FDA Accepts Supplemental Biologics License
Application, Assigns Priority Review and Grants Breakthrough Therapy
Designation to Merck’s KEYTRUDA® (pembrolizumab) for First-Line
Treatment of Patients with Advanced Non-Small Cell Lung Cancer
Merck Has Also Submitted a Marketing Authorization
Application to the European Medicines Agency for KEYTRUDA in the Same Patient
Population
Submissions Based on Data from KEYNOTE-024 Trial
Showing Superior Progression-Free and Overall Survival Compared to Chemotherapy
in Patients Whose Tumors Express High Levels of PD-L1
KENILWORTH, N.J., Sept. 7, 2016 – Merck (NYSE: MRK),
known as MSD outside the United States and Canada, today announced that the
U.S. Food and Drug Administration (FDA) has accepted for Priority Review the
supplemental Biologics License Application (sBLA) for KEYTRUDA® (pembrolizumab),
the company’s anti-PD-1 therapy, for the first-line treatment of patients with
advanced non-small cell lung cancer (NSCLC) whose tumors express PD-L1, with a
PDUFA, or target action, date of Dec. 24, 2016. Additionally, the FDA
granted Breakthrough Therapy Designation for this indication. Merck has also
submitted a Marketing Authorization Application to the European Medicines
Agency for this indication.
The submissions were based on data from the pivotal phase
3 KEYNOTE-024 study, which showed that KEYTRUDA monotherapy resulted in
superior progression-free survival (PFS) as well as overall survival (OS)
compared with standard chemotherapy in patients with advanced NSCLC whose
tumors expressed high levels of PD-L1 (tumor proportion score of 50 percent or
more). Based on the results, the trial was stopped early to give patients still
on chemotherapy the opportunity to receive KEYTRUDA. Merck filed for approval
of KEYTRUDA in the first-line setting at a dose of 200 mg every three weeks,
the dose studied in KEYNOTE-024.
“Chemotherapy has been the foundation of first-line
treatment for non-small cell lung cancer for decades, so the significant
improvement in survival in patients with high PD-L1 expression seen with
KEYTRUDA compared to chemotherapy is welcome news,” said Dr. Roger M.
Perlmutter, president, Merck Research Laboratories. “We appreciate the
opportunity to work with regulatory authorities to make KEYTRUDA a first-line
treatment option in non-small cell lung cancer.”
The FDA’s Breakthrough Therapy Designation is intended
to expedite the availability of promising new therapies that are planned for
use, alone or in combination, to treat a serious or life-threatening disease or
condition when preliminary clinical evidence indicates substantial improvement
over existing therapies on one or more clinically significant endpoints. Merck
previously announced that KEYTRUDA (pembrolizumab) was granted breakthrough
status for specific patients with advanced melanoma, metastatic NSCLC in
previously treated patients, microsatellite instability high metastatic
colorectal cancer, and relapsed or refractory classical Hodgkin Lymphoma.
About KEYTRUDA® (pembrolizumab)
KEYTRUDA is a humanized monoclonal antibody that works
by increasing the ability of the body’s immune system to help detect and fight
tumor cells. KEYTRUDA 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 is administered as an intravenous infusion
over 30 minutes every three weeks for the approved indications. KEYTRUDA for
injection is supplied in a 100 mg single use vial.
KEYTRUDA Indications and Dosing
Melanoma
KEYTRUDA is indicated for the treatment of patients
with unresectable or metastatic melanoma at a dose of 2 mg/kg every three
weeks.
Lung Cancer
KEYTRUDA is indicated for the treatment of patients with metastatic non-small
cell lung cancer (NSCLC) whose tumors express PD-L1 as determined by an
FDA-approved test with disease progression on or after platinum-containing
chemotherapy, at a dose of 2 mg/kg every three weeks. Patients with EGFR or ALK
genomic tumor aberrations should have disease progression on FDA-approved
therapy for these aberrations prior to receiving KEYTRUDA (pembrolizumab). 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. An sBLA is currently under review with the FDA for full
approval of the existing second-line NSCLC indication. The application is based
on data from KEYNOTE-010, a pivotal phase 2/3 confirmatory trial which
demonstrated improved survival with KEYTRUDA compared to standard chemotherapy
in previously treated patients with advanced NSCLC who had PD-L1 expression on
one percent or more of the cancer cells. The FDA target action date is Oct. 24,
2016.
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 at a
fixed dose of 200 mg every three weeks. 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.
Selected Important Safety Information for KEYTRUDA® (pembrolizumab)
Immune-mediated pneumonitis occurred in 19 (3.5%) of
550 patients, including Grade 2 (1.1%), 3 (1.3%), 4 (0.4%), or 5 (0.2%)
pneumonitis and occurred more frequently in patients with a history of
asthma/chronic obstructive pulmonary disease (5.4%) or prior thoracic radiation
(6.0%). 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.
Immune-mediated colitis occurred in 4 (0.7%) of 550
patients, including Grade 2 (0.2%) or 3 (0.4%) 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.
Immune-mediated hepatitis occurred in patients
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 1 (0.2%) of 550 patients,
which was Grade 3 in severity. Monitor patients for signs and symptoms of
hypophysitis (including hypopituitarism and adrenal insufficiency). Administer
corticosteroids and hormone replacement as clinically indicated. Withhold
KEYTRUDA (pembrolizumab) for Grade 2; withhold or discontinue for Grade 3 or 4
hypophysitis.
Hyperthyroidism occurred in 10 (1.8%) of 550 patients,
including Grade 2 (0.7%) or 3 (0.3%) hyperthyroidism. Hypothyroidism occurred
in 38 (6.9%) of 550 patients, including Grade 2 (5.5%) or 3 (0.2%)
hypothyroidism. 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
replacement hormones for hypothyroidism and manage hyperthyroidism with
thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA
for Grade 3 or 4 hyperthyroidism.
Type 1 diabetes mellitus, including diabetic
ketoacidosis, occurred in 3 (0.1%) of 2117 patients. Monitor patients for
hyperglycemia or other signs and symptoms of diabetes. Administer insulin for
type 1 diabetes, and withhold KEYTRUDA and administer anti-hyperglycemics in
patients with severe hyperglycemia.
Immune-mediated nephritis occurred in patients receiving
KEYTRUDA. 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.
Other clinically important immune-mediated adverse
reactions can occur. 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% of 550 patients: rash, vasculitis,
hemolytic anemia, serum sickness, and myasthenia gravis.
Severe and life-threatening infusion-related reactions
have been reported in 3 (0.1%) of 2117 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 (pembrolizumab).
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.
KEYTRUDA was discontinued due to adverse reactions in
14% of 550 patients. Serious adverse reactions occurred in 38% of patients. The
most frequent serious adverse reactions reported in at least 2% of patients
were pleural effusion, pneumonia, dyspnea, pulmonary embolism and pneumonitis.
The most common adverse reactions (reported in at least 20% of patients) were
fatigue (44%), cough (29%), decreased appetite (25%), and dyspnea (23%).
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.
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.
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 that includes more than 330 clinical trials 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 125 years, Merck has been a global health care
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 health care through
far-reaching policies, programs and partnerships. For more information, visit www.merck.com and connect
with us on Twitter, Facebook, 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 2015 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
Patient Information/Medication Guide for KEYTRUDA at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf.
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