Federal Joint Committee (G-BA) Publishes Benefit Assessment Report on Lenvima® (Lenvatinib)

Hatfield, England (ots/PRNewswire) -

NOT FOR US OR SWISS OR AUSTRIAN MEDIA, PLEASE SEE SPECIFIC PRESS
RELEASE IF AVAILABLE

Report summarises clinical data and results for the advanced
thyroid cancer treatment

Federal Joint Committee (G-BA) today publishes the benefit
assessment report for Lenvima(R) (lenvatinib) for people with
radioactive iodine refractory differentiated thyroid cancer (RAI
refractory DTC).

The G-BA will now accept comments from concerned parties,
including scientific and medical expert associations, via written
statements on the benefit assessment report until 22 October 2015.
Eisai will make a formal response to the benefit assessment report in
due course.

"Eisai is confident that the G-BA will appreciate the significant
therapeutic benefits lenvatinib offers to people in Germany. We will
move quickly to provide our comments on a number of important areas
in the benefit assessment report and look forward to the discussions
in the forthcoming oral hearing with experts," commented Gary
Hendler, President and CEO, Eisai EMEA and President, Eisai Oncology
Global Business Unit.

"I hope that the G-BA will see the potential that lenvatinib
represents for people living with advanced thyroid cancer, a
difficult to treat condition with few treatment options. It was
crucial that this treatment was made available to people in Germany
earlier this year, so that patients living with radioactive iodine
refractory differentiated thyroid cancer could begin to experience
the benefits it offers," commented Professor Christoph Reuter, Clinic
for Haematology, Haemostaseology and Oncology, Hannover Medical
School.

Lenvatinib has been approved for the treatment of refractory
thyroid cancer in the United States, Europe and Japan, and has been
submitted for regulatory approval in Switzerland, South Korea,
Canada, Singapore, Russia, Australia and Brazil. Lenvatinib was
granted Orphan Drug Designation in Japan for thyroid cancer, in the
United States for treatment of follicular, medullary, anaplastic, and
metastatic or locally advanced papillary thyroid cancer and in Europe
for follicular and papillary thyroid cancer.

While thyroid cancer is relatively rare, over the past few decades
the incidence of the disease is rising rapidly across the whole of
Europe.[1],[2] In 2012 there were approximately 5,229 cases in
Germany.[1] More prevalent in women than men, at a ratio of 2 to 1,
thyroid cancer is the most common endocrine malignancy.[3]

The G-BA report references the National Comprehensive Cancer
Network (NCCN), an alliance of the world's leading cancer centres,
which recently updated its guidelines to recommended lenvatinib as
the preferred treatment for radioactive iodine refractory
differentiated thyroid cancer due to its response rate. The NCCN
said, "The NCCN Panel feels that lenvatinib is the preferred agent in
this setting based on a response rate of 65% for lenvatinib when
compared with 12% for sorafenib, although these agents have not been
directly compared."[4]

The G-BA report also provides information on the efficacy of
lenvatinib. Lenvatinib demonstrates significantly prolonged
progression-free survival (PFS) in RAI refractory DTC versus placebo.
Lenvatinib shows a median 18.3 months progression free survival PFS
versus 3.6 months for placebo (hazard ratio [HR] 0.21; 99% confidence
interval 0.14-0.31, p<0.0001). In addition, the study underlines the
rapid response of lenvatinib, with a median time to first objective
response of two months. The SELECT study published in the New England
Journal of Medicine, is a randomised, double-blind, multicentre trial
for people with progressive radioactive iodine refractory
differentiated thyroid cancer (n=392).[5] Lenvatinib significantly
improves objective response rate versus placebo (64.8% versus 1.5%;
p<0.0001). For lenvatinib, the most common treatment related adverse
events were hypertension, diarrhoea, fatigue, decreased appetite,
decreased weight, and nausea.

An updated analysis from the SELECT study has shown that
lenvatinib significantly improves overall survival versus placebo in
patients with progressive radioactive iodine refractory
differentiated thyroid cancer (RAI Refractory-DTC) (HR=0.53; 95% CI:
0.34, 0.82, nominal p=0.0051). These data was presented at the
recent European Cancer Congress (ECC) in Vienna.[6]

Lenvatinib, discovered and developed by Eisai, is an oral
molecular tri-specific targeted therapy that possesses a potent
selectivity and a binding mode different to other tyrosine kinase
inhibitors (TKI). Lenvatinib simultaneously inhibits the activities
of several different molecules including vascular endothelial growth
factor receptors (VEGFR), fibroblast growth factor receptors (FGFR),
rearranged during transfection tyrosine kinase (RET), Tyrosinkinase
KIT (KIT) and platelet-derived growth factor receptors (PDGFR). This
potentially makes lenvatinib the first TKI that simultaneously
inhibits the kinase activities of FGFR 1-4 as well as VEGFR
1-3.[7],[8] In addition, lenvatinib was found to have a new Type V
binding mode of kinase inhibition that is distinct from existing
compounds.[9],[10]

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

Notes to Editors

About Lenvatinib

Eisai is currently conducting clinical studies of lenvatinib in
several types of cancer including hepatocellular carcinoma (Phase
III), renal cell carcinoma (Phase II), non-small cell lung cancer
(Phase II) and endometrial cancer (Phase II).

