Investigational data from IMPROVE-IT to be
announced in Featured Clinical Research Session II
Merck (NYSE:MRK), known as MSD outside the United States and
Canada, announced today that new data from two trials of the
company’s cardiovascular medicines will be presented at the 2015
American College of Cardiology Annual Scientific Sessions (ACC.15),
March 14-16 in San Diego. In all, eleven data presentations from
company-sponsored studies will be presented at ACC.15, including
new data from the investigational IMPROVE-IT (IMProved Reduction of
Outcomes: VYTORIN Efficacy International Trial) study of VYTORIN
(ezetimibe/simvastatin) and exploratory sub-analyses of the TRA 2°P
TIMI 50 (Thrombin Receptor Antagonist in Secondary Prevention of
Atherothrombotic Ischemic Events) trial of ZONTIVITY
(vorapaxar).
“The American College of Cardiology’s 64th Annual
Scientific Sessions provide an opportunity for Merck to share new
data from two of the largest cardiovascular outcomes trials of
recent years,” said Dr. Daniel Bloomfield, vice president,
Cardiovascular Diseases, Merck Research Laboratories. “We are
pleased to share new data from these important studies with the
scientific community.”
The primary results from the IMPROVE-IT trial of VYTORIN, which
combines simvastatin with the non-statin ZETIA® (ezetimibe), were
presented in November 2014. VYTORIN and ZETIA are indicated for use
along with a healthy diet to reduce elevated LDL cholesterol in
patients with hyperlipidemia. The current U.S. Prescribing
Information for VYTORIN and ZETIA states that the effect of
ezetimibe on cardiovascular morbidity and mortality, alone or
incremental to statin therapy, has not been determined.
The TRA 2°P TIMI 50 study of ZONTIVITY (vorapaxar) supported the
May 2014 approval of that medicine for the reduction of thrombotic
cardiovascular events in patients with a history of myocardial
infarction (MI) or in patients with peripheral arterial disease
(PAD). In TRA 2°P TIMI 50, ZONTIVITY was shown to reduce the rate
of a combined endpoint of cardiovascular death, MI, stroke and
urgent coronary revascularization. The U.S. Prescribing Information
for ZONTIVITY includes a boxed warning regarding bleeding risk,
which states that ZONTIVITY is not for use in patients with a
history of stroke, transient ischemic attack (TIA) or intracranial
hemorrhage (ICH), or active pathological bleeding. Antiplatelet
agents, including ZONTIVITY, increase the risk of bleeding,
including ICH and fatal bleeding.
The following data will be presented at ACC.15:
IMPROVE-IT Data in Featured Clinical Research Session
II
- (Abstract #414-03) Reduction in
Total (First and Recurrent) Cardiovascular Events with
Ezetimibe/Simvastatin compared with Simvastatin Alone post-Acute
Coronary Syndromes in the IMPROVE-IT Trial. S. Murphy
- Monday, March 16 12:30 PM-12:45 PM PT.
Location: Room 6E.
TRA 2°P TIMI 50 Trial
- (Abstract #1131M-11) Vorapaxar and
Acute Limb Ischemia: Insights from the Thrombin Receptor Antagonist
in Secondary Prevention of Atherothrombotic Ischemic Events-TIMI 50
Trial. A. Gutierrez
- Saturday, March 14; 11:00 AM-11:10 AM
PT. Location: Vascular Medicine Moderated Poster Theater, Poster
Hall B1.
- (Abstract #905-04) The role of
Vorapaxar in Patients with Coronary Artery Bypass Grafting:
Findings from the TRA 2P-TIMI 50 Trial. E. Kosova
- Sunday, March 15; 10:57 AM-11:08 AM PT.
Location: Room 7B.
- (Abstract #1131M-05) Vorapaxar and
Peripheral Revascularization: Insights from the TRA2P-TIMI 50
Trial. I. Gilchrist
- Saturday, March 14; 10:15 AM-10:25 AM
PT. Location: Vascular Medicine Moderated Poster Theater, Poster
Hall B1.
- (Abstract #1131M-03) Statin
Intensity and Outcome in Patients with Peripheral Artery Disease:
Insights from the TRA2P-TIMI 50 Trial. I. Gilchrist
- Saturday, March 14; 10:00 AM-10:10 AM
PT. Location: Vascular Medicine Moderated Poster Theater, Poster
Hall B1.
