Companies to Jointly Develop and
Commercialize LENVIMA, as Monotherapy and in Combination with
Merck’s KEYTRUDA® (pembrolizumab) for Multiple Cancer
Types
Eisai Books LENVIMA Product Sales and
Companies to Share Development and Marketing Costs Equally, as well
as Gross Profits From LENVIMA
LENVIMA/KEYTRUDA Combination Already Granted
U.S. FDA Breakthrough Therapy Designation for Renal Cell Carcinoma;
Expanded Joint Development Program to Support 11 Additional
Potential Indications Across Six Other Cancer Types
Merck’s Strong Commercial Footprint and
Medical Expertise, Combined with Eisai’s Extensive Real-World
Evidence for LENVIMA, Will Expedite Patient Access Worldwide for
Current and Future Potential Indications
Eisai Co., Ltd. and Merck (NYSE:MRK), known as MSD outside the
United States and Canada, today announced that the companies have
agreed upon a strategic collaboration for the worldwide
co-development and co-commercialization of LENVIMA® (lenvatinib
mesylate), an orally available tyrosine kinase inhibitor discovered
by Eisai. Under the agreement, Eisai and Merck will develop and
commercialize LENVIMA jointly, both as monotherapy and in
combination with Merck’s anti-PD-1 therapy, KEYTRUDA®
(pembrolizumab).
This press release features multimedia. View
the full release here:
http://www.businesswire.com/news/home/20180307006398/en/
Eisai will book LENVIMA product sales globally, as monotherapy
and in combination, and Merck and Eisai will share gross profits
equally. LENVIMA is currently approved as monotherapy for use in
the treatment of thyroid cancer, as well as in combination with
everolimus for the treatment of patients with renal cell carcinoma
(RCC) who have failed previous therapy. Applications for regulatory
approval of LENVIMA monotherapy for the treatment of hepatocellular
carcinoma have been submitted in Japan, the United States, Europe,
China and other countries.
A Phase 3 study (Study 307), sponsored by Eisai, is ongoing to
evaluate separate combinations of LENVIMA with KEYTRUDA
(pembrolizumab) or LENVIMA with everolimus versus chemotherapy
alone for the treatment of RCC. In January 2018, the companies
announced that the U.S. Food and Drug Administration (FDA) granted
Breakthrough Therapy Designation for the LENVIMA/KEYTRUDA
combination in advanced and/or metastatic RCC. This was based on
interim results from an ongoing Phase 1b/2 trial (Study
111/KEYNOTE-146), evaluating the combination in select solid tumors
(including RCC and endometrial cancer), which provided evidence for
synergistic effects on the observed overall response rate,
regardless of treatment experience or PD-L1 tumor expression.
Per the agreement, the companies will also jointly initiate new
clinical studies evaluating the LENVIMA/KEYTRUDA combination to
support 11 potential indications in six types of cancer
(endometrial cancer, non-small cell lung cancer, hepatocellular
carcinoma, head and neck cancer, bladder cancer and melanoma), as
well as a basket trial targeting multiple cancer types.
“Aiming to maximize the potential of LENVIMA and expedite the
creation of innovative treatments in this age of "Cancer
Evolution," we have entered into this collaboration with Merck who
developed the anti-PD-1 antibody KEYTRUDA,” commented Haruo Naito,
Representative Corporate Officer and CEO of Eisai Co., Ltd. “By
providing new treatment options including for refractory cancers
with no hopes for a cure to date, we are striving to further
contribute to increasing the benefits provided to patients and
their families.”
“Together with Eisai, we aim to maximize the value of LENVIMA
for its current indications while jointly pursuing additional
approvals in combination with KEYTRUDA across a wide range of
cancers,” said Dr. Roger M. Perlmutter, President, Merck Research
Laboratories. “There is strong scientific evidence supporting
synergistic effects of KEYTRUDA when used in combination with
LENVIMA, and the companies have already received Breakthrough
Therapy Designation from the U.S. FDA for the KEYTRUDA/LENVIMA
combination in renal cell carcinoma. Through this collaboration, we
will both broaden our oncology portfolio and have the opportunity
to help even more cancer patients around the world.”
Financial Considerations
Gross profits from LENVIMA product sales globally will be shared
equally by Eisai and Merck. Expenses incurred during
co-development, including for studies evaluating LENVIMA as
monotherapy, will be shared equally by the two companies.
Under the agreement, Merck will pay Eisai an upfront payment of
$300 million U.S. dollars and up to $650 million U.S. dollars for
certain option rights through 2020 (Eisai’s financial year: fiscal
year ended March 2021), as well as $450 million U.S. dollars as
reimbursement for research and development expenses. In addition,
Eisai is eligible to receive up to $385 million U.S. dollars
associated with the achievement of certain clinical and regulatory
milestones and a maximum of up to $3.97 billion U.S. dollars for
the achievement of milestones associated with sales of LENVIMA.
Assuming the achievement of all development and commercial goals
for all indications, the total amount of upfront, option and
regulatory and sales milestone payments has the potential to reach
up to $5.76 billion U.S. dollars.
The impact of this collaboration on Eisai's consolidated
financial results has been incorporated into the Notification
Regarding Revision of Consolidated Financial Results Forecasts
(IFRS) for the Fiscal Year Ending March 31, 2018 announced on March
8 (Japan).
About the Phase 1b/2 Study (Study 111/KEYNOTE-146) that
Supported Breakthrough Therapy Designation for the LENVIMA/KEYTRUDA
Combination
Study 111/KEYNOTE-146 is a multicenter, open-label, Phase 1b/2
clinical study being carried out in the United States and the
European Union to evaluate the efficacy and safety of LENVIMA in
combination with KEYTRUDA (pembrolizumab). The primary objective of
the Phase 1b portion of the study was to determine the maximum
tolerated dose in patients with unresectable solid tumors
(endometrial cancer, melanoma, non-small cell lung cancer, RCC,
squamous cell carcinoma of the head and neck, and urothelial
cancer) who had progressed after treatment with approved therapies
or for which there are no standard effective therapies available.
