Merck (NYSE:MRK), known as MSD outside the United States and
Canada, today announced that the U.S. Food and Drug Administration
(FDA) has approved KEYTRUDA® (pembrolizumab) at a dose of 2 mg/kg
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.
KEYTRUDA is the first anti-PD-1 (programmed death receptor-1)
therapy approved in the United States and received FDA’s
Breakthrough Therapy designation for advanced melanoma, which was
granted based on the significance of early study findings and the
unmet medical need. For the recommended 2 mg/kg dose based on data
in 89 patients, the overall response rate was 24 percent (95% CI:
15, 34), with one complete response and 20 partial responses
(21/89). At the time of analysis, 86 percent (18/21) of patients
with objective responses had ongoing responses with durations
ranging from 1.4+ to 8.5+ months, including eight patients with
ongoing responses of 6 months or longer. Fourteen percent (3/21)
had progression of disease 2.8, 2.9, and 8.2 months after initial
response.
KEYTRUDA is a humanized monoclonal antibody that works by
increasing the ability of the body’s immune system to fight
advanced melanoma. KEYTRUDA blocks the interaction between PD-1 and
its ligands, PD-L1 and PD-L2, and may affect both tumor cells and
healthy cells. Immune-mediated adverse reactions occurred with
KEYTRUDA including pneumonitis, colitis, hepatitis, hypophysitis,
nephritis, hyperthyroidism, and hypothyroidism. Based on the
severity of the adverse reaction, KEYTRUDA should be withheld or
discontinued and corticosteroids administered. Based on its
mechanism of action, KEYTRUDA may cause fetal harm when
administered to a pregnant woman. Female patients of reproductive
potential should be advised of the potential hazard to a fetus. For
more information regarding immune-mediated adverse reactions and
use in pregnancy, see “Selected Important Safety Information”
below.
“KEYTRUDA embodies Merck’s unwavering commitment to pursue
breakthrough science to help people who are facing the most
challenging diseases,” said Kenneth C. Frazier, chairman and chief
executive officer, Merck. “We are grateful to the people with
advanced melanoma who participated in our trials, and the
scientific and medical community for the shared effort that has led
to the accelerated approval of KEYTRUDA.”
“The accelerated FDA approval of KEYTRUDA is a meaningful
development for patients with advanced melanoma,” said Dr. Omid
Hamid, Director of the Melanoma Center at The Angeles Clinic and
Research Institute, and a principal investigator for the
pembrolizumab melanoma clinical program. “Our new ability to target
the PD-1 pathway with KEYTRUDA is a very exciting step in the
immunotherapy field.”
Merck is conducting ongoing Phase 2 and 3 clinical studies in
advanced melanoma, which are designed to provide further
confirmatory evidence for KEYTRUDA in this indication. Merck plans
to make KEYTRUDA available within one week from today’s FDA
approval.
Study Cohort Supporting the Accelerated FDA Approval of
Single-Agent KEYTRUDA
The approval of KEYTRUDA was based on data from a multi-center,
open-label, randomized, dose-comparative study cohort of the
ongoing KEYNOTE-001 Phase 1b trial in patients with unresectable or
metastatic melanoma and progression of disease. Key eligibility
criteria included prior treatment with ipilimumab (two or more
doses at 3 mg/kg or higher) and a BRAF or MEK inhibitor, if BRAF
V600 mutation positive; and disease progression within 24 weeks
following the last dose of ipilimumab. Patients were randomized to
receive 2 mg/kg (n=89) or 10 mg/kg (n=84) of KEYTRUDA every 3 weeks
until unacceptable toxicity or disease progression. The major
efficacy outcome measures were confirmed overall response rate as
assessed by blinded independent central review using Response
Evaluation Criteria in Solid Tumors (RECIST 1.1) and duration of
response. Tumor response was assessed every 12 weeks.
Selected Important Safety Information for KEYTRUDA
Pneumonitis occurred in 12 (2.9%) of 411 patients, including
Grade 2 or 3 cases in 8 (1.9%) and 1 (0.2%) patients respectively,
receiving KEYTRUDA. 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.
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.
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 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.
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.
Commitment to Access for KEYTRUDA
Merck is committed to making KEYTRUDA accessible to patients.
Reimbursement support for eligible patients receiving KEYTRUDA,
including help with out-of-pocket costs and co-pay assistance, is
available through The Merck Access
Program. For eligible patients who are uninsured, financial
assistance is available through Merck’s patient assistance program.
More information is available by calling 1-855-257-3932 or visiting
www.merckaccessprogram-keytruda.com.
About KEYTRUDA
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.
Our Focus on Cancer
Our goal is to translate breakthrough science into biomedical
innovations to help people with cancer worldwide. For Merck
Oncology, helping people fight cancer is our passion, supporting
accessibility to our cancer medicines is our commitment, and
pursuing research in immuno-oncology is our focus 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 consumer care 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 2013 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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