Additional Merck-sponsored Data
- (Abstract #1125M-09) Baseline LDL-C
and Clinical Outcomes with Addition of Ezetimibe to Statin in
18,144 Patients Post ACS. R. Giugliano
- Saturday, March 14; 10:45 AM-10:55 AM
PT. Location: Acute Coronary Syndromes Moderated Poster Theater,
Poster Hall B1.
- (Abstract #1125M-07) Risk
Stratification for Cardiovascular Events in the IMPROVE-IT
Trial. E. Bohula
- Saturday, March 14; 10:30 AM-10:40 AM
PT. Location: Acute Coronary Syndromes Moderated Poster Theater,
Poster Hall B1.
- (Abstract #1133M-05) Cholesterol in
Remnant-Lipoproteins as Measured by Different Methods. P.
Toth
- Saturday, March 14; 10:15 AM-10:25 AM
PT. Location: Stable Ischemic Heart Disease Moderated Poster
Theater, Poster Hall B1.
- (Abstract #1194-364) Ezetimibe Does
Not Increase Fasting Glucose Levels More than Statins Alone in
Non-Diabetic, Hypercholesterolemic Patients. P. Toth
- Sunday, March 15; 9:45 AM-10:30 AM PT.
Location: Poster Hall B1.
- (Abstract #1211-119) Low
LDL-Cholesterol Target Achievement in Statin-Treated Patients in
Clinical Practice in China and Europe: Results of the Dyslipidemia
International Study (DYSIS) A. Gitt
- Sunday, March 15; 3:45 PM-4:30 PM PT.
Location: Poster Hall B1.
- (Abstract # 1261-347) Effect
of Beta-Blockade on Cardiovascular Event Rates in Patients with
Asymptomatic Aortic Stenosis C. Bang
- Monday, March 16; 9:45 AM-10:30 AM PT.
Location: Poster Hall B1.
About VYTORIN® (ezetimibe/simvastatin)
VYTORIN contains ezetimibe and simvastatin. VYTORIN is indicated
as adjunctive therapy to diet for the reduction of elevated total
cholesterol, LDL cholesterol, apolipoprotein B, triglycerides, and
non–HDL cholesterol, and to increase HDL cholesterol in patients
with primary (heterozygous familial and nonfamilial) hyperlipidemia
or mixed hyperlipidemia when diet alone is not enough.
The Prescribing Information for VYTORIN states that no
incremental benefit of VYTORIN on cardiovascular morbidity and
mortality over and above that demonstrated for simvastatin has been
established. VYTORIN is not indicated to reduce cardiovascular
events in patients who have presented with acute coronary
syndromes.
VYTORIN (ezetimibe/simvastatin) should not be taken with strong
CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, posaconazole,
voriconazole, HIV protease inhibitors, boceprevir, telaprevir,
erythromycin, clarithromycin, telithromycin, nefazodone, and
cobicistat-containing products); or with gemfibrozil, cyclosporine,
or danazol. VYTORIN also should not be taken by anyone with active
liver disease, unexplained persistent elevations of hepatic
transaminase levels, or hypersensitivity to the product; or by
women who are pregnant, nursing or may become pregnant.
Selected cautionary information about VYTORIN
All patients starting therapy with VYTORIN, or whose dose of
VYTORIN is being increased, should be advised of the risk of
myopathy, including rhabdomyolysis, and told to promptly report any
unexplained muscle pain, tenderness, or weakness particularly if
accompanied by malaise or fever or if muscle signs and symptoms
persist after discontinuing VYTORIN. VYTORIN should be discontinued
immediately if markedly elevated creatine kinase (CK) levels occur
or myopathy is diagnosed or suspected. VYTORIN contains
simvastatin, which occasionally causes myopathy manifested as
muscle pain, tenderness, or weakness with CK levels above 10 times
ULN. Myopathy sometimes takes the form of rhabdomyolysis with or
without acute renal failure secondary to myoglobinuria, and rare
fatalities have occurred. Predisposing factors for myopathy include
advanced age (≥65 years), female gender, uncontrolled
hypothyroidism, and renal impairment. The risk of myopathy,
including rhabdomyolysis, is dose related.
