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September 5, 2018 5:45 am ET

First Approval for LENVIMA in China and First New Therapy for the First-line Treatment of Unresectable HCC Approved in China in a Decade

TOKYO & KENILWORTH, N.J.–(BUSINESS WIRE)–Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) and
Merck (NYSE: MRK), known as MSD outside of the United States and Canada,
announced today that the China National Medical Products Administration
(NMPA) approved the kinase inhibitor LENVIMA^® (lenvatinib) as
a single agent for the treatment of patients with unresectable
hepatocellular carcinoma (HCC) who have not received prior systemic
therapy. In China, the application of LENVIMA was submitted in October
2017 and was designated for Priority Review by the NMPA due to LENVIMA’s
significant clinical benefit compared to existing treatments, leading to
approval in approximately 10 months. This approval marks the first for
LENVIMA in China, where the incidence of HCC is high, and the first new
systemic therapy approved for the first-line treatment of unresectable
HCC in China in ten years.

“Over the past decade, there have been limited treatment options
available for patients with unresectable HCC,” said Dr. Takashi Owa,
Vice President and Chief Medicine Creation Officer, Oncology Business
Group, Eisai. “We are pleased to be able to deliver LENVIMA to HCC
patients in China, and we are thankful for the collaborative efforts by
regulatory and government authorities, as well as the patients and
physicians who participated in the clinical studies and made this
approval possible.”

“Today’s milestone for LENVIMA is an important one for patients in China
living with unresectable HCC, which is historically difficult to treat
and has a poor prognosis,” said Dr. Roy Baynes, senior vice president
and head of global clinical development, chief medical officer, Merck
Research Laboratories. “Merck remains committed to bringing new
treatment advances to patients in China. The approval of LENVIMA,
through our collaboration with Eisai, is the third cancer medicine in
our portfolio to be approved in China this year – reinforcing the great
progress being made to bring new treatment options forward for Chinese
patients.”

The approval was based on results from the REFLECT study (Study 304), an
open-label, Phase 3 trial where LENVIMA demonstrated a treatment effect
on overall survival (OS) by statistical confirmation of non-inferiority
when compared with the standard of care, sorafenib, in 954 patients with
previously untreated unresectable HCC; patients randomized to the
LENVIMA arm did not have a statistically significant improvement in OS
compared to those in the sorafenib arm. LENVIMA demonstrated
statistically significant superiority and clinically meaningful
improvements in progression-free survival (PFS), time to progression
(TTP) and objective response rate (ORR). In a subpopulation analysis of
288 patients in the study from the greater Chinese region (mainland
China, Hong Kong and Taiwan), LENVIMA demonstrated efficacy based on
non-inferiority of OS compared to sorafenib, with improvements also
observed in PFS, TTP and ORR. Approximately 80% of patients in the
subpopulation were living with HCC resulting from chronic hepatitis B
virus (HBV), which has high unmet medical need. For these patients,
LENVIMA demonstrated non-inferiority based on OS compared with
sorafenib, thereby demonstrating the effect of LENVIMA in patients with
HCC resulting from HBV.

In the China package insert, the five most common adverse reactions
observed in patients treated with LENVIMA were hypertension (45%),
fatigue (44%), diarrhea (39%), decreased appetite (34%) and decreased
weight (31%), which is consistent with the known side-effect profile of
LENVIMA.

Liver cancer is the second leading cause of cancer-related deaths and is
estimated to be responsible for approximately 750,000 deaths per year
globally. Additionally, approximately 780,000 cases are newly diagnosed
each year, about 80% of which occur in Asian regions. Specifically, in
China, there are approximately 395,000 new cases and 380,000 deaths per
year, accounting for approximately 50% of cases worldwide. HCC accounts
for 85% to 90% of primary liver cancer cases. Unresectable HCC, for
which treatment options are limited, is extremely difficult to treat,
and the development of new treatments is necessary.

