Kisplyx® (lenvatinib) in Combination with everolimus Receives Positive CHMP Opinion in Advanced Renal Cell Carcinoma

Hatfield, England (ots/PRNewswire) -

FOR EMEA MEDIA ONLY: NOT FOR SWISS/AUSTRIAN JOURNALISTS

Marketing Authorisation Application (MAA) for the use of
lenvatinib in combination with everolimus for the treatment of adult
patients with advanced renal cell carcinoma (RCC) following one prior
vascular endothelial growth factor (VEGF)-targeted therapy

The European Medicines Agency's Committee for Medicinal Products
for Human Use (CHMP) today issued a positive opinion for Kisplyx®
(lenvatinib) in combination with everolimus for the treatment of
adult patients with advanced renal cell carcinoma (RCC) following one
prior vascular endothelial growth factor (VEGF)-targeted therapy.[1]

The opinion was issued following the evaluation of results from a
pivotal Phase II trial, which show lenvatinib plus everolimus
significantly extends progression-free survival in patients with
unresectable advanced renal cell carcinoma versus everolimus
alone.[2] Lenvatinib was granted an accelerated assessment by the
European Medicines Agency in October 2015.

Lenvatinib selectively inhibits the kinase activities of several
different receptors including vascular endothelial growth factor
receptors (VEGFR), fibroblast growth factor receptors (FGFR), RET,
KIT and platelet-derived growth factor receptors (PDGFR).[3]

"This is a positive step forward for people with advanced renal
cell carcinoma. The phase II trial was the first in which these two
types of cancer drugs have been successfully combined in renal cell
carcinoma, and the progression free survival results were
statistically significant," comments Dr Hilary Glen, Beatson West of
Scotland Cancer Centre, Glasgow, UK.

The Phase II study, on which the CHMP opinion is based, shows that
people with advanced renal cell carcinoma who progressed on previous
VEGF therapy treated with the combination of lenvatinib plus
everolimus experienced a median progression-free survival of 14.6
months compared with 5.5 months for those who received everolimus
alone (HR 0.40; 95% CI: 0.24-0.68; p=0.0005).[2] In subgroup analyses
of the Phase II study presented at the American Society of Clinical
Oncology (ASCO) Annual Meeting 2016, progression free survival
benefit is maintained across all subgroups regardless of high risk
poor prognosis renal cancer subgroups (MSKCC risk, baseline tumour
size, metastasis site).[4] For the secondary endpoints, updated
median overall survival in the intent-to-treat study population was
25.5 months in the lenvatinib plus everolimus group compared with
15.4 months in the everolimus group (HR 0.59; 95% CI 0.36 - 0.97;
P=0.065).[4] Adverse events were generally higher for the lenvatinib
plus everolimus combination compared with everolimus alone.[4]The
most common grade 3 treatment emergent adverse events in the
lenvatinib plus everolimus group included constipation (37%),
diarrhoea (20%), fatigue or asthenia (14%) and hypertension (14%).
The most commons grade 3 TEAEs in the everolimus group included
anaemia (12%), dyspnoea (8%), hypertriglyceridaemia (8%) and
hyperglycaemia (8%).[4]

Clear cell renal cell carcinoma accounts for approximately 80-90%
of all kidney malignancies. Renal cell carcinoma (RCC) represents
2-3% of all cancer cases, with the highest incidence in Western
countries. During the last two decades, until recently, there has
been about a 2% increase in incidence of RCC worldwide.[5]

"Eisai continues to be committed to the discovery and development
of treatments for cancers like advanced renal cell carcinoma.
Lenvatinib in combination with everolimus is the first proven
combination treatment to treat patients following one prior vascular
endothelial growth factor (VEGF)-targeted therapy. The very real
treatment benefit of the combination provides patients with an
additional treatment option proven to have a beneficial impact on
progression free survival," comments Gary Hendler, Chief Commercial
Officer Oncology Business Group, Chairman and CEO EMEA.

The effect of the combination of lenvatinib plus everolimus in
human renal cell carcinoma xenograft models (a graft of tissue or
cells from one species to an unlike species) was also demonstrated in
a second study presented at the American Association of Cancer
Research in April 2016.[6] Results indicate that lenvatinib in
combination with everolimus causes significant antitumour effects
through the potent antiangiogenic activity of lenvatinib and direct
antitumour activity of everolimus.

Lenvatinib, discovered and developed by Eisai, is an oral
molecular targeted therapy that possesses a potent selectivity and a
new Type V binding mode of kinase inhibition different to that of
other tyrosine kinase inhibitors (TKI).[7]

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

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's Novel Binding Mode (Type V)[7]

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
small molecule kinase inhibitors are either Type I or Type II,
however lenvatinib was found to possess a new binding mode (Type V)
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.[7]

About Everolimus

Everolimus is a selective mTOR (mammalian target of rapamycin)
inhibitor. mTOR is a key serine-threonine kinase, the activity of
which is known to be upregulated in a number of human cancers.[8]

About Advanced Renal Cell Carcinoma

Renal cell carcinoma originates in the lining of the tubules,[9]
the very small tubes in the kidney along with other parts of the
nephron are involved in the blood filtration process to remove waste
products.[10]

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) Lenvatinib, July 2016.

2. Motzer R, et al. Randomized phase 2 three-arm trial of
lenvatinib, everolimus, and the combination in patients with
metastatic renal cell carcinoma. The Lancet Oncology 2015;16:1473-82.
Available athttp://www.thelancet.com/journals/lanonc/article/PIIS1470
-2045(15)00290-9/abstract . Last accessed: June 2016

3. Matsui J, et al. E7080, a novel inhibitor that targets multiple
kinases, has potent antitumor activities against stem cell factor
producing human small cell lung cancer H146, based on angiogenesis
inhibition. Int J Cancer 2008;122:664-671

4 Hutson T, et al. Subgroup analyses from the phase 2 trial of
lenvatinib (LEN), everolimus (EVE), and LEN+EVE in metastatic renal
cell carcinoma (mRCC). American Society for Clinical Oncology annual
meeting 2016; Poster # 175

5. Ljungberg et al. Guidelines on Renal Cell Carcinoma. Available
at: http://uroweb.org/wp-content/uploads/10-Renal-Cell-Carcinoma_LR-L
V2-2015.pdf . Accessed: June 2016

6. Adachi Y, et al. Lenvatinib in Combination with Everolimus
Demonstrated Enhanced Antiangiogenesis and Antitumor Activity in
Human RCC Xenograft Models. AACR 2016; #3264

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

8. SPC Afinitor. Available at: http://www.ema.europa.eu/docs/en_GB
/document_library/EPAR_-_Product_Information/human/001038/WC500022814
.pdf Accessed: June 2016

9. National Cancer Institute at the National Institute of Health.
Available
at:http://www.cancer.gov/types/kidney/patient/kidney-treatment-pdq

10. National Cancer Institute at the National Institute of Health.
Available at: http://www.cancer.gov/types/kidneyLast accessed: June
2016

Date of preparation: July 2016

Job code: Lenvatinib-UK0068

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

Contact:
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: Alex Davies/Callum
Haire
+44(0)7716 324 722 / +44(0)7867 429 637
Alex.Davies@toniclc.com
Callum.Haire@toniclc.com