The 10/80 mg dose of VYTORIN should not be started in new
patients. The risk of myopathy, including rhabdomyolysis, is
greater in patients taking simvastatin 80 mg compared with other
statin therapies with similar or greater LDL cholesterol lowering
efficacy, and with lower doses of simvastatin. The 10/80 mg dose of
VYTORIN should be used only in patients who have been taking that
dose chronically (e.g., for 12 months or more) without evidence of
muscle toxicity. If a patient who is currently tolerating the 10/80
mg dose needs to be initiated on an interacting drug that is
contraindicated or is associated with a dose cap for simvastatin,
that patient should be switched to an alternative statin or
statin-based regimen with less potential for the drug-drug
interaction. Please read Warnings and Precautions in the
Prescribing Information for additional information.
In addition to drugs that are contraindicated because of an
increased risk of myopathy/rhabdomyolysis, grapefruit juice should
be avoided. Use caution when prescribing VYTORIN with a
fenofibrate, and immediately discontinue both drugs if myopathy is
diagnosed or suspected. Cases of myopathy, including
rhabdomyolysis, have been reported with simvastatin coadministered
with colchicine, and caution should be used when prescribing
VYTORIN (ezetimibe/simvastatin) with colchicine.
The dose of VYTORIN should not exceed 10/10 mg daily in patients
receiving verapamil, diltiazem or dronedarone, and 10/20 mg daily
in patients receiving amiodarone, amlodipine or ranolazine. For
patients with homozygous familial hypercholesterolemia (HoFH)
taking lomitapide, the dose should not exceed 10/20 mg/day (or
10/40 mg/day for patients who have previously taken simvastatin 80
mg/day chronically, e.g., for 12 months or more, without evidence
of muscle toxicity); patients initiating lomitapide should have
their dose of VYTORIN reduced by 50%. The benefits of combined use
of VYTORIN with these drugs, other fenofibrates, or niacin (≥1
g/day) should be carefully weighed against the potential risk of
myopathy/rhabdomyolysis. Caution should be used when Chinese
patients taking niacin (≥1 g/day) are coadministered doses of
VYTORIN exceeding 10/20 mg/day; Chinese patients should not receive
VYTORIN 10/80 mg with niacin.
Persistent elevations in hepatic transaminase can occur. Liver
function tests should be performed at treatment initiation and
thereafter when clinically indicated. If serious liver injury with
clinical symptoms and/or hyperbilirubinemia or jaundice occurs
during treatment, therapy should be interrupted promptly and not
restarted unless an alternate etiology is found.
Increases in HbA1c and fasting serum glucose levels have been
reported with statins, including simvastatin.
In clinical trials, the most commonly reported side effects,
regardless of cause, included headache (5.8 percent), increased ALT
(3.7 percent), myalgia (3.6 percent), upper respiratory tract
infection (3.6 percent), and diarrhea (2.8 percent).
VYTORIN tablets contain ezetimibe and simvastatin: 10 mg of
ezetimibe and 10, 20, 40, or 80 mg of simvastatin (VYTORIN 10/10,
10/20, 10/40, or 10/80 mg, respectively). The usual dosage range is
10/10 mg/day to 10/40 mg/day; patients should not be titrated to
the restricted 10/80-mg dose.
About ZETIA (ezetimibe)
ZETIA, administered alone or in combination with a statin, is
indicated as adjunctive therapy to diet for the reduction of
elevated total cholesterol, LDL cholesterol, apolipoprotein B, and
non-HDL cholesterol in patients with primary (heterozygous familial
and non-familial) hyperlipidemia when diet alone is not enough.
The Prescribing Information for ZETIA states that the effect of
ZETIA on cardiovascular morbidity and mortality has not been
determined. ZETIA is not indicated for use with a statin to further
reduce cardiovascular events in patients who have presented with
acute coronary syndromes.
ZETIA (ezetimibe) should not be taken by people with
hypersensitivity to any component of the medication. Statin
contraindications also apply when ZETIA is used with these drugs:
statins are contraindicated in patients with active liver disease,
unexplained persistent elevations in hepatic transaminase levels
and in pregnant and nursing women. Refer to individual statin
labels for details about who should not take that statin.
