WHITEHOUSE STATION, N.J.,
Sept. 4, 2014 /PRNewswire/
-- 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.
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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 that was symptomatic, was rapidly progressive,
required urgent intervention, occurred with a decline in
performance status, or was confirmed at 4 to 6 weeks with repeat
imaging. 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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SOURCE Merck