Since the initial launch, more than 10,000 patients have been treated
with LENVIMA. Today, LENVIMA is approved as a treatment for refractory
thyroid cancer in over 50 countries including the United States, Japan,
in Europe and Asia, and as combination with everolimus as a second-line
treatment for renal cell carcinoma (RCC) in over 45 countries including
the United States and in Europe. For HCC, LENVIMA was approved for use
in Japan in March 2018, and in the United States and Europe in August
2018. In Japan, approximately 3,000 HCC patients have been treated with
LENVIMA since approval of this indication.

About the REFLECT Trial (Study 304)

REFLECT was a large (n=954) Phase 3, randomized, multicenter, open-label
trial conducted by Eisai to compare the efficacy and safety of LENVIMA
versus sorafenib as a first-line systemic treatment in patients with
unresectable HCC. Patients at 154 trial sites in 20 countries were
randomized to receive LENVIMA 12 mg or 8 mg once a day depending on body
weight (≥60 kg or <60 kg, respectively) (n=478) or sorafenib 400 mg
twice a day (n=476). Treatment was continued until disease progression
or unacceptable toxicity. The primary endpoint of this study was OS,
tested first for non-inferiority to sorafenib, then for superiority. The
key secondary efficacy endpoints of this study included PFS, TTP and
ORR, tested for superiority to sorafenib.

In the China package insert, REFLECT showed that LENVIMA achieved the
primary endpoint, demonstrating a treatment effect on OS by statistical
confirmation of non-inferiority to sorafenib. Patients treated with
LENVIMA experienced a median OS of 13.6 months compared to 12.3 months
with sorafenib (Hazard Ratio [HR]: 0.92; 95% Confidence Interval [CI]:
0.79-1.06). Patients randomized to the LENVIMA arm did not have a
statistically significant improvement in OS compared to those in the
sorafenib arm. In addition, LENVIMA showed statistically significant
superiority and clinically meaningful improvements in the secondary
efficacy endpoints of PFS, TTP and ORR, as confirmed by a blinded
independent imaging review:

• Median PFS was doubled with LENVIMA compared to sorafenib: 7.3 months
  versus 3.6 months (HR: 0.64; 95% CI: 0.55–0.75; p<0.00001) per blinded
  independent imaging review based on mRECIST criteria.
• Median TTP was doubled with LENVIMA compared to sorafenib: 7.4 months
  versus 3.7 months (HR: 0.60; 95% CI: 0.51–0.71; p<0.00001) per blinded
  independent imaging review based on mRECIST criteria.
• LENVIMA showed nearly 3.5 times the ORR of sorafenib: 40.6% (95% CI:
  36.2-45.0) versus 12.4% (95% CI: 9.4-15.4) per blinded independent
  imaging review based on mRECIST criteria (odds ratio 5.01; 95% CI:
  3.59-7.01; p<0.00001).

About the Subpopulation Analysis of Patients from the Greater
Chinese Region

The results of subpopulation analysis of patients from the greater
Chinese region were based on 288 patients out of the 954 HCC patients
who participated in the REFLECT study. In this subpopulation analysis,
median OS was 15.0 months for LENVIMA versus 10.2 months for sorafenib
(HR: 0.73; 95% CI: 0.55-0.96; nominal p=0.02620). Independent imaging
review based on mRECIST criteria revealed the following results: PFS
(LENVIMA 8.4 months versus sorafenib 3.6 months in median [HR: 0.47; 95%
CI: 0.35-0.64; nominal p<0.00001]), TTP (LENVIMA 9.2 months versus
sorafenib 3.6 months in median [HR: 0.45; 95% CI: 0.33-0.62; nominal
p<0.00001]) and ORR (LENVIMA 43.8% versus sorafenib 13.2% [odds ratio
5.14; 95% CI: 2.84-9.31; nominal p<0.00001]).

Additionally, of the 288 patients in the subpopulation, approximately
80% (n=242) were living with HCC resulting from HBV. An analysis of
these patients revealed the following results for OS: LENVIMA (n=123)
14.9 months versus sorafenib (n=119) 9.9 months in median (HR: 0.72; 95%
CI: 0.53-0.97).