About Lenvatinib's Novel Binding Mode (Type V)[9],[10]

Kinase inhibitors are categorized into several types (Type I to
Type V) depending on the binding site and the conformation of the
targeted kinase in complex with them. Most of the currently approved
tyrosine kinase inhibitors are either Type I or Type II, however
according to X-ray crystal structural analysis, lenvatinib was found
to possess a new Type V binding mode of kinase inhibition that is
distinct from existing compounds. In addition, lenvatinib was
confirmed via kinetic analysis to exhibit rapid and potent inhibition
of kinase activity, and it is suggested that this may be attributed
to its novel binding mode.

About SELECT[11]

The SELECT (Study of (E7080) LEnvatinib in Differentiated Cancer
of the Thyroid) study is a multicentre, randomised, double-blind,
placebo-controlled Phase III study to compare the PFS of patients
with radioactive iodine refractory differentiated thyroid cancer 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 six most common lenvatinib treatment-related adverse events
(TRAEs) of any grade were hypertension (67.8%), diarrhea (59.4%),
fatigue (59.0%), 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%).

Subgroup analyses presented at the European Thyroid Association
Annual Meeting in September 2014 showed that lenvatinib maintained a
PFS benefit in all pre-defined subgroups of people with progressive
radioiodine-refractory differentiated thyroid cancer. In particular,
the PFS benefit observed in 195 people with progressive
radioiodine-refractory differentiated thyroid cancer in Europe
(lenvatinib n=131 and placebo n=64) was similar to the PFS of overall
study population (HR=0.24, [95% CI, 0.16-0.35]).[12] The median PFS
with lenvatinib and placebo were 18.7 months and 3.7 months
respectively.[12]

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.[13] It is more common in women than in men and most are in
their 40s or 50s at time of diagnosis.[14]

Thyroid cancer affects more than 52,000 people in Europe each
year.[1] The incidence of thyroid cancer has increased significantly
in the last decade by 69% and 65% in men and women, respectively. 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.[15] The
remaining cases are classified as either medullary (5-7% of cases) or
anaplastic (1-2% of cases).[16]

RAI Refractory-DTC is a rare, difficult-to-treat type of cancer,
characterised by aggressive growth and spread. While most DTC
patients are curable with surgery and radioactive iodine treatment,
the prognosis for those patients who do not respond is poor. [15]
There are limited treatment options for this life-threatening and
treatment-refractory form of thyroid cancer.[16]

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 EUCAN 2015.
http://eu-cancer.iarc.fr/EUCAN/Cancer.aspx?Cancer=35 Accessed: June
2015

2 Kilfoy BA et al. Cancer Causes Control. 2009 Jul; 20(5):525-31

3 Butterfly Thyroid Cancer Trust. About Thyroid Cancer. Available
at: http://www.butterfly.org.uk/about.htm Accessed: June 2015

4 NCCN Flash Update, page 10. Available at: https://www.sumocancer
.org/wp-content/uploads/2015/07/Q2-NCCN-Flash-Update-Report-7.8.2015.
pdf Accessed: September 2015

5 Schlumberger M et al. Lenvatinib versus placebo in radioiodine
refractory differentiated thyroid cancer. NEJM 2015; 372: 621-630.
Available at http://www.nejm.org/doi/full/10.1056/NEJMoa1406470
Accessed: June 2015

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

7 Matsui J, et al. Int J Cancer 2008; 122:664-671

8 Okamoto K, et al. Distinct Binding Mode of Multikinase Inhibitor
Lenvatinib Revealed by Biochemical Characterization. ACS Med. Chem.
Lett 2015; 6:89-94

9 Newbold K et al. Phase 3 study of (E7080) Lenvatinib in
Differentiated Cancer of the Thyroid (SELECT): Results and subgroup
analysis of patients from Europe. Presented as a digital poster at
ETA 2014.

10 Wirth L et al. 2015; Open-Label Extension Phase Outcomes of the
Phase 3 Select Trial of Lenvatinib in Patients with 131I-Refractory
Differentiated Thyroid Cancer. Endocrine Reviews; 36;2: Abstract
0R44-6. Available at: http://press.endocrine.org/doi/abs/10.1210/endo
-meetings.2015.THPTA.6.OR44-6 Accessed: September 2015

11 Schlumberger M et al. Relationship Between Thyroid-Stimulating
Hormone Levels and Outcomes from the Randomized, Double-Blind, Phase
3 Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid
(SELECT).Available at:
https://endo.confex.com/endo/2015endo/webprogram/Paper20459.html
Accessed: September 2015

12 National Cancer Institute at the National Institute of Health.
Available at: http://www.cancer.gov/cancertopics/pdq/treatment/thyroi
d/Patient/page1/AllPages#1 Accessed: September 2015

13 Brito J et al. BMJ 2013; 347

14 Cabanillas ME., Dadu R. Optimizing therapy for radioactive
iodine-refractory differentiated thyroid cancer : Current state of
the art and future directions. Minerva Endocrinol. 2012 Dec;
37(4):335-356.

15 Thyroid Cancer Basics. 2011. Available at: http://www.thyca.org
Accessed: June 2015

16 Pacini F et al. ESMO Guidelines Working Group. Ann Oncol.
2012;23 (suppl 7) :vii110-vii119.

Date of preparation: October 2015
Job code: Lenvima-UK0049

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

Contact:
Media Enquiries: Eisai: Cressida Robson / Ben Speller,
+44(0)7908-314-155 / +44(0)7908-409416, Cressida_Robson@eisai.net /
Ben_Speller@eisai.net. Tonic Life Communications: Alex Davies / Deepa
Patel, +44-(0)7720-496-472 / +44-(0)7725-440-867,
Alex.davies@toniclc.com /
Deepa.Patel@toniclc.com