The initial part of Phase 2 enrolled patients with select solid
tumors after previous treatment with 0-2 lines of systemic therapy
(unless discussed with the sponsor) with a recommended dosage based
on the results of the Phase 1b part. The primary endpoint of the
initial part of Phase 2 was objective response rate (ORR) after 24
weeks of treatment, with select secondary endpoints including ORR,
disease control rate, progression-free survival, and duration of
response. The expansion part of Phase 2 is ongoing, and enrollment
of patients is continuing in the endometrial cancer cohort.
From the results of the analysis (investigator review) of the
RCC cohort 1 (n=30) in Study 111/KEYNOTE-146 as of March 1, 2017,
the primary endpoint of the Phase 2 portion, ORR after 24 weeks of
treatment (ORR Week 24) was 63 percent (95% CI, 44-80), with tumor
regression observed in 93 percent (28/30) of patients since the
initiation of treatment (baseline). A tumor response was observed
regardless of previous treatment experience or tumor PD-L1
expression. In this cohort, the most frequently observed adverse
events (top six) were diarrhea, fatigue, hypothyroidism,
stomatitis, hypertension, and nausea.
The results of the interim analysis (n=23) of the endometrial
cancer cohort in Study 111/KEYNOTE-146 as of December 1, 2016,
indicated ORR Week 24 of 52.2 percent (95% CI, 30.6-73.2) based on
independent radiologic review and 47.8 percent (95% CI, 26.8-69.4)
based on investigator review. Additionally, tumor regression was
observed regardless of the state of microsatellite instability
(MSI). Anti-PD-1 antibodies are generally less effective in
patients with low frequency of MSI, which is a biomarker for the
inability to repair errors in the base sequence of DNA, or who are
MSI negative. In this cohort, the most frequently observed adverse
events (top five) were hypertension, fatigue, arthralgia, diarrhea,
and nausea.
Meanwhile, a similar Phase 1b clinical study (Study
115/KEYNOTE-523) in Japanese patients with unresectable solid
tumors and a Phase 1b clinical study (Study 116/KEYNOTE-524) of the
combination therapy in hepatocellular carcinoma in Japan and the
United States are both underway.
About LENVIMA® (lenvatinib mesylate)
Discovered and developed in-house by Eisai, LENVIMA is an orally
administered multiple receptor tyrosine kinase (RTK) inhibitor with
a novel binding mode that selectively inhibits the kinase
activities of vascular endothelial growth factor (VEGF) receptors
(VEGFR1, VEGFR2 and VEGFR3) and fibroblast growth factor (FGF)
receptors (FGFR1, FGFR2, FGFR3 and FGFR4) in addition to other
pathway-related RTKs (including the platelet-derived growth factor
(PDGF) receptor PDGFRα; KIT; and RET) involved in tumor
angiogenesis, tumor progression and modification of tumor
immunity.
Currently, Eisai has obtained approval for LENVIMA as a
treatment for refractory thyroid cancer in over 50 countries,
including the United States, Japan, in Europe and Asia.
Additionally, Eisai has obtained approval for the agent in
combination with everolimus as a second-line treatment for RCC in
over 40 countries, including the United States and in Europe. In
Europe, the agent was launched under the brand name Kisplyx® for
RCC.
Furthermore, Eisai has submitted applications for an indication
covering hepatocellular carcinoma in Japan (June 2017), the United
States and Europe (July 2017), China (October 2017), Taiwan
(December 2017) and other countries.
The eight major clinical studies in progress on LENVIMA are as
follows:
- A Phase 3 clinical study (Study 307) of
separate combinations of LENVIMA with KEYTRUDA (pembrolizumab) or
LENVIMA with everolimus versus chemotherapy alone in RCC
(first-line) conducted in Japan, the United States and Europe.
- A Phase 3 clinical study (Study 308) of
LENVIMA in thyroid cancer being conducted in China.
- A Phase 2 clinical study (Study 215) of
LENVIMA in biliary tract cancer being conducted in Japan.
- A Phase 2 clinical study (Study 209) of
LENVIMA in non-small cell lung cancer with RET translocations being
conducted in Japan, the United States, Europe and Asia.
- A Phase 1b/2 clinical study (Study
111/KEYNOTE-146) of LENVIMA in combination with KEYTRUDA in select
solid tumors (RCC, endometrial cancer, non-small cell lung cancer,
urothelial cancer, squamous cell carcinoma of the head and neck,
and melanoma) being conducted in the United States and European
Union. Based on interim results, the combination treatment has been
granted Breakthrough Therapy Designation by the U.S. FDA for the
potential treatment of patients with advanced and/or metastatic
RCC.
- A Phase 1b clinical study (Study
115/KEYNOTE-523) of LENVIMA in combination with KEYTRUDA in select
solid tumors (RCC, endometrial cancer, non-small cell lung cancer,
urothelial cancer, squamous cell carcinoma of the head and neck,
and melanoma) being conducted in Japan.
- A Phase 1b clinical study (Study
116/KEYNOTE-524) of LENVIMA in combination with KEYTRUDA in
hepatocellular carcinoma being conducted in Japan and the United
States.
- A Phase 1b clinical study of LENVIMA in
combination with nivolumab in hepatocellular carcinoma being
conducted in Japan.
LENVIMA® (lenvatinib) Indications in the
U.S.
LENVIMA® (lenvatinib) is a kinase inhibitor that is indicated
for:
- Differentiated Thyroid Cancer (DTC):
single agent for patients with locally recurrent or metastatic,
progressive, radioactive iodine-refractory DTC.
