Merck Receives Breakthrough Therapy Designation from U.S. Food and Drug Administration for KEYTRUDA® (pembrolizumab) in Classical Hodgkin Lymphoma (cHL)
April 18, 2016 7:00 am ET
Fourth Designation for KEYTRUDA Follows Breakthrough Status in Advanced Melanoma, Non-Small Cell Lung Cancer, and Colorectal Cancer
KENILWORTH, N.J.–(BUSINESS WIRE)–Merck (NYSE:MRK), known as MSD outside the United States and Canada,
today announced that the U.S. Food and Drug Administration (FDA) has
granted Breakthrough Therapy Designation to KEYTRUDA® (pembrolizumab),
the company’s anti-PD-1 therapy, for the treatment of patients with
relapsed or refractory classical Hodgkin lymphoma (cHL). This is the
fourth Breakthrough Therapy Designation granted for KEYTRUDA.
“Merck has launched an ambitious clinical development program examining
the efficacy of KEYTRUDA in a broad range of solid and blood cancers,
and our studies of relapsed or refractory classical Hodgkin lymphoma are
quite promising,” said Dr. Roger M. Perlmutter, president, Merck
Research Laboratories. “The FDA’s Breakthrough Designation for this
blood cancer provides an important mechanism to assist us in bringing
this immunotherapy to patients who could benefit from its use.”
The FDA’s Breakthrough Therapy Designation is intended to expedite the
development and review of a candidate that is planned for use, alone or
in combination, to treat a serious or life-threatening disease or
condition when preliminary clinical evidence indicates that the drug may
demonstrate substantial improvement over existing therapies on one or
more clinically significant endpoints. KEYTRUDA was previously granted
breakthrough status for specific patients with advanced melanoma,
advanced non-small cell lung cancer (NSCLC), and advanced colorectal
The Breakthrough Therapy Designation in cHL is based on data from the
ongoing Phase 1b KEYNOTE-013 and Phase 2 KEYNOTE-087 studies evaluating
single agent KEYTRUDA in patients with cHL. Findings from the
KEYNOTE-013 study were presented at the 2015 American Society of
Hematology (ASH) Annual Meeting and data from KEYNOTE-087 will be
presented at an upcoming medical meeting.
The KEYTRUDA clinical development program includes patients with more
than 30 tumor types in more than 250 clinical trials, including more
than 100 trials that combine KEYTRUDA with other cancer treatments.
Registration-enabling trials of KEYTRUDA are currently enrolling
patients in melanoma, NSCLC, head and neck cancer, bladder cancer,
gastric cancer, colorectal cancer, esophageal cancer, breast cancer,
ovarian cancer, Hodgkin lymphoma, non-Hodgkin lymphoma, multiple
myeloma, and other tumors, with further trials in planning for other
About KEYTRUDA® (pembrolizumab) Injection
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 indicated for the treatment of patients with unresectable or
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. Patients with EGFR or ALK genomic
tumor aberrations should have disease progression on FDA-approved
therapy for these aberrations prior to receiving KEYTRUDA. 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 administered at a dose of 2 mg/kg as an intravenous infusion
over 30 minutes every three weeks for the approved indications.
About Hodgkin Lymphoma
Lymphoma is a type of blood cancer that affects the lymphatic system,
which removes excess fluids from the body and produces immune cells.
Lymphoma cells are abnormal lymphocytes which multiply and collect in
the lymph nodes and other tissues. Normal lymphocytes are a type of
white blood cell that fight infection. Hodgkin lymphoma (also called
Hodgkin disease) is a specific type of lymphoma and includes two
subtypes: classical Hodgkin lymphoma (cHL) and nodular lymphocyte
predominant Hodgkin lymphoma. In 2016, it is estimated that more than
8,500 people will be diagnosed with Hodgkin lymphoma in the U.S. alone
and cHL accounts for 95 percent of all Hodgkin lymphoma cases.
Selected Important Safety Information for KEYTRUDA® (pembrolizumab)
Immune-mediated pneumonitis, including fatal cases, occurred in patients
receiving KEYTRUDA. Pneumonitis occurred in 32 (2.0%) of 1567 patients
with melanoma, including Grade 1 (0.8%), 2 (0.8%), and 3 (0.4%)
pneumonitis. Pneumonitis occurred in 19 (3.5%) of 550 patients with
NSCLC, including Grade 2 (1.1%), 3 (1.3%), 4 (0.4%), or 5 (0.2%)
pneumonitis and 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 31 (2%) of 1567 patients with
melanoma, including Grade 2 (0.5%), 3 (1.1%), and 4 (0.1%) colitis.
