Halaven® (eribulin) Receives European Commission Marketing Authorisation Approval (MAA) for Advanced Breast Cancer After Only

   Halaven® (eribulin) Receives European Commission Marketing Authorisation
 Approval (MAA) for Advanced Breast Cancer After Only One Prior Chemotherapy

  PR Newswire

  HATFIELD, England, July 3, 2014

HATFIELD, England, July 3, 2014 /PRNewswire/ --

FOR EU MEDIA ONLY, EXCLUDING SWISS, GERMAN, UK AND NORDIC MEDIA 

                                      

  New, earlier use indication to benefit thousands of women across Europe 

The European Commission (EC) has issued Marketing Authorisation Approval (MAA)
for Halaven ^® (eribulin) in the treatment of patients with locally advanced
or metastatic breast cancer (MBC) who have progressed after at least one
chemotherapeutic regimen for advanced disease. Prior therapy should have
included an anthracycline and a taxane in either the adjuvant or metastatic
setting, unless patients were not suitable for these treatments. ^[ ^1]

"Eribulin remains the only single-agent chemotherapy proven to prolong overall
survival in women with pre-treated metastatic breast cancer. Therefore, it's
crucial that we have the flexibility to offer them eribulin as early as
possible in the course of their disease. The survival benefit seen in women
with HER2 negative cancers is particularly important as they represent about
80% of all women with breast cancer," commented Dr Chris Twelves, Professor of
Clinical Cancer Pharmacology and Oncology, and Honorary Consultant in Medical
Oncology at the University of Leeds and St James's Institute of Oncology.

The MAA for eribulin is based on clinical evidence from two global Phase III
trials; EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Treatment of
Physician's Choice Versus Eribulin) ^[ ^2] and study 301. ^[ ^3] These studies
involved more than 1,800 women.

EMBRACE showed eribulin can prolong median overall survival in heavily
pre-treated women with MBC compared to women receiving an alternative
treatment of physician's choice by 2.7 months (13.2 vs 10.5 HR 0.81 (95% CI
0.67, 0.96) nominal p=0.014). The most commonly reported adverse reactions in
the eribulin study arm were fatigue (asthenia), a decrease in
infection-fighting white blood cells (neutropenia), hair loss (alopecia),
numbness and tingling in arms and legs (peripheral neuropathy), nausea and
constipation. ^[ ^1 ^] EMBRACE is one of only 25 studies to demonstrate a
significant extension in overall survival (as primary or secondary endpoint)
in MBC in the last 40 years. ^[ ^4]

Study 301, a head-to-head trial of eribulin vs capecitabine, had a co-primary
endpoint of overall survival and progression-free survival. The study
demonstrated a trend favouring improved overall survival with eribulin
compared to capecitabine in the intention-to-treat population, although the
improvement was not statistically significant. ^[ ^3 ^]  Women treated with
eribulin had a median overall survival of 15.9 months versus 14.5 months with
capecitabine (HR 0.879; 95% CI: 0.770-1.003; p=0.056). ^[ ^3 ^] For women with
human epidermal growth factor receptor 2 (HER2) negative metastatic breast
cancer, overall survival was 15.9 months for eribulin vs 13.5 months for
capecitabine (HR 0.838; 95% CI: 0.715-0.983). ^[ ^3 ^] The most common adverse
events reported for eribulin and capecitabine (≥20% all grades) were
neutropenia (54% vs 16%), hand-foot syndrome (<1% vs 45%) alopecia (35% vs
4%), leukopenia (31% vs 10%), diarrhoea (14 vs 29%) and nausea (22% vs 24%),
respectively. ^[ ^3 ^]

"Eisai is very pleased that eribulin is now indicated for use in women with
locally advanced or metastatic breast cancer who have progressed after at
least one chemotherapeutic regimen for advanced disease. This earlier use of
eribulin will allow more women across Europe to receive the survival benefits
that treatment with eribulin may provide. As a company, we continue to be
committed to broadening access to eribulin to help redress the inequality
between early and advanced breast cancer outcomes," said Gary Hendler,
President Eisai Global Oncology Business Unit.