- Renal Cell Cancer (RCC): in combination
with everolimus for patients with advanced RCC following one prior
anti-angiogenic therapy.
Important Safety Information
Warnings and Precautions
- In DTC, hypertension was reported in
73% of patients on LENVIMA (lenvatinib) vs 16% with placebo (44% vs
4% grade ≥3). In RCC, hypertension was reported in 42% of patients
on LENVIMA + everolimus vs 10% with everolimus alone (13% vs 2%
grade 3). Serious complications of poorly controlled hypertension,
including aortic dissection, have been reported. Systolic blood
pressure ≥160 mmHg occurred in 29% of patients, and 21% of patients
had a diastolic blood pressure ≥100 mmHg in the LENVIMA +
everolimus–treated group. Blood pressure should be controlled prior
to treatment and monitored throughout. Withhold dose for grade 3
hypertension despite optimal antihypertensive therapy; resume at
reduced dose when controlled at grade ≤2. Discontinue for
life-threatening hypertension
- In DTC, cardiac dysfunction was
reported in 7% of patients on LENVIMA vs 2% with placebo (2% vs 0%
grade ≥3). In RCC, decreased ejection fraction and cardiac failure
were reported in 10% of patients on LENVIMA + everolimus vs 6% with
everolimus alone (3% vs 2% grade 3). Monitor for signs/symptoms of
cardiac decompensation. Withhold LENVIMA for development of grade 3
cardiac dysfunction until improvement to grade 0, 1, or baseline.
Resume at reduced dose or discontinue based on severity and
persistence of cardiac dysfunction. Discontinue for grade 4 cardiac
dysfunction
- In DTC, arterial thromboembolic events
were reported in 5% of patients on LENVIMA vs 2% with placebo (3%
vs 1% grade ≥3). In RCC, arterial thromboembolic events were
reported in 2% of patients on LENVIMA + everolimus vs 6% with
everolimus alone (2% vs 4% grade ≥3). Discontinue following an
arterial thrombotic event. The safety of resuming LENVIMA 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
- Across clinical studies in which 1,160
patients received LENVIMA monotherapy, hepatic failure (including
fatal events) was reported in 3 patients and acute hepatitis in 1
patient. In DTC, ALT and AST increases (grade ≥3) occurred in 4%
and 5% of patients on LENVIMA, respectively, vs 0% with placebo. In
RCC, ALT and AST increases (grade ≥3) occurred in 3% of patients on
LENVIMA + everolimus vs 2% and 0% with everolimus alone,
respectively. Monitor liver function before initiation, then every
2 weeks for the first 2 months, and at least monthly thereafter
during treatment. Withhold dose for liver impairment grade ≥3 until
resolved to grade 0, 1, or baseline. Resume at reduced dose or
discontinue based on severity/persistence of hepatotoxicity.
Discontinue for hepatic failure
- In DTC, proteinuria was reported in 34%
of patients on LENVIMA vs 3% with placebo (11% vs 0% grade 3). In
RCC, proteinuria was reported in 31% of patients on LENVIMA +
everolimus vs 14% with everolimus alone (8% vs 2% grade 3). Monitor
for proteinuria before and during treatment. Withhold dose for
proteinuria ≥2 g/24 h. Resume at reduced dose when proteinuria
is <2 g/24 h. Discontinue for nephrotic syndrome
- In RCC, diarrhea was reported in 81% of
patients on LENVIMA + everolimus vs 34% with everolimus alone (19%
vs 2% grade ≥3). Initiate prompt medical management for the
development of diarrhea. Monitor for dehydration. Withhold dose for
diarrhea grade ≥3. Resume at a reduced dose when diarrhea resolves
to grade 1 or baseline. Permanently discontinue LENVIMA for grade 4
diarrhea despite medical management
- In DTC, events of renal impairment were
reported in 14% of patients on LENVIMA vs 2% with placebo (3% vs 1%
grade ≥3). In RCC, events of renal impairment were reported in 18%
of patients on LENVIMA + everolimus vs 12% with everolimus alone
(10% vs 2% grade ≥3). Withhold LENVIMA for grade 3 or 4 renal
failure/impairment. Resume at reduced dose or discontinue,
depending on severity/persistence of renal impairment. Active
management of diarrhea and any other gastrointestinal (GI) symptoms
should be initiated for grade 1 events
- In DTC, events of GI perforation or
fistula were reported in 2% of patients on LENVIMA vs 0.8% with
placebo. In RCC, events of GI perforation, abscess, or fistula
(grade ≥3) were reported in 2% of patients on LENVIMA (lenvatinib)
+ everolimus vs 0% with everolimus alone. Discontinue in patients
who develop GI perforation or life-threatening fistula
- In DTC, QT/QTc interval prolongation
was reported in 9% of patients on LENVIMA vs 2% with placebo (2% vs
0% >500 ms). In RCC, QTc interval increases >60 ms were
reported in 11% of patients on LENVIMA + everolimus (6% >500 ms)
vs 0% with everolimus alone. Monitor electrocardiograms in patients
with congenital long QT syndrome, congestive heart failure,
bradyarrhythmias, or patients taking drugs known to prolong the QT
interval. Monitor and correct electrolyte abnormalities in all
patients. Withhold dose for QTc interval prolongation >500 ms.
Resume at reduced dose when QTc prolongation resolves to
baseline
- In DTC, hypocalcemia (grade ≥3) was
reported in 9% of patients on LENVIMA vs 2% with placebo. In RCC,
hypocalcemia (grade ≥3) was reported in 6% of patients on LENVIMA +
everolimus vs 2% with everolimus alone. Monitor blood calcium
levels at least monthly and replace calcium as necessary. Interrupt
and adjust LENVIMA as necessary
- Across clinical studies in which 1,160
patients received LENVIMA monotherapy, reversible posterior
leukoencephalopathy syndrome (RPLS) was reported in 4 patients.
