroup analyses also favoured eribulin
compared with TPC, with data that were consistent with the OS results.


About Eribulin

Eribulin 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.[6],[7] Eribulin has a
novel method of action that is distinct from those of other tubulin-targeted
agents currently in use. It 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.

While tubulin-targeting drugs such as taxanes and vinca alkaloids inhibit
cell division by stabilising microtubules and decreasing their mass, or
destabilising microtubules and increasing their mass respectively, the
effects of eribulin on dynamic instability are novel. Eribulin inhibits the
replication of cancer cells by suppressing the growth of microtubules,
without impacting other dynamic instability parameters (i.e. microtubule
shortening).[8] This novel mode of action may have the potential to reduce
treatment toxicity to normal tissue, while retaining effective anti-tumour

About Metastatic Breast Cancer

Worldwide, more than one million women a year are diagnosed with breast
cancer, including 421,000 women in Europe.[3,4] Approximately 30 percent of
women initially diagnosed with earlier stages of breast cancer eventually
develop recurrent or metastatic disease,[5] 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.[10] Most
MBC patients have a limited survival time of approximately 18-24 months.[11]

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

    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 and Slovakia.

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 www.eisai.co.jp.


[1] Twelves C, Akerele C, Wanders J, Cortes J. Eribulin Mesylate (E7389)
vs. Treatment of Physician's Choice (TPC) in Patients with Metastatic Breast
Cancer: Subgroup Analyses from the EMBRACE Study.

Abstract 2750, presented at the ESMO Congress, 8th September 2010, Milan,

[2] Twelves C et al. A Phase III Study (EMBRACE) of Eribulin Mesylate vs
Treatment of Physician's Choice in Patients with Locally Recurrent or
Metastatic Breast Cancer Previously Treated with an Anthracycline and a
Taxane. Abstract 1084, American Society of Clinical Oncology (ASCO) congress,
Chicago, 2010.

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

[4] 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

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

[6] 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

[7] 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

[8] Smith JA, Wilson L, Azarenko O, et al. Eribulin binds at microtubule
ends to a single site on tubulin to suppress dynamic instability.

[9] Zhou J, Giannakakou. Targeting Microtubules for Cancer Chemotherapy.
Curr Med Chem Anti-Cancer Agents. 2005:5;65-71

[10] Cancer Research UK, Breast Cancer Statistics - Key Facts [updated
April 2010]. Available from:
ue (accessed (04/08/10)

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

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Media Inquiries: Eisai Europe Ltd, Cressida Robson, +44-7908-314-155, Cressida_Robson at eisai.net; Ingenda Communications, Robyn Cabarrao, +44-7913-216-896, RCabarrao at ingendacommunications.com

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