Halaven® (Eribulin) Receives Positive CHMP Opinion in Advanced Liposarcoma Following Significant Phase III Data

Hatfield, England (ots/PRNewswire) -

FOR EU MEDIA ONLY: NOT FOR SWISS AND AUSTRIAN MEDIA

Variation to extend indication of eribulin for treatment of
adult patients with unresectable liposarcomas who have received prior
anthracycline containing therapy (unless unsuitable) for advanced or
metastatic disease[1]

Positive opinion for licence extension to Halaven® (eribulin) from
the European Medicines Agency's Committee for Medicinal Products for
Human Use (CHMP) is based on pivotal Phase III data which show a
median 7.2 month increase in overall survival compared to dacarbazine
(15.6 months versus 8.4 months, HR = 0.511; 95% CI 0.346-0.753;
P=0.0006) for people with unresectable advanced or metastatic
liposarcomas.[1] Eribulin is the first and only single agent therapy
to show a significant survival advantage in this type of soft tissue
sarcoma.[2]

"Eribulin has been shown to extend the lives of adults with
specific types of progressive soft tissue sarcoma, which are rare and
have a high rate of mortality. This positive opinion is welcomed by
sarcoma specialists in Europe, who have few options to treat these
patients. These data are a clinically meaningful result given the
significant unmet need. This is the first and only time that we have
been able to demonstrate an overall survival benefit in soft tissue
sarcoma in a large Phase III trial, which mirrors the results for
eribulin in advanced breast cancer," said Patrick Schöffski, Head of
the Department of General Medical Oncology, University Hospitals
Leuven, Belgium.

Eribulin shows a median overall survival improvement of 2.6 months
(13.5 months versus 11.5 months) in patients with leiomyosarcomas or
liposarcomas (L-type soft tissue sarcomas) when compared with
dacarbazine, an active treatment option (HR=0.768, 95% CI
0.618-0.954; P=0.017).[2] There were no unexpected or new safety
findings; the toxicity profile is consistent with the known safety
profile of eribulin.[2] The pivotal study results were published in
The Lancet, February 2016.[2]

Eribulin is a microtubule-dynamics inhibitor, structurally
modified analogue of halichondrin B, originally isolated from the
marine sponge Halichondria okadai. Its mode of action is distinct
from other tubulin inhibitors and involves binding to specific sites
on the growing positive ends of microtubules to inhibit their growth.
Eribulin also induces vascular remodelling, suppresses migration and
invasion of cancer cells, and reverses the epithelial-to-mesenchymal
transition in many cancer cell lines.

Only 50% of people with soft tissue sarcomas are expected to live
five years.[3] 29,000 people are diagnosed with soft tissue sarcomas
each year, approximately 1% of all cancers diagnosed in Europe.[4]
Liposarcomas (adipocytic sarcomas) originate in fat cells and can
occur anywhere in the body.[5]

"For the first time, people with liposarcoma, a rare and difficult
to treat cancer, have an option that can significantly extend their
lives. This is the second form of cancer in which eribulin has
demonstrated an overall survival cancer benefit, and we remain
committed to developing eribulin's potential for people with cancer,
their family and carers," comments Gary Hendler, President and
Commercial Director, Eisai Global Oncology Business Unit and Chairman
& CEO, Eisai EMEA.

In January 2016 the Food and Drug Administration (FDA) approved
eribulin for the treatment of people in the US with unresectable or
metastatic liposarcoma who have received a prior
anthracycline-containing regimen. Licence was granted in Japan to
extend the indication of eribulin to treat patients with soft tissue
sarcomas in February 2016.

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.

Notes to Editors

Halaven® (eribulin)

Eribulin is the first in the halichondrin class of microtubule
dynamics inhibitors with a novel mechanism of action. Structurally
eribulin is a simplified and synthetically produced version of
halichondrin B, a natural product isolated from the marine sponge
Halichondria okadai. Eribulin is believed to work by inhibiting the
growth phase of microtubule dynamics which prevents cell division.

Eribulin is currently indicated for the treatment of women with
locally advanced or metastatic breast cancer 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.[6]

About Soft Tissue Sarcomas

Soft tissue sarcoma is a collective term for a diverse group of
malignant tumours.