Withhold LENVIMA for RPLS until fully resolved. Resume at reduced
dose or discontinue based on the severity and persistence of
neurologic symptoms
- Across clinical studies in which 1,160
patients received LENVIMA monotherapy, hemorrhage (grade ≥3) was
reported in 2% of patients. In DTC, hemorrhagic events occurred in
35% of patients on LENVIMA vs 18% with placebo (2% vs 3% grade ≥3).
There was 1 fatal intracranial hemorrhage case among 16 patients
who received LENVIMA and had central nervous system metastases at
baseline. The most frequently reported hemorrhagic event was
epistaxis (11% grade 1, 1% grade 2). Discontinuation due to
hemorrhagic events occurred in 1% of patients on LENVIMA. In RCC,
hemorrhagic events occurred in 34% of patients on LENVIMA +
everolimus vs 26% with everolimus alone (8% vs 2% grade ≥3). The
most frequently reported hemorrhagic event was epistaxis (23% for
LENVIMA + everolimus vs 24% with everolimus alone). There was 1
fatal cerebral hemorrhage case. Discontinuation due to hemorrhagic
events occurred in 3% of patients on LENVIMA + everolimus. Consider
the risk of severe or fatal hemorrhage associated with tumor
invasion/infiltration of major blood vessels (eg, carotid artery).
Withhold LENVIMA for the development of grade 3 hemorrhage until
resolved to grade 0 or 1. Resume at reduced dose or discontinue
based on severity/persistence of hemorrhage. Discontinue for grade
4 hemorrhage
- In DTC patients with normal baseline
thyroid-stimulating hormone (TSH), elevation of TSH level above 0.5
mU/L was observed postbaseline in 57% of patients on LENVIMA vs 14%
with placebo. In RCC, grade 1 or 2 hypothyroidism occurred in 24%
of patients on LENVIMA + everolimus vs 2% with everolimus alone. In
RCC patients with normal or low TSH at baseline, elevation of TSH
was observed postbaseline in 60% of patients on LENVIMA +
everolimus vs 3% with everolimus alone. Monitor thyroid function
before initiation of and at least monthly throughout treatment.
Treat hypothyroidism according to standard medical practice to
maintain a euthyroid state
- Impaired wound healing, including
fistula formation, has been reported in patients receiving LENVIMA.
Temporary interruption of LENVIMA therapy should be considered in
patients undergoing major surgical procedures
- LENVIMA can cause fetal harm when
administered to a pregnant woman. Advise females of reproductive
potential to use effective contraception during treatment with
LENVIMA and for at least 2 weeks following completion of
therapy
Adverse Reactions
- In DTC, the most common adverse
reactions (≥30%) observed in LENVIMA-treated patients vs
placebo-treated patients were hypertension (73% vs 16%), fatigue
(67% vs 35%), diarrhea (67% vs 17%), arthralgia/myalgia (62% vs
28%), decreased appetite (54% vs 18%), weight decrease (51% vs
15%), nausea (47% vs 25%), stomatitis (41% vs 8%), headache (38% vs
11%), vomiting (36% vs 15%), proteinuria (34% vs 3%),
palmar-plantar erythrodysesthesia syndrome (32% vs 1%), abdominal
pain (31% vs 11%), and dysphonia (31% vs 5%)
- In DTC, adverse reactions led to dose
reductions in 68% of patients receiving LENVIMA (lenvatinib) and in
5% of patients receiving placebo; 18% of patients discontinued
LENVIMA and 5% discontinued placebo for adverse reactions. The most
common adverse reactions (≥10%) resulting in dose reductions of
LENVIMA 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 patients treated with LENVIMA +
everolimus vs everolimus alone were diarrhea (81% vs 34%), fatigue
(73% vs 40%), arthralgia/myalgia (55% vs 32%), decreased appetite
(53% vs 18%), vomiting (48% vs 12%), nausea (45% vs 16%),
stomatitis/oral inflammation (44% vs 50%), hypertension/increased
blood pressure (42% vs 10%), peripheral edema (42% vs 20%), cough
(37% vs 30%), abdominal pain (37% vs 8%), dyspnea/exertional
dyspnea (35% vs 28%), rash (35% vs 40%), weight decreased (34% vs
8%), hemorrhagic events (32% vs 26%), and proteinuria/urine protein
present (31% vs 14%). The most common serious adverse reactions
(≥5%) were renal failure (11%), dehydration (10%), anemia (6%),
thrombocytopenia (5%), diarrhea (5%), vomiting (5%), and dyspnea
(5%)
- In RCC, adverse reactions led to dose
reductions or interruption in 89% of patients receiving
LENVIMA + everolimus and in 54% of patients receiving
everolimus alone. The most common adverse reactions (≥5%) resulting
in dose reductions in the LENVIMA + everolimus–treated
group 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 the LENVIMA + everolimus–treated group and in
12% of patients in the everolimus-treated group
Use in Specific Populations
- Because of the potential for serious
adverse reactions in nursing infants, advise women to discontinue
breastfeeding during treatment
- LENVIMA may result in reduced fertility
in females of reproductive potential and may result in damage to
male reproductive tissues, leading to reduced fertility of unknown
duration
For more information about LENVIMA, click here for the full
Prescribing Information.
About KEYTRUDA® (pembrolizumab) Injection
100mg
KEYTRUDA is an anti-PD-1 therapy that works by increasing the
ability of the body’s immune system to help detect and fight tumor
cells. KEYTRUDA is a humanized monoclonal antibody that blocks the
interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby
activating T lymphocytes which may affect both tumor cells and
healthy cells.
KEYTRUDA (pembrolizumab) Indications and Dosing in the
U.S.