About Unresectable Hepatocellular Carcinoma (HCC)

Liver cancer is the second leading cause of cancer-related deaths and is
estimated to be responsible for 750,000 deaths per year globally.
Additionally, 780,000 cases are newly diagnosed each year. There is a
large regional difference, with about 80% of new cases occurring in
Asian regions, including China and Japan. HCC accounts for 85% to 90% of
primary liver cancer cases. HCC is associated with chronic liver
disease, in particular cirrhosis. Major causes of cirrhosis include
hepatitis B virus and hepatitis C virus. However, according to a recent
investigation, non-B/non-C HCC is on the rise. Surgery is the first
option for treatment, but for patients with unresectable HCC who are not
amenable for potentially curative therapeutic interventions, which
include liver transplant, surgical resection and tumor ablation
(typically radiofrequency ablation or cryotherapy), or who are not
suitable for transarterial chemoembolization (TACE), treatment options
are limited and the prognosis is very poor.

About LENVIMA

^®

(lenvatinib) capsules 10 mg
and 4 mg

LENVIMA^® (lenvatinib) is a kinase inhibitor that is indicated
in the U.S.:

• For the treatment of patients with locally recurrent or metastatic,
  progressive radioactive iodine-refractory differentiated thyroid
  cancer (DTC)
• In combination with everolimus, for the treatment of patients with
  advanced renal cell carcinoma (RCC) following one prior
  anti-angiogenic therapy
• For the first-line treatment of patients with unresectable
  hepatocellular carcinoma (HCC)

LENVIMA, discovered and developed by Eisai, is a kinase inhibitor that
inhibits the kinase activities of vascular endothelial growth factor
(VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). LENVIMA
inhibits other kinases that have been implicated in pathogenic
angiogenesis, tumor growth, and cancer progression in addition to their
normal cellular functions, including fibroblast growth factor (FGF)
receptors FGFR1-4; the platelet derived growth factor receptor alpha
(PDGFRα), KIT, and RET. Lenvatinib also exhibited antiproliferative
activity in hepatocellular carcinoma cell lines dependent on activated
FGFR signaling with a concurrent inhibition of FGF-receptor substrate 2α
(FRS2α) phosphorylation.

Important Safety Information in the U.S.

Warnings and Precautions

Hypertension. In DTC, hypertension occurred in 73% of patients on
LENVIMA (44% grade 3-4). In RCC, hypertension occurred in 42% of
patients on LENVIMA + everolimus (13% grade 3). Systolic blood pressure
≥160 mmHg occurred in 29% of patients, and 21% had diastolic blood
pressure ≥100 mmHg. In HCC, hypertension occurred in 45% of
LENVIMA-treated patients (24% grade 3). Grade 4 hypertension was not
reported in HCC.

Serious complications of poorly controlled hypertension have been
reported. Control blood pressure prior to initiation. Monitor blood
pressure after 1 week, then every 2 weeks for the first 2 months, and
then at least monthly thereafter during treatment. Withhold and resume
at reduced dose when hypertension is controlled or permanently
discontinue based on severity.

Cardiac Dysfunction. Serious and fatal cardiac dysfunction can
occur with LENVIMA. Across clinical trials in 799 patients with DTC,
RCC, and HCC, grade 3 or higher cardiac dysfunction occurred in 3% of
LENVIMA-treated patients. Monitor for clinical symptoms or signs of
cardiac dysfunction. Withhold and resume at reduced dose upon recovery
or permanently discontinue based on severity.

Arterial Thromboembolic Events. Among patients receiving LENVIMA
or LENVIMA + everolimus, arterial thromboembolic events of any severity
occurred in 2% of patients in RCC and HCC and 5% in DTC. Grade 3-5
arterial thromboembolic events ranged from 2% to 3% across all clinical
trials.

Permanently discontinue following an arterial thrombotic event. The
safety of resuming after an arterial thromboembolic event has not been
established and LENVIMA has not been studied in patients who have had an
arterial thromboembolic event within the previous 6 months.

Hepatotoxicity. Across clinical studies enrolling 1,327
LENVIMA-treated patients with malignancies other than HCC, serious
hepatic adverse reactions occurred in 1.4% of patients. Fatal events,
including hepatic failure, acute hepatitis and hepatorenal syndrome,
occurred in 0.5% of patients. In HCC, hepatic encephalopathy occurred in
8% of LENVIMA-treated patients (5% grade 3-5). Grade 3-5 hepatic failure
occurred in 3% of LENVIMA-treated patients. 2% of patients discontinued
LENVIMA due to hepatic encephalopathy and 1% discontinued due to hepatic
failure.

