Opinion for KEYTRUDA Based on Efficacy and
Safety Data in More than 1,500 Patients with Advanced Melanoma as
Both First-Line Therapy and in those Previously Treated
Merck (NYSE:MRK), known as MSD outside the United States and
Canada, today announced that the Committee for Medicinal Products
for Human Use (CHMP) of the European Medicines Agency (EMA) has
adopted a positive opinion recommending approval of KEYTRUDA®
(pembrolizumab), the company’s anti-PD-1 therapy, for the treatment
of advanced (unresectable or metastatic) melanoma, as both
first-line therapy and in previously treated patients. The CHMP
positive opinion for KEYTRUDA, which is based on data in more than
1,500 adult patients with advanced melanoma, will now be reviewed
by the European Commission for central marketing authorization in
the European Union (EU).
“Merck is committed to bringing KEYTRUDA to people with advanced
melanoma in Europe as rapidly as possible, and the positive CHMP
opinion marks a significant step forward,” said Roger Dansey,
therapeutic area head and senior vice president, oncology late
stage development, Merck Research Laboratories. “We have
established a broad data set for KEYTRUDA in the treatment of
advanced melanoma, and have demonstrated improvements in
progression free survival compared to chemotherapy and a survival
benefit compared to ipilimumab. We look forward to working with
European health authorities to make KEYTRUDA available to
patients.”
Pembrolizumab, which will be marketed under the worldwide brand
name of KEYTRUDA, is one of the first of a new generation of
immunotherapies that works by blocking the PD-1 pathway. KEYTRUDA
was the first anti-PD-1 therapy approved in the United States and
the first medicine to be accepted under the UK’s Early Access to
Medicines Scheme (EAMS), which was introduced to help patients
benefit from promising, innovative treatments before a European
license has been granted.
Data Supporting the CHMP Positive Opinion
The positive opinion was based on data from more than 1,500
patients with advanced melanoma treated with KEYTRUDA as
monotherapy in three studies – from a large Phase 1b study,
KEYNOTE-001; from a randomized, controlled study KEYNOTE-002; and
an interim analysis from a second, randomized, controlled study,
KEYNOTE-006. In KEYNOTE-001, the largest Phase 1b study to date of
an anti-PD-1 antibody, KEYTRUDA demonstrated durable objective
responses in patients with advanced melanoma. KEYNOTE-002, a Phase
2 study, showed KEYTRUDA was superior to chemotherapy for
progression-free survival in ipilimumab refractory advanced
melanoma. KEYNOTE-006, a Phase 3 study, showed KEYTRUDA was
superior to ipilimumab for overall survival, progression-free
survival, and overall response rate. The trial was stopped early in
March 2015 based on the recommendation of the study’s independent
Data Monitoring Committee as it had met its two primary endpoints.
The CHMP recommended approval of KEYTRUDA monotherapy at a dose of
2 mg/kg every three weeks, which is the currently approved dose for
advanced melanoma in the U.S.
About Melanoma
Melanoma, the most serious form of skin cancer, is characterized
by the uncontrolled growth of pigment-producing cells. The
incidence of melanoma has been increasing over the past four
decades. In 2012, approximately 232,130 new cases were diagnosed
worldwide, and the incidence in Europe was estimated to be 100,300.
The five-year survival rates for advanced or metastatic melanoma
(Stage IV) are estimated to be 15 to 20 percent.
About KEYTRUDA® (pembrolizumab)
KEYTRUDA (pembrolizumab) is a humanized monoclonal antibody that
blocks the interaction between PD-1 and its ligands, PD-L1 and
PD-L2. By binding to the PD-1 receptor and blocking the interaction
with the receptor ligands, KEYTRUDA releases the PD-1
pathway-mediated inhibition of the immune response, including the
anti-tumor immune response.
KEYTRUDA is indicated in the United States at a dose of 2 mg/kg
administered as an intravenous infusion over 30 minutes every three
weeks for the treatment of patients with unresectable or metastatic
melanoma and disease progression following ipilimumab and, if BRAF
V600 mutation positive, a BRAF inhibitor. This indication is
approved under accelerated approval based on tumor response rate
and durability of response. An improvement in survival or
disease-related symptoms has not yet been established. Continued
approval for this indication may be contingent upon verification
and description of clinical benefit in the confirmatory trials.
Merck is advancing a broad and fast-growing clinical development
program for KEYTRUDA with more than 85 clinical trials – across
more than 30 tumor types and over 14,000 patients – both as a
monotherapy and in combination with other therapies.
Selected Important Safety Information for KEYTRUDA
Pneumonitis occurred in 12 (2.9%) of 411 patients with advanced
melanoma receiving KEYTRUDA (the approved indication in the United
States), including Grade 2 or 3 cases in 8 (1.9%) and 1 (0.2%)
patients, respectively. 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 pneumonitis.
Colitis (including microscopic colitis) occurred in 4 (1%) of
411 patients, including Grade 2 or 3 cases in 1 (0.2%) and 2 (0.5%)
patients respectively, receiving KEYTRUDA. 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.