Melanoma
KEYTRUDA is indicated for the treatment of patients with
unresectable or metastatic melanoma at a fixed dose of 200 mg every
three weeks until disease progression or unacceptable toxicity.
Lung Cancer
KEYTRUDA, as a single agent, is indicated for the first-line
treatment of patients with metastatic non-small cell lung cancer
(NSCLC) whose tumors have high PD-L1 expression [tumor proportion
score (TPS) ≥50%] as determined by an FDA-approved test, with no
EGFR or ALK genomic tumor aberrations.
KEYTRUDA (pembrolizumab), as a single agent, is also indicated
for the treatment of patients with metastatic NSCLC whose tumors
express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with
disease progression on or after platinum-containing chemotherapy.
Patients with EGFR or ALK genomic tumor aberrations should have
disease progression on FDA-approved therapy for these aberrations
prior to receiving KEYTRUDA.
KEYTRUDA, in combination with pemetrexed and carboplatin, is
indicated for the first-line treatment of patients with metastatic
nonsquamous NSCLC. This indication is approved under accelerated
approval based on tumor response rate and progression-free
survival. Continued approval for this indication may be contingent
upon verification and description of clinical benefit in the
confirmatory trials.
In metastatic NSCLC, KEYTRUDA is administered at a fixed dose of
200 mg every three weeks until disease progression, unacceptable
toxicity, or up to 24 months in patients without disease
progression.
When administering KEYTRUDA (pembrolizumab) in combination with
chemotherapy, KEYTRUDA should be administered prior to chemotherapy
when given on the same day. See also the Prescribing Information
for pemetrexed and carboplatin.
Head and Neck Cancer
KEYTRUDA is indicated for the treatment of patients with
recurrent or metastatic head and neck squamous cell carcinoma
(HNSCC) with disease progression on or after platinum-containing
chemotherapy. This indication is approved under accelerated
approval based on tumor response rate and durability of response.
Continued approval for this indication may be contingent upon
verification and description of clinical benefit in the
confirmatory trials. In HNSCC, KEYTRUDA is administered at a fixed
dose of 200 mg every three weeks until disease progression,
unacceptable toxicity, or up to 24 months in patients without
disease progression.
Classical Hodgkin Lymphoma
KEYTRUDA is indicated for the treatment of adult and pediatric
patients with refractory classical Hodgkin lymphoma (cHL), or who
have relapsed after three or more prior lines of therapy. This
indication is approved under accelerated approval based on tumor
response rate and durability of response. Continued approval for
this indication may be contingent upon verification and description
of clinical benefit in the confirmatory trials. In adults with cHL,
KEYTRUDA (pembrolizumab) is administered at a fixed dose of 200 mg
every three weeks until disease progression or unacceptable
toxicity, or up to 24 months in patients without disease
progression. In pediatric patients with cHL, KEYTRUDA
(pembrolizumab) is administered at a dose of 2 mg/kg (up to a
maximum of 200 mg) every three weeks until disease progression or
unacceptable toxicity, or up to 24 months in patients without
disease progression.
Urothelial Carcinoma
KEYTRUDA is indicated for the treatment of patients with locally
advanced or metastatic urothelial carcinoma who are not eligible
for cisplatin-containing chemotherapy. This indication is approved
under accelerated approval based on tumor response rate and
duration of response. Continued approval for this indication may be
contingent upon verification and description of clinical benefit in
the confirmatory trials.
KEYTRUDA is also indicated for the treatment of patients with
locally advanced or metastatic urothelial carcinoma who have
disease progression during or following platinum-containing
chemotherapy or within 12 months of neoadjuvant or adjuvant
treatment with platinum-containing chemotherapy.
In locally advanced or metastatic urothelial carcinoma, KEYTRUDA
is administered at a fixed dose of 200 mg every three weeks until
disease progression or unacceptable toxicity, or up to 24 months in
patients without disease progression.
Microsatellite Instability-High (MSI-H) Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric
patients with unresectable or metastatic microsatellite
instability-high (MSI-H) or mismatch repair deficient (dMMR)
- solid tumors that have progressed
following prior treatment and who have no satisfactory alternative
treatment options, or
- colorectal cancer that has progressed
following treatment with fluoropyrimidine, oxaliplatin, and
irinotecan.
This indication is approved under accelerated approval based on
tumor response rate and durability of response. Continued approval
for this indication may be contingent upon verification and
description of clinical benefit in the confirmatory trials. The
safety and effectiveness of KEYTRUDA in pediatric patients with
MSI-H central nervous system cancers have not been established.
In adult patients with MSI-H cancer, KEYTRUDA is administered at
a fixed dose of 200 mg every three weeks until disease progression,
unacceptable toxicity, or up to 24 months in patients without
disease progression. In children with MSI-H cancer, KEYTRUDA
(pembrolizumab) is administered at a dose of 2 mg/kg (up to a
maximum of 200 mg) every three weeks until disease progression or
unacceptable toxicity, or up to 24 months in patients without
disease progression.
Gastric Cancer
KEYTRUDA is indicated for the treatment of patients with
recurrent locally advanced or metastatic gastric or
gastroesophageal junction (GEJ) adenocarcinoma whose tumors express
PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an
FDA-approved test, with disease progression on or after two or more
prior lines of therapy including fluoropyrimidine- and
platinum-containing chemotherapy and if appropriate,
HER2/neu-targeted therapy. This indication is approved under
accelerated approval based on tumor response rate and durability of
response. Continued approval for this indication may be contingent
upon verification and description of clinical benefit in the
confirmatory trials. The recommended dose of KEYTRUDA is 200 mg
every three weeks until disease progression, unacceptable toxicity,
or up to 24 months in patients without disease progression.