Monitor liver function prior to initiation, then every 2 weeks for the
first 2 months, and at least monthly thereafter during treatment.
Monitor patients with HCC closely for signs of hepatic failure,
including hepatic encephalopathy. Withhold and resume at reduced dose
upon recovery or permanently discontinue based on severity.

Renal Failure or Impairment. Serious including fatal renal
failure or impairment can occur with LENVIMA. Renal impairment was
reported in 14% and 7% of LENVIMA-treated patients in DTC and HCC,
respectively. Grade 3-5 renal failure or impairment occurred in 3% of
patients with DTC and 2% of patients with HCC, including 1 fatal event
in each study. In RCC, renal impairment or renal failure was reported in
18% of LENVIMA + everolimus–treated patients (10% grade 3).

Initiate prompt management of diarrhea or dehydration/hypovolemia.
Withhold and resume at reduced dose upon recovery or permanently
discontinue for renal failure or impairment based on severity.

Proteinuria. In DTC and HCC, proteinuria was reported in 34% and
26% of LENVIMA-treated patients, respectively. Grade 3 proteinuria
occurred in 11% and 6% in DTC and HCC, respectively. In RCC, proteinuria
occurred in 31% of patients receiving LENVIMA + everolimus (8% grade 3).

Monitor for proteinuria prior to initiation and periodically during
treatment. If urine dipstick proteinuria ≥2+ is detected, obtain a
24-hour urine protein. Withhold and resume at reduced dose upon recovery
or permanently discontinue based on severity.

Diarrhea. Of the 737 LENVIMA-treated patients in DTC and HCC,
diarrhea occurred in 49% (6% grade 3). In RCC, diarrhea occurred in 81%
of LENVIMA + everolimus–treated patients (19% grade 3). Diarrhea was the
most frequent cause of dose interruption/reduction, and diarrhea
recurred despite dose reduction.

Promptly initiate management of diarrhea. Withhold and resume at reduced
dose upon recovery or permanently discontinue based on severity.

Fistula Formation and Gastrointestinal Perforation. Of the 799
patients treated with LENVIMA or LENVIMA + everolimus in DTC, RCC, and
HCC, fistula or gastrointestinal perforation occurred in 2%. Fistulas
and gastrointestinal perforations have also been reported in other
lenvatinib clinical trials and in post-marketing experience.
Pneumothorax has been reported with and without clear evidence of a
bronchopleural fistula. Some reports of gastrointestinal perforation,
fistula, and pneumothorax occurred in association with tumor regression
or necrosis. In most cases of fistula formation or gastrointestinal
perforation, risk factors such as prior surgery or radiotherapy were
present.

Permanently discontinue in patients who develop gastrointestinal
perforation of any severity or grade 3-4 fistula.

QT Interval Prolongation. In DTC, QT/QTc interval prolongation
occurred in 9% of LENVIMA-treated patients and QT interval prolongation
of >500 ms occurred in 2%. In RCC, QTc interval increases of >60 ms
occurred in 11% of patients receiving LENVIMA + everolimus and QTc
interval >500 ms occurred in 6%. In HCC, QTc interval increases of >60
ms occurred in 8% of LENVIMA-treated patients and QTc interval >500 ms
occurred in 2%.

Monitor and correct electrolyte abnormalities at baseline and
periodically during treatment. Monitor electrocardiograms in patients
with congenital long QT syndrome, congestive heart failure,
bradyarrhythmias, or those who are taking drugs known to prolong the QT
interval, including Class Ia and III antiarrhythmics. Withhold and
resume at reduced dose upon recovery based on severity.

Hypocalcemia. In DTC, grade 3-4 hypocalcemia occurred in 9% of
LENVIMA-treated patients. In 65% of cases, hypocalcemia improved or
resolved following calcium supplementation with or without dose
interruption or dose reduction. In RCC, grade 3-4 hypocalcemia occurred
in 6% of LENVIMA + everolimus–treated patients. In HCC, grade 3
hypocalcemia occurred in 0.8% of LENVIMA-treated patients.