Hepatitis (including autoimmune hepatitis) occurred in 2 (0.5%)
of 411 patients, including a Grade 4 case in 1 (0.2%) patient,
receiving KEYTRUDA. 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.
Hypophysitis occurred in 2 (0.5%) of 411 patients, including a
Grade 2 case in 1 and a Grade 4 case in 1 (0.2% each) patient,
receiving KEYTRUDA. Monitor for signs and symptoms of hypophysitis.
Administer corticosteroids for Grade 2 or greater hypophysitis.
Withhold KEYTRUDA for Grade 2; withhold or discontinue for Grade 3;
and permanently discontinue KEYTRUDA for Grade 4 hypophysitis.
Nephritis occurred in 3 (0.7%) patients receiving KEYTRUDA,
consisting of one case of Grade 2 autoimmune nephritis (0.2%) and
two cases of interstitial nephritis with renal failure (0.5%), one
Grade 3 and one Grade 4. 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.
Hyperthyroidism occurred in 5 (1.2%) of 411 patients, including
Grade 2 or 3 cases in 2 (0.5%) and 1 (0.2%) patients respectively,
receiving KEYTRUDA. Hypothyroidism occurred in 34 (8.3%) of 411
patients, including a Grade 3 case in 1 (0.2%) patient, receiving
KEYTRUDA. Thyroid disorders can occur at any time during treatment.
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 corticosteroids for Grade 3 or greater
hyperthyroidism. Withhold KEYTRUDA for Grade 3; permanently
discontinue KEYTRUDA for Grade 4 hyperthyroidism. Isolated
hypothyroidism may be managed with replacement therapy without
treatment interruption and without corticosteroids.
Other clinically important immune-mediated adverse reactions can
occur. The following clinically significant, immune-mediated
adverse reactions occurred in less than 1% of patients treated with
KEYTRUDA: exfoliative dermatitis, uveitis, arthritis, myositis,
pancreatitis, hemolytic anemia, partial seizures arising in a
patient with inflammatory foci in brain parenchyma, adrenal
insufficiency, myasthenic syndrome, optic neuritis, and
rhabdomyolysis.
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 of the adverse
reaction to Grade 1 or less, initiate corticosteroid taper and
continue to taper over at least 1 month. Restart KEYTRUDA if the
adverse reaction remains at Grade 1 or less. Permanently
discontinue KEYTRUDA for any severe or Grade 3 immune-mediated
adverse reaction that recurs and for any life-threatening
immune-mediated adverse reaction.
Based on its mechanism of action, KEYTRUDA may 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.
For the treatment of advanced melanoma, KEYTRUDA was
discontinued for adverse reactions in 6% of 89 patients who
received the recommended dose of 2 mg/kg and 9% of 411 patients
across all doses studied. Serious adverse reactions occurred in 36%
of patients receiving KEYTRUDA. The most frequent serious adverse
drug reactions reported in 2% or more of patients were renal
failure, dyspnea, pneumonia, and cellulitis.
The most common adverse reactions (reported in ≥20% of patients)
were fatigue (47%), cough (30%), nausea (30%), pruritus (30%), rash
(29%), decreased appetite (26%), constipation (21%), arthralgia
(20%), and diarrhea (20%).
The recommended dose of KEYTRUDA is 2 mg/kg administered as an
intravenous infusion over 30 minutes every three weeks until
disease progression or unacceptable toxicity. No formal
pharmacokinetic drug interaction studies have been conducted with
KEYTRUDA. 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. Safety and
effectiveness of KEYTRUDA have not been established in pediatric
patients.
Our Focus on Cancer
Our goal is to translate breakthrough science into innovative
oncology medicines to help people with cancer worldwide. At Merck
Oncology, 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. For more information about
our oncology clinical trials, visit
www.merck.com/clinicaltrials.
About Merck
Today’s Merck is a global healthcare leader working to help the
world be well. Merck is known as MSD outside the United States and
Canada. 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 healthcare through far-reaching policies, programs and
partnerships. For more information, visit www.merck.com and connect
with us on Twitter, Facebook and YouTube.
Forward-Looking Statement
This news release includes “forward-looking statements” within
the meaning of the safe harbor provisions of the United States
Private Securities Litigation Reform Act of 1995. These statements
are based upon the current beliefs and expectations of Merck’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 healthcare
legislation in the United States and internationally; global trends
toward healthcare cost containment; technological advances, new
products and patents attained by competitors; challenges inherent
in new product development, including obtaining regulatory
approval; Merck’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 Merck’s patents and other
protections for innovative products; and the exposure to
litigation, including patent litigation, and/or regulatory
actions.
Merck 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 Merck’s 2014 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).
# # #
Please see Prescribing Information for KEYTRUDA (pembrolizumab)
at
http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf
and the Medication Guide for KEYTRUDA at
http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf
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MerckMedia:Pam Eisele, 267-305-3558Claire Mulhearn,
908-236-1118orInvestors:Joseph Romanelli, 908-740-1986Justin Holko,
908-740-1879
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