Eisai is dedicated to discovering, developing and producing innovative
oncology therapies that can make a difference and impact the lives of women
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.

Notes to Editors 

Halaven ^®  (eribulin) 

Eribulin is a non-taxane, microtubule dynamics inhibitor.Eribulin belongs to a
class of antineoplastic agents, the halichondrins, which are natural products,
isolated from the marine sponge Halichondria okadai. It is believed to work by
inhibiting the growth phase of microtubule dynamics which prevents cell
division.

Global Phase III Clinical Study 305 (EMBRACE) ^[ ^1 ^]

EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Treatment of
Physician's Choice (TPC) Versus Eribulin E7389) was an open-label, randomised,
global, multi-centre, parallel two-arm study designed to compare overall
survival in women treated with eribulin versus a TPC arm. TPC was 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. The study included 762 participants
with metastatic breast cancer who previously had been treated with at least
two and a maximum of five prior chemotherapies, including an anthracycline and
a taxane. The vast majority (96%) of participants in the TPC arm received
chemotherapy.

In the total phase III EMBRACE study population, eribulin was shown to prolong
median overall survival in heavily pre-treated women with metastatic breast
cancer compared to women receiving TPC by 2.7 months (13.2 vs 10.5 HR 0.81
(95% CI 0.67, 0.96) nominal p=0.014). A pre-planned analysis of participants
from Region 1 of the study (North America/Western Europe/Australia) showed a
significant median overall survival benefit of eribulin over TPC of 3.0 months
(nominal p=0.031).

The most commonly reported adverse reactions among people treated with
eribulin in the EMBRACE study were fatigue (asthenia), a decrease in
infection-fighting white blood cells (neutropenia), hair loss (alopecia),
numbness and tingling in arms and legs (peripheral neuropathy), nausea and
constipation. Peripheral neuropathy was the most common adverse event leading
to discontinuation from eribulin, occurring in less than 5% of the women
involved in the EMBRACE trial. Neutropenia only led to eribulin
discontinuation for 0.6%. Death due to serious side effects, discontinuation
and dose interruptions to treatment were lower in the eribulin arm of the
trial compared with the TPC arm.

Global Phase III Study 301  ^[ ^3 ^]

Study 301 was an open-labelled, randomised, two-parallel-arm, multicentre
study of eribulin versus capecitabine in 1,102 women with locally advanced or
metastatic breast cancer previously treated with anthracyclines and taxanes,
either in the (neo) adjuvant setting or for locally advanced or metastatic
disease. Women in the study received zero to two previous chemotherapies for
advanced disease.

The study opened in 2006 and the last patient was randomised in 2010. Patients
were randomised to treatment with either eribulin 1.23mg/m ^2 (administered
intravenously over two to five minutes on days 1 and 8, every 21 days) or
capecitabine 2.5g/m ^2 (administered orally twice daily in two equal doses on
days 1 to 14, every 21 days).

Study 301 had a co-primary endpoint of OS and PFS. The study demonstrated a
trend favouring improved OS with eribulin compared to capecitabine in the ITT
population, although the improvement was not statistically significant. Women
treated with eribulin had a median OS of 15.9 months (HR 0.879; 95% CI:
0.770-1.003; p=0.056) versus 14.5 months with capecitabine. The trial did not
meet the pre-specified endpoint for progression-free survival, with 4.1 and
4.2 months for eribulin and capecitabine respectively (HR 1.079; 95% CI:
0.932-1.250; p=0.305).

1-,2- and 3- year overall survival rates for eribulin versus capecitabine
showed an early improvement which was maintained throughout the study (1 year,
64.4% eribulin vs 58.0% capecitabine (P=0.0351), 2 year 32.8% eribulin vs
29.8% capecitabine (P=0.324), 3 year, 17.8% eribulin vs 14.5% capecitabine
(P=0.175).