Monitor blood calcium levels at least monthly and replace calcium as
necessary during treatment. Withhold and resume at reduced dose upon
recovery or permanently discontinue depending on severity.

Reversible Posterior Leukoencephalopathy Syndrome. Across
clinical studies of 1,823 patients who received LENVIMA as a single
agent, RPLS occurred in 0.3%. Confirm diagnosis of RPLS with MRI.
Withhold and resume at reduced dose upon recovery or permanently
discontinue depending on severity and persistence of neurologic symptoms.

Hemorrhagic Events. Serious including fatal hemorrhagic events
can occur with LENVIMA. In DTC, RCC, and HCC clinical trials,
hemorrhagic events, of any grade, occurred in 29% of the 799 patients
treated with LENVIMA as a single agent or in combination with
everolimus. The most frequently reported hemorrhagic events (all grades
and occurring in at least 5% of patients) were epistaxis and hematuria.
In DTC, grade 3-5 hemorrhage occurred in 2% of LENVIMA-treated patients,
including 1 fatal intracranial hemorrhage among 16 patients who received
LENVIMA and had CNS metastases at baseline. In RCC, grade 3-5 hemorrhage
occurred in 8% of LENVIMA + everolimus–treated patients, including 1
fatal cerebral hemorrhage. In HCC, grade 3-5 hemorrhage occurred in 5%
of LENVIMA-treated patients, including 7 fatal hemorrhagic events.

Serious tumor-related bleeds, including fatal hemorrhagic events,
occurred in LENVIMA-treated patients in clinical trials and in the
postmarketing setting. In postmarketing surveillance, serious and fatal
carotid artery hemorrhages were seen more frequently in patients with
anaplastic thyroid carcinoma (ATC) than other tumors. Safety and
effectiveness of LENVIMA in patients with ATC have not been demonstrated
in clinical trials.

Consider the risk of severe or fatal hemorrhage associated with tumor
invasion or infiltration of major blood vessels (eg, carotid artery).
Withhold and resume at reduced dose upon recovery or permanently
discontinue based on severity.

Impairment of Thyroid Stimulating Hormone Suppression/Thyroid
Dysfunction. LENVIMA impairs exogenous thyroid suppression. In DTC,
88% of patients had baseline thyroid stimulating hormone (TSH) level
≤0.5 mU/L. In patients with normal TSH at baseline, elevation of TSH
level >0.5 mU/L was observed post baseline in 57% of LENVIMA-treated
patients. In RCC and HCC, grade 1 or 2 hypothyroidism occurred in 24% of
LENVIMA + everolimus–treated patients and 21% of LENVIMA-treated
patients, respectively. In patients with normal or low TSH at baseline,
elevation of TSH was observed post baseline in 70% of LENVIMA-treated
patients in HCC and 60% of LENVIMA + everolimus–treated patients in RCC.

Monitor thyroid function prior to initiation and at least monthly during
treatment. Treat hypothyroidism according to standard medical practice.

Wound Healing Complications. Wound healing complications,
including fistula formation and wound dehiscence, can occur with
LENVIMA. Withhold for at least 6 days prior to scheduled surgery. Resume
after surgery based on clinical judgment of adequate wound healing.
Permanently discontinue in patients with wound healing complications.

Embryo-fetal Toxicity. Based on its mechanism of action and data
from animal reproduction studies, LENVIMA can cause fetal harm when
administered to pregnant women. In animal reproduction studies, oral
administration of lenvatinib during organogenesis at doses below the
recommended clinical doses resulted in embryotoxicity, fetotoxicity, and
teratogenicity in rats and rabbits. Advise pregnant women of the
potential risk to a fetus; and advise females of reproductive potential
to use effective contraception during treatment with LENVIMA and for at
least 30 days after the last dose.

