EMA Approves Eisai's Lenvatinib for Accelerated Assessment in Radioiodine-Refractory Differentiated Thyroid Cancer

Hatfield, England (ots/PRNewswire) -

FOR EU MEDIA ONLY: NOT FOR SWISS MEDIA

Accelerated Review Demonstrates the Importance of Lenvatinib for
This Therapeutic Area

The European Medicines Agency (EMA) has approved Eisai's request
for accelerated assessment of the investigational oral multiple
receptor tyrosine kinase (RTK) inhibitor lenvatinib, for the
treatment of patients with progressive radioiodine-refractory,
differentiated thyroid cancer (RR-DTC). Lenvatinib is expected to be
filed imminently and could become a first in a new class of tyrosine
kinase inhibitors.

Thyroid cancer is the most common endocrine malignancy.[1] In
Europe alone, over 50,000 cases of thyroid cancer were diagnosed in
2012.[2] Although treatment is possible for most types of thyroid
cancer, there remains an unmet need for treatment options once the
disease has progressed.

Lenvatinib is an oral multiple receptor tyrosine kinase (RTK)
inhibitor with a novel binding mode that selectively inhibits the
kinase activities of vascular endothelial growth factor receptors
(VEGFR), in addition to other proangiogenic and oncogenic
pathway-related RTKs including fibroblast growth factor receptors
(FGFR), the platelet-derived growth factor (PDGF) receptor
PDGFRalpha, KIT and RET that are involved in tumour proliferation.
This potentially makes lenvatinib a first-in-class treatment,
especially given that it simultaneously inhibits the kinase
activities of FGFR as well as VEGFR.[3],[4],[5] Lenvatinib received
orphan drug designation (ODD) for the treatment of follicular and
papillary thyroid cancer from the European Commission in April 2013.

"We are delighted that lenvatinib will undergo accelerated
assessment by the EMA. The EMA recognises that RR-DTC is a
challenging disease to treat and there is an urgent need for
effective treatment options. At time of filing we will be another
step closer to providing an innovative therapy to people with
advanced thyroid cancer," said Gary Hendler, President & CEO Eisai
EMEA and President, Eisai Oncology Global Business Unit.

The EU marketing authorisation application will be based on the
results of the Phase III SELECT (Study of (E7080) LEnvatinib in
Differentiated Cancer of the Thyroid) trial of lenvatinib which
showed that, progression free survival (PFS) with lenvatinib was
extended significantly compared to placebo (Hazard Ratio (HR)=0.21,
[99% CI, 0.14-0.31]; p<0.0001). The median PFS with lenvatinib and
placebo were 18.3 months and 3.6 months, respectively.[6]

The SELECT study was a multicentre, randomised, double-blind,
placebo-controlled Phase III study to compare the PFS of patients
with RR-DTC and radiographic evidence of disease progression within
the prior 13 months, treated with once-daily, oral lenvatinib versus
placebo. Secondary endpoints of the study included overall response
rate (ORR), overall survival (OS) and safety. The study enrolled 392
patients in over 100 sites in Europe, North and South America and
Asia and was conducted by Eisai in collaboration with the SFJ
Pharmaceuticals Group. Eisai hopes to receive file application in the
next few months.

The development of lenvatinib underscores Eisai's human health
care mission, the company's commitment to innovative solutions in
disease prevention, cure and care for the health and wellbeing of
people worldwide. Eisai is committed to the therapeutic area of
oncology and addressing the unmet medical needs of patients and their
families.

Notes to Editors

Lenvatinib (E7080)

Lenvatinib, discovered and developed by Eisai, is an oral multiple
receptor tyrosine kinase (RTK) inhibitor with a novel binding mode
that selectively inhibits the kinase activities of vascular
endothelial growth factor receptors (VEGFR), in addition to other
proangiogenic and oncogenic pathway-related RTKs including fibroblast
growth factor receptors (FGFR), the platelet-derived growth factor
(PDGF) receptor PDGFRalpha, KIT and RET that are involved in tumour
proliferation.[7],[8] This potentially makes lenvatinib a
first-in-class treatment, especially given that it simultaneously
inhibits the kinase activities of FGFR as well as VEGFR. It is
currently under investigation as a treatment for thyroid,
hepatocellular carcinoma (Phase III), non-small cell lung cancer
(Phase II) and other solid tumour types.