Selected Important Safety Information for
KEYTRUDA® (pembrolizumab)
KEYTRUDA can cause immune-mediated pneumonitis, including fatal
cases. Pneumonitis occurred in 94 (3.4%) of 2799 patients receiving
KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%),
and 5 (0.1%) pneumonitis, and occurred more frequently in patients
with a history of prior thoracic radiation (6.9%) compared to those
without (2.9%). Monitor patients for signs and symptoms of
pneumonitis. Evaluate suspected pneumonitis with radiographic
imaging. Administer corticosteroids for Grade 2 or greater
pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue
KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.
KEYTRUDA can cause immune-mediated colitis. Colitis occurred in
48 (1.7%) of 2799 patients receiving KEYTRUDA, including Grade 2
(0.4%), 3 (1.1%), and 4 (<0.1%) colitis. Monitor patients for
signs and symptoms of colitis. Administer corticosteroids for Grade
2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3;
permanently discontinue KEYTRUDA for Grade 4 colitis.
KEYTRUDA (pembrolizumab) can cause immune-mediated hepatitis.
Hepatitis occurred in 19 (0.7%) of 2799 patients receiving
KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%)
hepatitis. Monitor patients for changes in liver function.
Administer corticosteroids for Grade 2 or greater hepatitis and,
based on severity of liver enzyme elevations, withhold or
discontinue KEYTRUDA.
KEYTRUDA can cause hypophysitis. Hypophysitis occurred in 17
(0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2
(0.2%), 3 (0.3%), and 4 (<0.1%) hypophysitis. Monitor patients
for signs and symptoms of hypophysitis (including hypopituitarism
and adrenal insufficiency). Administer corticosteroids and hormone
replacement as clinically indicated. Withhold KEYTRUDA for Grade 2;
withhold or discontinue for Grade 3 or 4 hypophysitis.
KEYTRUDA can cause thyroid disorders, including hyperthyroidism,
hypothyroidism, and thyroiditis. Hyperthyroidism occurred in 96
(3.4%) of 2799 patients receiving KEYTRUDA, including Grade 2
(0.8%) and 3 (0.1%) hyperthyroidism. Hypothyroidism occurred in 237
(8.5%) of 2799 patients receiving KEYTRUDA, including Grade 2
(6.2%) and 3 (0.1%) hypothyroidism. The incidence of new or
worsening hypothyroidism was higher in patients with HNSCC,
occurring in 28 (15%) of 192 patients with HNSCC, including Grade 3
(0.5%) hypothyroidism. Thyroiditis occurred in 16 (0.6%) of 2799
patients receiving KEYTRUDA, including Grade 2 (0.3%) thyroiditis.
Monitor patients for changes in thyroid function (at the start of
treatment, periodically during treatment, and as indicated based on
clinical evaluation) and for clinical signs and symptoms of thyroid
disorders. Administer replacement hormones for hypothyroidism and
manage hyperthyroidism with thionamides and beta-blockers as
appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4
hyperthyroidism.
KEYTRUDA can cause type 1 diabetes mellitus, including diabetic
ketoacidosis, which have been reported in 6 (0.2%) of 2799
patients. Monitor patients for hyperglycemia or other signs and
symptoms of diabetes. Administer insulin for type 1 diabetes, and
withhold
KEYTRUDA (pembrolizumab) and administer antihyperglycemics in
patients with severe hyperglycemia.
KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred
in 9 (0.3%) of 2799 patients receiving KEYTRUDA, including Grade 2
(0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Monitor patients for
changes in renal function. Administer corticosteroids for Grade 2
or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently
discontinue KEYTRUDA for Grade 3 or 4 nephritis.
Immune-mediated rashes, including Stevens-Johnson syndrome
(SJS), toxic epidermal necrolysis (TEN) (some cases with fatal
outcome), exfoliative dermatitis, and bullous pemphigoid, can
occur. Monitor patients for suspected severe skin reactions and
based on the severity of the adverse reaction, withhold or
permanently discontinue KEYTRUDA (pembrolizumab) and administer
corticosteroids. For signs or symptoms of SJS or TEN, withhold
KEYTRUDA and refer the patient for specialized care for assessment
and treatment. If SJS or TEN is confirmed, permanently discontinue
KEYTRUDA.
KEYTRUDA can cause other clinically important immune-mediated
adverse reactions. These immune-mediated reactions may occur in any
organ system. For suspected immune-mediated adverse reactions,
ensure adequate evaluation to confirm etiology or exclude other
causes. Based on the severity of the adverse reaction, withhold
KEYTRUDA and administer corticosteroids. Upon improvement to Grade
1 or less, initiate corticosteroid taper and continue to taper over
at least 1 month. Based on limited data from clinical studies in
patients whose immune-related adverse reactions could not be
controlled with corticosteroid use, administration of other
systemic immunosuppressants can be considered. Resume KEYTRUDA when
the adverse reaction remains at Grade 1 or less following
corticosteroid taper. Permanently discontinue KEYTRUDA for any
Grade 3 immune-mediated adverse reaction that recurs and for any
life-threatening immune-mediated adverse reaction.
The following clinically significant immune-mediated adverse
reactions occurred in less than 1% (unless otherwise indicated) of
2799 patients: arthritis (1.5%), uveitis, myositis, Guillain-Barré
syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic
anemia, and partial seizures arising in a patient with inflammatory
foci in brain parenchyma. In addition, myelitis and myocarditis
were reported in other clinical trials, including classical Hodgkin
lymphoma, and postmarketing use.
Solid organ transplant rejection has been reported in
postmarketing use of KEYTRUDA. Treatment with KEYTRUDA may increase
the risk of rejection in solid organ transplant recipients.
Consider the benefit of treatment with KEYTRUDA vs the risk of
possible organ rejection in these patients.