Unlike studies conducted today, study 301 included all women regardless of
their human epidermal growth factor receptor 2 (HER2), oestrogen receptor (ER)
or progesterone receptor (PR) status. Patients are usually tested for their
HER2 status as there are now effective treatments specifically for patients
with the HER2 mutation. HER2 positive patients would generally be treated
with anti-HER2 positive targeted therapy. For women with HER2 negative
metastatic breast cancer (n=755), OS was 15.9 months for eribulin vs 13.5
months for capecitabine (HR 0.838; 95% CI: 0.715-0.983). In the HER2 positive
population, OS was 14.3 months for eribulin vs 17.1 months for capecitabine
(HR; 95% 0.965; CI: 0.688-1.355).

Adverse events in Study 301 were consistent with the known profile of both
drugs.

Metastatic Breast Cancer 

Over 300,000 women are diagnosed with breast cancer in Europe every year, of
whom about one third subsequently develop metastatic disease. ^[5] ^, ^[6]
Metastatic disease is an advanced stage of the disease that occurs when cancer
spreads beyond the breast to other parts of the body.

Eisai in Oncology 

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,
and biologic and supportive care agents for cancer across multiple
indications.

About Eisai 

Eisai is one of the world's leading research and development (R&D) based
pharmaceutical companies and we define our 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:

  *Oncology including: anticancer therapies; tumour regression, tumour
    suppression, antibodies, etc.
  *Neuroscience, including: Alzheimer's disease, epilepsy, pain and weight
    loss
  *Vascular/Immunological reaction including: thrombocytopenia, rheumatoid
    arthritis, psoriasis, inflammatory bowel disease

With operations in the U.S., Asia, Europe and its domestic home market of
Japan, Eisai employs more than 10,000 people worldwide. From its EMEA
Knowledge Centre in Hatfield, UK, Eisai has recently expanded its business
operations to include Europe, the Middle East, Africa, Russia and Oceania
(EMEA). Eisai EMEA has sales and marketing operations in over 20 markets,
including the United Kingdom, France, Germany, Italy, Spain, Switzerland,
Sweden, Ireland, Austria, Denmark, Finland, Norway, Portugal, Czech Republic,
Slovakia, the Netherlands, Belgium, Luxembourg, Russia and the Middle East.

For further information please visit our web site http://www.eisai.co.uk

References 

1. European Commission Implementing Decision for Halaven received June 2014

2. Cortes J, O'Shaughnessy J, Loesch D, et al. Eribulin monotherapy versus
treatment of physician's choice in patients with metastatic breast cancer
(EMBRACE): a phase 3 open-label randomised study. The Lancet. 2011;377:914-923

3. Kaufman P, Awada A, Twelves C et al. A Phase III, open-label, randomised,
multicenter study of eribulin mesylate versus capecitabine in patients with
locally advanced or metastatic breast cancer previously treated with
anthracyclines and taxanes. Presented at 2012 CTRC-AACR San Antonio Breast
Cancer Symposium

4. Data on File ERI-099 Improvement in Overall Survival in Metastatic Breast
Cancer

5. World Health Organisation. Atlas of Health in Europe. 2003. World Health
Organization, Regional Office of Europe, Copenhagen, Denmark.

6. Cancer Research UK. Breast cancer incidence statistics.
http://www.cancerresearchuk.org/cancer-info/cancerstats/types/breast/incidence/#world
[
http://www.cancerresearchuk.org/cancer-info/cancerstats/types/breast/incidence
]. Last accessed May 2014

Date of preparation: July 2014 Job code: Halaven-UK0302

Contact: Media Enquiries: Eisai Europe Ltd : Cressida Robson / Ben Speller ,
+44(0)7908 314 155 / +44(0)7947 231 513, Cressida_Robson@eisai.net,
Ben_Speller@eisai.net ; Tonic Life Communications : Siobhan Reilly / April
Kenneally, +44(0)207 798 9999 / +44(0)207 798 9263,
siobhan.reilly@toniclc.com, april.kenneally@toniclc.com
 
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