Adverse Reactions

In DTC, the most common adverse reactions (≥30%) observed in
LENVIMA-treated patients were hypertension (73%), fatigue (67%),
diarrhea (67%), arthralgia/myalgia (62%), decreased appetite (54%),
decreased weight (51%), nausea (47%), stomatitis (41%), headache (38%),
vomiting (36%), proteinuria (34%), palmar-plantar erythrodysesthesia
syndrome (32%), abdominal pain (31%), and dysphonia (31%). The most
common serious adverse reactions (≥2%) were pneumonia (4%), hypertension
(3%), and dehydration (3%). Adverse reactions led to dose reductions in
68% of LENVIMA-treated patients; 18% discontinued LENVIMA. The most
common adverse reactions (≥10%) resulting in dose reductions were
hypertension (13%), proteinuria (11%), decreased appetite (10%), and
diarrhea (10%); the most common adverse reactions (≥1%) resulting in
discontinuation of LENVIMA were hypertension (1%) and asthenia (1%).

In RCC, the most common adverse reactions (≥30%) observed in LENVIMA +
everolimus–treated patients were diarrhea (81%), fatigue (73%),
arthralgia/myalgia (55%), decreased appetite (53%), vomiting (48%),
nausea (45%), stomatitis (44%), hypertension (42%), peripheral edema
(42%), cough (37%), abdominal pain (37%), dyspnea (35%), rash (35%),
decreased weight (34%), hemorrhagic events (32%), and proteinuria (31%).
The most common serious adverse reactions (≥5%) were renal failure
(11%), dehydration (10%), anemia (6%), thrombocytopenia (5%), diarrhea
(5%), vomiting (5%), and dyspnea (5%). Adverse reactions led to dose
reductions or interruption in 89% of patients. The most common adverse
reactions (≥5%) resulting in dose reductions were diarrhea (21%),
fatigue (8%), thrombocytopenia (6%), vomiting (6%), nausea (5%), and
proteinuria (5%). Treatment discontinuation due to an adverse reaction
occurred in 29% of patients.In HCC, the most common adverse reactions
(≥20%) observed in LENVIMA-treated patients were hypertension (45%),
fatigue (44%), diarrhea (39%), decreased appetite (34%),
arthralgia/myalgia (31%), decreased weight (31%), abdominal pain (30%),
palmar-plantar erythrodysesthesia syndrome (27%), proteinuria (26%),
dysphonia (24%), hemorrhagic events (23%), hypothyroidism (21%), and
nausea (20%). The most common serious adverse reactions (≥2%) were
hepatic encephalopathy (5%), hepatic failure (3%), ascites (3%), and
decreased appetite (2%). Adverse reactions led to dose reductions or
interruption in 62% of patients. The most common adverse reactions (≥5%)
resulting in dose reductions were fatigue (9%), decreased appetite (8%),
diarrhea (8%), proteinuria (7%), hypertension (6%), and palmar-plantar
erythrodysesthesia syndrome (5%). Treatment discontinuation due to an
adverse reaction occurred in 20% of patients. The most common adverse
reactions (≥1%) resulting in discontinuation of LENVIMA were fatigue
(1%), hepatic encephalopathy (2%), hyperbilirubinemia (1%), and hepatic
failure (1%).

Use in Specific Populations

Because of the potential for serious adverse reactions in breastfed
infants, advise women to discontinue breastfeeding during treatment and
for at least 1 week after last dose. LENVIMA may impair fertility in
males and females of reproductive potential.

No dose adjustment is recommended for patients with mild (CLcr 60-89
mL/min) or moderate (CLcr 30-59 mL/min) renal impairment. LENVIMA
concentrations may increase in patients with DTC or RCC and severe (CLcr
15-29 mL/min) renal impairment. Reduce the dose for patients with RCC or
DTC and severe renal impairment. There is no recommended dose for
patients with HCC and severe renal impairment. LENVIMA has not been
studied in patients with end stage renal disease.

No dose adjustment is recommended for patients with HCC and mild hepatic
impairment (Child-Pugh A). There is no recommended dose for patients
with HCC with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic
impairment.

No dose adjustment is recommended for patients with DTC or RCC and mild
or moderate hepatic impairment. LENVIMA concentrations may increase in
patients with DTC or RCC and severe hepatic impairment. Reduce the dose
for patients with DTC or RCC and severe hepatic impairment.