KEYTRUDA can cause severe or life-threatening infusion-related
reactions, including hypersensitivity and anaphylaxis, which have
been reported in 6 (0.2%) of 2799 patients. Monitor patients for
signs and symptoms of infusion-related reactions, including rigors,
chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia,
and fever. For Grade 3 or 4 reactions, stop infusion and
permanently discontinue KEYTRUDA.
Immune-mediated complications, including fatal events, occurred
in patients who underwent allogeneic hematopoietic stem cell
transplantation (HSCT) after being treated with KEYTRUDA. Of 23
patients with cHL who proceeded to allogeneic HSCT after treatment
with KEYTRUDA (pembrolizumab) on any trial, 6 patients (26%)
developed graft-versus-host disease (GVHD), one of which was fatal,
and 2 patients (9%) developed severe hepatic veno-occlusive disease
(VOD) after reduced-intensity conditioning, one of which was fatal.
Cases of fatal hyperacute GVHD after allogeneic HSCT have also been
reported in patients with lymphoma who received a PD-1
receptor–blocking antibody before transplantation.
These complications may occur despite intervening therapy
between PD-1 blockade and allogeneic HSCT. Follow patients closely
for early evidence of transplant-related complications such as
hyperacute GVHD, severe (Grade 3 to 4) acute GVHD,
steroid-requiring febrile syndrome, hepatic VOD, and other
immune-mediated adverse reactions, and intervene promptly.
In clinical trials in patients with multiple myeloma, the
addition of KEYTRUDA to a thalidomide analogue plus dexamethasone
resulted in increased mortality. Treatment of these patients with a
PD-1 or PD-L1 blocking antibody in this combination is not
recommended outside of controlled clinical trials.
Based on its mechanism of action, KEYTRUDA can cause fetal harm
when administered to a pregnant woman. If used during pregnancy, or
if the patient becomes pregnant during treatment, apprise the
patient of the potential hazard to a fetus. Advise females of
reproductive potential to use highly effective contraception during
treatment and for 4 months after the last dose of KEYTRUDA.
In KEYNOTE-006, KEYTRUDA was discontinued due to adverse
reactions in 9% of 555 patients with advanced melanoma; adverse
reactions leading to discontinuation in more than one patient were
colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction
(0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). Adverse
reactions leading to interruption of KEYTRUDA occurred in 21% of
patients; the most common (≥1%) was diarrhea (2.5%). The most
common adverse reactions with KEYTRUDA vs ipilimumab were fatigue
(28% vs 28%), diarrhea (26% with KEYTRUDA), rash (24% vs 23%), and
nausea (21% with KEYTRUDA). Corresponding incidence rates are
listed for ipilimumab only for those adverse reactions that
occurred at the same or lower rate than with KEYTRUDA.
In KEYNOTE-010, KEYTRUDA monotherapy was discontinued due to
adverse reactions in 8% of 682 patients with metastatic NSCLC. The
most common adverse event resulting in permanent discontinuation of
KEYTRUDA was pneumonitis (1.8%). Adverse reactions leading to
interruption of KEYTRUDA occurred in 23% of patients; the most
common (≥1%) were diarrhea (1%), fatigue (1.3%), pneumonia (1%),
liver enzyme elevation (1.2%), decreased appetite (1.3%), and
pneumonitis (1%). The most common adverse reactions (occurring in
at least 20% of patients and at a higher incidence than with
docetaxel) were decreased appetite (25% vs 23%), dyspnea (23% vs
20%), and nausea (20% vs 18%).
In KEYNOTE-021(G1), when KEYTRUDA (pembrolizumab) was
administered in combination with carboplatin and pemetrexed
(carbo/pem) in advanced nonsquamous NSCLC, KEYTRUDA was
discontinued in 10% of 59 patients. The most common adverse
reaction resulting in discontinuation of KEYTRUDA (≥2%) was acute
kidney injury (3.4%). Adverse reactions leading to interruption of
KEYTRUDA occurred in 39% of patients; the most common (≥2%) were
fatigue (8%), neutrophil count decreased (8%), anemia (5%), dyspnea
(3.4%), and pneumonitis (3.4%). The most common adverse reactions
(≥20%) with KEYTRUDA compared to carbo/pem alone were fatigue (71%
vs 50%), nausea (68% vs 56%), constipation (51% vs 37%), rash (42%
vs 21%), vomiting (39% vs 27%), dyspnea (39% vs 21%), diarrhea (37%
vs 23%), decreased appetite (31% vs 23%), headache (31% vs 16%),
cough (24% vs 18%), dizziness (24% vs 16%), insomnia (24% vs 15%),
pruritus (24% vs 4.8%), peripheral edema (22% vs 18%), dysgeusia
(20% vs 11%), alopecia (20% vs 3.2%), upper respiratory tract
infection (20% vs 3.2%), and arthralgia (15% vs 24%). This study
was not designed to demonstrate a statistically significant
difference in adverse reaction rates for KEYTRUDA as compared to
carbo/pem alone for any specified adverse reaction.
In KEYNOTE-012, KEYTRUDA was discontinued due to adverse
reactions in 17% of 192 patients with HNSCC. Serious adverse
reactions occurred in 45% of patients. The most frequent serious
adverse reactions reported in at least 2% of patients were
pneumonia, dyspnea, confusional state, vomiting, pleural effusion,
and respiratory failure. The most common adverse reactions
(reported in at least 20% of patients) were fatigue, decreased
appetite, and dyspnea. Adverse reactions occurring in patients with
HNSCC were generally similar to those occurring in patients with
melanoma or NSCLC, with the exception of increased incidences of
facial edema (10% all Grades; 2.1% Grades 3 or 4) and new or
worsening hypothyroidism.