Immune-mediated colitis occurred in 4 (0.7%) of 550 patients with NSCLC,
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.
Hepatitis occurred in 16 (1%) of 1567 patients with melanoma, including
Grade 2 (0.1%), 3 (0.7%), and 4 (0.1%) hepatitis. 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 13 (0.8%) of 1567 patients with melanoma,
including Grade 2 (0.3%), 3 (0.3%), and 4 (0.1%) hypophysitis.
Hypophysitis occurred in 1 (0.2%) of 550 patients with NSCLC, 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 for Grade 2; withhold or discontinue for
Grade 3 or 4 hypophysitis.
Hyperthyroidism occurred in 51 (3.3%) of 1567 patients with melanoma,
including Grade 2 (0.6%) and 3 (0.1%) hyperthyroidism. Hypothyroidism
occurred in 127 (8.1%) of 1567 patients with melanoma, including Grade 3
(0.1%) hypothyroidism. Hyperthyroidism occurred in 10 (1.8%) of 550
patients with NSCLC, including Grade 2 (0.7%) or 3 (0.3%)
hyperthyroidism. Hypothyroidism occurred in 38 (6.9%) of 550 patients
with NSCLC, 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
(pembrolizumab) 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.
Nephritis occurred in 7 (0.4%) of 1567 patients with melanoma including,
Grade 2 (0.2%), 3 (0.2%), and 4 (0.1%) nephritis. 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% (unless otherwise indicated) of 1567 patients
with melanoma: arthritis (1.6%), exfoliative dermatitis, bullous
pemphigoid, uveitis, myositis, Guillain-Barré syndrome, myasthenia
gravis, vasculitis, pancreatitis, hemolytic anemia, and partial seizures
arising in a patient with inflammatory foci in brain parenchyma. The
following clinically significant, immune-mediated adverse reactions
occurred in less than 1% of 550 patients with NSCLC: 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
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.
In Trial 6, KEYTRUDA was discontinued due to adverse reactions in 9% of
555 patients with advanced melanoma; adverse reactions leading to
discontinuation in more than one patient were colitis (1.4%), autoimmune
hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and
cardiac failure (0.4%). Adverse reactions leading to interruption of
KEYTRUDA occurred in 21% of patients; the most common (≥1%) was diarrhea
(2.5%). The most common adverse reactions with KEYTRUDA vs ipilimumab
were fatigue (28% vs 28%), diarrhea (26% with KEYTRUDA), rash (24% vs
23%), and nausea (21% with KEYTRUDA). Corresponding incidence rates are
listed for ipilimumab only for those adverse reactions that occurred at
the same or lower rate than with KEYTRUDA.
In Trial 2, KEYTRUDA was discontinued due to adverse reactions in 12% of
357 patients with advanced melanoma; the most common (≥1%) were general
physical health deterioration (1%), asthenia (1%), dyspnea (1%),
pneumonitis (1%), and generalized edema (1%). Adverse reactions leading
to interruption of KEYTRUDA occurred in 14% of patients; the most common
(≥1%) were dyspnea (1%), diarrhea (1%), and maculo-papular rash (1%).
The most common adverse reactions with KEYTRUDA vs chemotherapy were
fatigue (43% with KEYTRUDA), pruritus (28% vs 8%), rash (24% vs 8%),
constipation (22% vs 20%), nausea (22% with KEYTRUDA), diarrhea (20% vs
20%), and decreased appetite (20% with KEYTRUDA). Corresponding
incidence rates are listed for chemotherapy only for those adverse
reactions that occurred at the same or lower rate than with KEYTRUDA.
KEYTRUDA was discontinued due to adverse reactions in 14% of 550
patients with NSCLC. Serious adverse reactions occurred in 38% of
patients. The most frequent serious adverse reactions reported 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%).
No formal pharmacokinetic drug interaction studies have been conducted
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
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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.
Pamela Eisele, 267-305-3558
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