About SELECT[6]

The SELECT (Study of (E7080) LEnvatinib in Differentiated Cancer
of the Thyroid) study was a multicentre, randomised, double-blind,
placebo-controlled Phase III study to compare the PFS of patients
with RR-DTC and radiographic evidence of disease progression within
the prior 13 months, treated with once-daily, oral lenvatinib (24mg)
versus placebo. The study enrolled 392 patients in over 100 sites in
Europe, North and South America and Asia and was conducted by Eisai
in collaboration with the SFJ Pharmaceuticals Group.

Participants were stratified by age (less than or equal to65, >65
years), region and less than or equal to1 prior VEGFR-targeted
therapies and randomised 2:1 to either lenvatinib or placebo therapy
(24mg/d, 28-d cycle). The primary endpoint was PFS assessed by
independent radiologic review. The secondary endpoints of the study
included overall response rate (ORR), overall survival (OS) and
safety. Rates of complete response were 1.5% (4 patients) for the
lenvatinib group and zero in the placebo group. The results for
partial response were 63.2% (165 patients) in the lenvatinib group
and 1.5% (2 patients) in the placebo arm. The median exposure
duration was 13.8 months for lenvatinib and 3.9 months for placebo
and the median time to response for lenvatinib was 2.0 months. Median
OS has not yet been reached.

The five most common lenvatinib treatment-related adverse events
(TRAEs) of any grade were hypertension (67.8%), diarrhea (59.4%),
decreased appetite (50.2%), weight loss (46.4%) and nausea (41.0%).
TRAEs of Grade 3 or higher (Common Terminology Criteria for Adverse
Events) included hypertension (41.8%), proteinuria (10.0%), weight
loss (9.6%), diarrhoea (8.0%), and decreased appetite (5.4%).

About Thyroid Cancer

Thyroid cancer refers to cancer that forms in the tissues of the
thyroid gland, located at the base of the throat near the trachea.[9]
It is more common in women than in men and most are in their 40s or
50s at time of diagnosis. [1] Thyroid cancer is the most common
endocrine malignancy and global figures show that its incidence has
increased significantly over the last 50 years. [1]

The most common types of thyroid cancer, papillary and follicular
(including Hurthle cell), are classified as differentiated thyroid
cancer (DTC) and account for approximately 90% of all cases.[10] The
remaining cases are classified as either medullary (5-7% of cases) or
anaplastic (1-2% of cases).[11]While most DTC patients are curable
with surgery and radioactive iodine treatment, the prognosis for
those patients who do not respond is poor.[12] There are limited
treatment options for this difficult-to-treat, life-threatening and
treatment-refractory form of thyroid cancer.[13]

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
management
- 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 Austria, Belgium, Czech
Republic, Denmark, Finland, France, Germany, Iceland, Ireland, Italy,
the Middle East, the Netherlands, Norway, Portugal, Russia, Slovakia,
Spain, Switzerland, Sweden, and the United Kingdom.

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

References

1. Brito J et al. BMJ 2013; 347

2. Thyroid Cancer. International Agency for Research on Cancer.
http://eco.iarc.fr/eucan/Cancer.aspx?Cancer=35 (last accessed: July
2014)

3. Data on file, Eisai.Co.Ltd

4. Zuccotto F et al. J. Med. Chem. 2010, 53, 2681-2694.

5. Liao et al. Journal of Medicinal Chemistry, 2007, 50;3:409-422

6. Schlumberger M et al. A phase 3, multicenter, double-blind,
placebo-controlled trial of lenvatinib (E7080) in patients with
131I-refractory differentiated thyroid cancer (SELECT). ASCO 2014
abstract #E450

7. Matsui J, et al. Clin Cancer Res 2008;14:5459-65

8. Matsui J, et al. Int J Cancer 2008;122:664-71

9. National Cancer Institute at the National Institute of Health h
ttp://www.cancer.gov/cancertopics/pdq/treatment/thyroid/Patient/page1
/AllPages#1 (last accessed: July 2014)

10. Cooper DS et al. Thyroid. 2009;19(11):1167-1214

11. Thyroid Cancer Basics. 2011. http://www.thyca.org

12. Gild M et al. Multikinase inhibitors: a new option for the
treatment of thyroid cancer. Nature Reviews Endocrinology. 2011; 7:
617-624

13. Bible K, et al. Lancet Oncology 2010;11(10):962-972

Job code: Lenvatinib-UK0032

Date of preparation: July 2014

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

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