In KEYNOTE-087, KEYTRUDA was discontinued due to adverse
reactions in 5% of 210 patients with cHL, and treatment was
interrupted due to adverse reactions in 26% of patients. Fifteen
percent (15%) of patients had an adverse reaction requiring
systemic corticosteroid therapy. Serious adverse reactions occurred
in 16% of patients. The most frequent serious adverse reactions
(≥1%) included pneumonia, pneumonitis, pyrexia, dyspnea, GVHD, and
herpes zoster. Two patients died from causes other than disease
progression; one from GVHD after subsequent allogeneic HSCT and one
from septic shock. The most common adverse reactions (occurring in
≥20% of patients) were fatigue (26%), pyrexia (24%), cough (24%),
musculoskeletal pain (21%), diarrhea (20%), and rash (20%).
In KEYNOTE-052, KEYTRUDA (pembrolizumab) was discontinued due to
adverse reactions in 11% of 370 patients with locally advanced or
metastatic urothelial carcinoma. The most common adverse reactions
(in ≥20% of patients) were fatigue (38%), musculoskeletal pain
(24%), decreased appetite (22%), constipation (21%), rash (21%),
and diarrhea (20%). Eighteen patients (5%) died from causes other
than disease progression. Five patients (1.4%) who were treated
with KEYTRUDA experienced sepsis which led to death, and 3 patients
(0.8%) experienced pneumonia which led to death. Adverse reactions
leading to interruption of KEYTRUDA occurred in 22% of patients;
the most common (≥1%) were liver enzyme increase, diarrhea, urinary
tract infection, acute kidney injury, fatigue, joint pain, and
pneumonia. Serious adverse reactions occurred in 42% of patients,
the most frequent (≥2%) of which were urinary tract infection,
hematuria, acute kidney injury, pneumonia, and urosepsis.
In KEYNOTE-045, KEYTRUDA was discontinued due to adverse
reactions in 8% of 266 patients with locally advanced or metastatic
urothelial carcinoma. The most common adverse reaction resulting in
permanent discontinuation of KEYTRUDA was pneumonitis (1.9%).
Adverse reactions leading to interruption of KEYTRUDA occurred in
20% of patients; the most common (≥1%) were urinary tract infection
(1.5%), diarrhea (1.5%), and colitis (1.1%). The most common
adverse reactions (≥20%) in patients who received KEYTRUDA vs those
who received chemotherapy were fatigue (38% vs 56%),
musculoskeletal pain (32% vs 27%), pruritus (23% vs 6%), decreased
appetite (21% vs 21%), nausea (21% vs 29%), and rash (20% vs 13%).
Serious adverse reactions occurred in 39% of KEYTRUDA-treated
patients, the most frequent (≥2%) of which were urinary tract
infection, pneumonia, anemia, and pneumonitis.
It is not known whether KEYTRUDA is excreted in human milk.
Because many drugs are excreted in human milk, instruct women to
discontinue nursing during treatment with KEYTRUDA and for 4 months
after the final dose.
There is limited experience in pediatric patients. In a study,
40 pediatric patients (16 children aged 2 years to younger than 12
years and 24 adolescents aged 12 years to 18 years) with advanced
melanoma, lymphoma, or PD-L1–positive advanced, relapsed, or
refractory solid tumors were administered KEYTRUDA 2 mg/kg every 3
weeks. Patients received KEYTRUDA for a median of 3 doses (range
1–17 doses), with 34 patients (85%) receiving KEYTRUDA for 2 doses
or more. The safety profile in these pediatric patients was similar
to that seen in adults treated with KEYTRUDA. Toxicities that
occurred at a higher rate (≥15% difference) in these patients when
compared to adults under 65 years of age were fatigue (45%),
vomiting (38%), abdominal pain (28%), hypertransaminasemia (28%),
and hyponatremia (18%).
Please see Prescribing Information for KEYTRUDA
(pembrolizumab) at
http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf
and Patient Information/Medication Guide for KEYTRUDA at
http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf
Eisai’s Focus on Cancer
Eisai regards oncology as a key therapeutic area and is aiming
to discover revolutionary new medicines with the potential to cure
cancer by leveraging drug creation base technologies cultivated
through the discovery of Lenvima and Halaven, as well as
technologies associated with organic synthetic chemistry and drug
discovery science. Eisai’s research groups in Japan and the United
States are working on drug discovery activities using drug
discovery platforms mainly for the cancer microenvironment, driver
gene mutation and aberrant splicing in cancer cells, that are
Eisai’s strengths.
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 approximately 10,000 employees working across our global
network of R&D facilities, manufacturing sites and marketing
subsidiaries, we strive to realize our hhc 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,
helping people fight cancer is our passion and supporting
accessibility to our cancer medicines is our commitment. Our focus
is on pursuing research in immuno-oncology and we are accelerating
every step in the journey – from lab to clinic – to potentially
bring new hope to people with cancer.
As part of our focus on cancer, Merck is committed to exploring
the potential of immuno-oncology with one of the fastest-growing
development programs in the industry. We are currently executing an
expansive research program evaluating our anti-PD-1 therapy across
more than 30 tumor types. We also continue to strengthen our
immuno-oncology portfolio through strategic acquisitions and are
prioritizing the development of several promising immunotherapeutic
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 with us
on Twitter, Facebook, Instagram, YouTube
and LinkedIn.
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).
View source
version on businesswire.com: http://www.businesswire.com/news/home/20180307006398/en/
Eisai Public Relations
Department+81-(0)3-3817-5120orEisai Investor
Relations+81-(0)3-3817-3016orMerck RelationsPamela
Eisele, 267-305-3558orAnn Bush, 908-740-6677orMerck Investor
RelationsTeri Loxam, 908-740-1986orPeter Dannenbaum,
908-740-1037
Merck (NYSE:MRK)
Historical Stock Chart
From Mar 2024 to Apr 2024
Merck (NYSE:MRK)
Historical Stock Chart
From Apr 2023 to Apr 2024