For more information about LENVIMA please see available full Prescribing
Information.

About the Eisai and Merck Strategic Collaboration

In March 2018, Eisai and Merck, through an affiliate, entered into a
strategic collaboration for the worldwide co-development and
co-commercialization of LENVIMA. Under the agreement, the companies will
jointly develop and commercialize LENVIMA, both as monotherapy and in
combination with Merck’s anti-PD-1 therapy KEYTRUDA^®
(pembrolizumab). In addition to ongoing clinical studies of the
combination, the companies will jointly initiate new clinical studies
evaluating the LENVIMA and KEYTRUDA combination to support 11 potential
indications in six types of cancer, as well as a basket trial targeting
six additional cancer types. The LENVIMA and KEYTRUDA combination is not
approved in any cancer types today.

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 philosophy. With approximately 10,000 employees working
across our global network of R&D facilities, manufacturing sites and
marketing subsidiaries, we strive to realize our human health
care philosophy by delivering innovative products in various
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 www.eisai.com.

Merck’s Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology
medicines to help people with cancer worldwide. At Merck, the potential
to bring new hope to people with cancer drives our purpose and
supporting accessibility to our cancer medicines is our commitment.

As part of our focus on cancer, Merck is committed to exploring the
potential of immuno-oncology with one of the largest development
programs in the industry across more than 30 tumor types. We also
continue to strengthen our portfolio through strategic acquisitions and
are prioritizing the development of several promising oncology
candidates with the potential to improve the treatment of advanced
cancers.

For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

About Merck

For more than a century, Merck, a leading global biopharmaceutical
company known as MSD outside of the United States and Canada, has been
inventing for life, bringing forward medicines and vaccines for many of
the world’s most challenging diseases. Through our prescription
medicines, vaccines, biologic therapies and animal health products, we
work with customers and operate in more than 140 countries to deliver
innovative health solutions. We also demonstrate our commitment to
increasing access to health care through far-reaching policies, programs
and partnerships. Today, Merck continues to be at the forefront of
research to advance the prevention and treatment of diseases that
threaten people and communities around the world – including cancer,
cardio-metabolic diseases, emerging animal diseases, Alzheimer’s disease
and infectious diseases including HIV and Ebola.

For more information, visit www.merck.com and connect
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Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., USA

This news release of Merck & Co., Inc., Kenilworth, N.J., USA (the
“company”) includes “forward-looking statements” within the meaning of
the safe harbor provisions of the U.S. Private Securities Litigation
Reform Act of 1995. These statements are based upon the current beliefs
and expectations of the company’s management and are subject to
significant risks and uncertainties. There can be no guarantees with
respect to pipeline products that the products will receive the
necessary regulatory approvals or that they will prove to be
commercially successful. If underlying assumptions prove inaccurate or
risks or uncertainties materialize, actual results may differ materially
from those set forth in the forward-looking statements.

Risks and uncertainties include but are not limited to, general industry
conditions and competition; general economic factors, including interest
rate and currency exchange rate fluctuations; the impact of
pharmaceutical industry regulation and health care legislation in the
United States and internationally; global trends toward health care cost
containment; technological advances, new products and patents attained
by competitors; challenges inherent in new product development,
including obtaining regulatory approval; the company’s ability to
accurately predict future market conditions; manufacturing difficulties
or delays; financial instability of international economies and
sovereign risk; dependence on the effectiveness of the company’s patents
and other protections for innovative products; and the exposure to
litigation, including patent litigation, and/or regulatory actions.

The company undertakes no obligation to publicly update any
forward-looking statement, whether as a result of new information,
future events or otherwise. Additional factors that could cause results
to differ materially from those described in the forward-looking
statements can be found in the company’s 2017 Annual Report on Form 10-K
and the company’s other filings with the Securities and Exchange
Commission (SEC) available at the SEC’s Internet site (www.sec.gov).

KEYTRUDA^® is a registered trademark of Merck Sharp & Dohme
Corp., a subsidiary of Merck & Co., Inc., Kenilworth, N.J., U.S.A.

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