Leiomyosarcomas and liposarcomas make up around 30% of all cases
of soft tissue sarcomas[7] and develop from cells in the tissues that
surround the body such as fat, muscle, nerves, fibrous tissues and
blood.[4] Leiomyosarcomas form from cells called smooth muscle and
can start anywhere in the body.[4]

Unlike other cancers such as non-small cell lung cancer (NSCLC),
soft tissue sarcomas are mostly diagnosed with localised disease, and
many are amenable to complete surgical removal, yet relapse rates can
be as high as 50 percent.[8] Outcomes for patients with advanced
disease are poor, with median survival around one year or less. Due
to the rarity of these tumours, evidence for prognostic factors is
weak and not well understood.[9]

Global Phase III Clinical Study 309[2]

Study 309 is a randomised, open-label multicentre Phase III study
comparing the efficacy and safety of eribulin mesilate in 452
patients (aged 18 or over).[2]

The primary endpoint of the study was to compare overall survival
between patients treated with eribulin mesilate 1.4 mg/m² (equivalent
to eribulin 1.23mg/m[2]) intravenously on days 1 and 8 and those
treated with dacarbazine (850 mg/m², 1000 mg/m², or 1200 mg/m² [dose
dependent on centre and clinician] intravenously on day 1). The
additional endpoints included progression free survival and quality
of life.[2]

Patients were aged >=18 years with advanced high/intermediate
grade leiomyosarcoma or dedifferentiated, myxoid, round cell or
pleomorphic variants of adipocytic sarcoma (ADI) incurable by surgery
and/or radiotherapy were enrolled. Patients had ECOG status <=2 and
had received >=2 standard systemic treatment regimens including an
anthracycline.[2] Patients were randomized 1:1 to eribulin mesilate
(1.4 mg/m[2], IV on D1 and D8) or dacarbazine (850-1200 mg/m2, IV on
D1) every 21 days until disease progression.[2]

Overall, 452 patients (67% female; 79% <65 years) were randomized
(228 eribulin; 224 dacarbazine). Median OS for eribulin and
dacarbazine was 13.5 and 11.5 months, respectively (HR=0.768, 95% CI
0.618-0.954; P=0.017). PFS was 2.6 months in both arms (HR=0.877, 95%
CI 0.710-1.085; P=0.229). PFS rate at week 12 was 33% and 29% for
eribulin and dacarbazine, respectively.[2] Eribulin had a toxicity
profile consistent with prior experience, with no unexpected or new
safety findings. In this study, the most common adverse events
observed in the eribulin arm were neutropenia, fatigue, nausea,
alopecia and constipation, which is consistent with the known profile
of eribulin.[2]

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 Co., Ltd.

Eisai Co., Ltd. is a leading global research and development-based
pharmaceutical company headquartered in Japan. 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 our human health care (hhc) philosophy. With over 10,000
employees working across our global network of R&D facilities,
manufacturing sites and marketing subsidiaries, we strive to realise
our hhc philosophy by delivering innovative products in multiple
therapeutic areas with high unmet medical needs, including Oncology
and Neurology.

As a global pharmaceutical company, our mission extends to
patients around the world through our investment and participation in
partnership-based initiatives to improve access to medicines in
developing and emerging countries.

For more information about Eisai Co., Ltd., please visit
http://www.eisai.com.

References

1. European Medicines Agency. Summary of Opinion (post
authorisation) Halaven, eribulin April 2016. Available at: http://www
.ema.europa.eu/docs/en_GB/document_library/Summary_of_opinion/human/0
02084/WC500203965.pdf

2. Schöffski P et al. Eribulin versus dacarbazine in previously
treated patients with advanced liposarcoma or leiomyosarcoma: a
randomised, open-label, multicentre, phase 3 trial. The Lancet. 2016

3. National Cancer Institute - http://www.cancer.org/cancer/sarcom
a-adultsofttissuecancer/detailedguide/sarcoma-adult-soft-tissue-cance
r-survival-rates

4. ESMO Guidance. Available at: http://annonc.oxfordjournals.org/c
ontent/25/suppl_3/iii102.full.pdf+html Accessed: November 2015

5. Macmillan. What are soft tissue sarcomas? Available at: http://
www.macmillan.org.uk/Cancerinformation/Cancertypes/Softtissuesarcomas
/Aboutsofttissuesarcomas/Softtissuesarcomas.aspx . Accessed:
November 2015

6. SPC Halaven (updated November 2015). Available at:
http://www.medicines.org.uk/emc/medicine/24382 Accessed: December
2015

7. Cancer Research UK, Soft Tissue Sarcoma Incidence Statistics.
Available at: http://www.cancerresearchuk.org/cancer-info/cancerstats
/types/soft-tissue-sarcoma/incidence/ Accessed: November 2015

8. R. Pollock. Soft Tissue Sarcomas, A Volume in the American
Cancer Society Atlas of Clinical Oncology Series. 2012

9. Fletcher et al. World Health Organization Classification of
Tumours of Soft Tissue and Bone (4th Edition). Lyon: IARC Press, 2013

ots Originaltext: Eisai
Im Internet recherchierbar: http://www.presseportal.de

Contact:
Eisai
Cressida Robson / Ben Speller
+44(0)7908-314-155 / +44-(0)7908-09416
Cressida_Robson@eisai.net / Ben_Speller@eisai.net

Tonic Life Communications
Alex Davies / Callum Haire
+44-(0)7716-324722 / +44-(0)7867-429-637
Alex.Davies@toniclc.com / Callum.Haire@toniclc.com