FDA Accepts Supplemental Biologics License Application (sBLA) for KEYTRUDA® (pembrolizumab), Merck’s Anti-PD-1 Therapy, for First-Line Treatment of Advanced Melanoma, and Grants Priority Review


August 18, 2015 7:00 am ET

Merck Provides Additional Update: FDA Extends Action Date for Additional sBLA in Ipilimumab-Refractory Advanced Melanoma

KENILWORTH, N.J.–(BUSINESS WIRE)–Merck (NYSE:MRK), known as MSD outside the United States and Canada,
today announced the U.S. Food and Drug Administration (FDA) has accepted
for review a supplemental Biologics License Application (sBLA) for
KEYTRUDA® (pembrolizumab), Merck’s anti-PD-1 therapy. Merck
is seeking approval for KEYTRUDA, at the currently approved dose of 2
mg/kg every three weeks, for the first-line treatment of unresectable or
metastatic melanoma patients. The FDA granted Priority Review with a
PDUFA, or target action, date of December 19, 2015. Additionally, the
FDA has extended the action date for a separate sBLA for KEYTRUDA for
the treatment of patients with ipilimumab-refractory advanced melanoma.
The new action date is now December 24, 2015.

“Through our clinical program for KEYTRUDA we have accumulated
substantial data on the role of our anti-PD-1 therapy in advanced
melanoma. We look forward to the FDA’s review of each of these
applications, and to delivering on our goal of helping patients with
advanced melanoma to achieve long-term disease control and survival,”
said Dr. Roger M. Perlmutter, president, Merck Research Laboratories.

KEYTRUDA is currently 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.

The sBLA submission for first-line use in advanced melanoma was based in
part on data from KEYNOTE-006, a Phase 3 study which evaluated KEYTRUDA
in 834 patients with unresectable or metastatic melanoma with
progression of disease. Findings from this study were presented at the
2015 American Associated for Cancer Research (AACR) Annual Meeting and
published in the New England Journal of Medicinei.

Update on sBLA in Ipilimumab-Refractory Advanced Melanoma

The sBLA for ipilimumab-refractory advanced melanoma included data from
KEYNOTE-002. KEYNOTE-002 is the Phase 2 study which demonstrated
KEYTRUDA was superior to chemotherapy in helping more patients with
ipilimumab-refractory advanced melanoma achieve progression-free
survival (PFS). In an effort to provide the FDA with the most robust
data for KEYTRUDA in this population, Merck submitted an additional
analysis from KEYNOTE-002. The submission constitutes a major amendment
which will require additional time for review.

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.

Merck is advancing a broad and fast-growing clinical development program
for KEYTRUDA with more than 100 clinical trials – across more than 30
tumor types and enrolling more than 16,000 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, 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 (pembrolizumab). 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 (including
hypopituitarism and adrenal insufficiency). 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.

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

Type 1 diabetes mellitus, including diabetic ketoacidosis, has occurred
in patients receiving KEYTRUDA. Monitor patients for hyperglycemia and
other signs and symptoms of diabetes. Administer insulin for type 1
diabetes, and withhold KEYTRUDA in cases of severe hyperglycemia until
metabolic control is achieved.

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
(pembrolizumab) for Grade 2; permanently discontinue KEYTRUDA for Grade
3 or 4 nephritis.

Other clinically important immune-mediated adverse reactions can occur.
The following clinically significant, immune-mediated adverse reactions
occurred in patients treated with KEYTRUDA (pembrolizumab): exfoliative
dermatitis, uveitis, arthritis, myositis, pancreatitis, hemolytic
anemia, partial seizures arising in a patient with inflammatory foci in
brain parenchyma, severe dermatitis including bullous pemphigoid,
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.

Infusion-related reactions, including severe and life-threatening
reactions, have occurred in patients receiving KEYTRUDA. Monitor
patients for signs and symptoms of infusion-related reactions including
rigors, chills, wheezing, pruritus, flushing, rash, hypotension,
hypoxemia, and fever. For severe or life-threatening reactions, stop
infusion and permanently discontinue KEYTRUDA.

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 9% of 411 patients across all doses studied.
Adverse reactions, reported in at least two patients, that led to
discontinuations of KEYTRUDA were: pneumonitis, renal failure, and pain.
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

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 (pembrolizumab).
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.

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 – approximately
232,000 new cases were diagnosed worldwide in 2012. In the U.S.,
melanoma is one of the most common types of cancer diagnosed and is
responsible for the vast majority of skin cancer deaths. In 2015, an
estimated 73,870 people are expected to be diagnosed and an estimated
9,940 people are expected to die of the disease in the U.S. alone. The
five-year survival rates for advanced or metastatic melanoma (Stage IV)
are estimated to be 15 to 20 percent.

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 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,
and YouTube.

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 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


i Robert C, et al. Pembrolizumab versus
Ipilimumab in Advanced Melanoma. N Engl J Med 2015; 372:2521-2532

Pamela Eisele, 267-305-3558
Justin Holko, 908-740-1879
An Phan, 908-255-6325


Unsubscribe from email alerts