Selected cautionary information about ZETIA
When using ZETIA with a statin, also follow the label
recommendations for that specific statin.
When ZETIA was coadministered with a statin, consecutive
elevations in hepatic transaminase levels (greater than or equal to
3 times ULN) were slightly higher (1.3 percent) than those of
statins alone (0.4 percent). Liver function tests should be
performed when ZETIA is added to statin therapy and according to
statin recommendations. Should an increase in ALT or AST greater
than or equal to 3 times ULN persist, consider withdrawal of ZETIA
and/or the statin.
Patients should be advised to promptly report muscle pain,
tenderness, or weakness. Risk for skeletal muscle toxicity
increases with higher statin doses, advanced age (>65),
hypothyroidism, renal impairment, and depending on the statin used,
concomitant use of other drugs. Discontinue drug if myopathy is
diagnosed or suspected.
ZETIA is not recommended in patients with moderate to severe
hepatic impairment.
The coadministration of ZETIA with fibrates other than
fenofibrate is not recommended until use in patients is adequately
studied. Exercise caution when using ZETIA and cyclosporine
concomitantly because exposure to both drugs is increased.
Cyclosporine concentrations should be monitored in these
patients.
ZETIA should be used in pregnant or nursing women only if the
benefit outweighs the risk.
In clinical trials, regardless of causality assessment, the most
frequent side effects for ZETIA coadministered with a statin versus
a statin alone included nasopharyngitis (3.7 percent vs 3.3
percent), myalgia (3.2 percent vs 2.7 percent), upper respiratory
tract infection (2.9 percent vs 2.8 percent), arthralgia (2.6
percent vs 2.4 percent), and diarrhea (2.5 percent vs 2.2 percent);
for ZETIA administered alone vs placebo: upper respiratory tract
infection (4.3 percent vs 2.5 percent), diarrhea (4.1 percent vs
3.7 percent), arthralgia (3.0 percent vs 2.2 percent), sinusitis
(2.8 percent vs 2.2 percent), pain in extremity (2.7 percent vs 2.5
percent), and fatigue (2.4 percent vs 1.5 percent).
About ZONTIVITY (vorapaxar)
ZONTIVITY is indicated for the reduction of thrombotic
cardiovascular events in patients with a history of MI or with PAD.
ZONTIVITY has been shown to reduce the rate of a combined endpoint
of cardiovascular death, MI, stroke, and urgent coronary
revascularization. ZONTIVITY inhibits the protease-activated
receptor-1 (PAR-1), the primary receptor for thrombin, which is
considered to be the most potent activator of platelets. The PAR-1
pathway participates in the formation of blood clots through the
activation and aggregation of platelets.
ZONTIVITY is a once-daily tablet containing 2.08 mg vorapaxar,
equivalent to 2.5 mg vorapaxar sulfate. ZONTIVITY was studied only
as an addition to aspirin and/or clopidogrel and should be used
with aspirin and/or clopidogrel according to their indications or
standard of care. There is no experience with use of ZONTIVITY
alone as the only administered antiplatelet agent.
Additional selected safety information about
ZONTIVITY
ZONTIVITY is contraindicated in patients with a history of
stroke, TIA, or ICH and in patients with active pathological
bleeding such as ICH or peptic ulcer. Discontinue ZONTIVITY in
patients who experience a stroke, TIA, or ICH.
Antiplatelet agents, including ZONTIVITY, increase the risk of
bleeding, including ICH and fatal bleeding. ZONTIVITY increases the
risk of bleeding in proportion to the patient’s underlying bleeding
risk. Physicians should consider the underlying risk of bleeding
before initiating ZONTIVITY.
General risk factors for bleeding include older age, low body
weight, reduced renal or hepatic function, and history of bleeding
disorders. Use of certain concomitant medications (e.g.,
anticoagulants, fibrinolytic therapy, chronic nonsteroidal
anti-inflammatory drugs, selective serotonin reuptake inhibitors,
serotonin norepinephrine reuptake inhibitors) also increases the
risk of bleeding. Avoid concomitant use of warfarin or other
anticoagulants.
Withholding ZONTIVITY for a brief period will not be useful in
managing an acute bleeding event because, due to its long
half-life, significant inhibition of platelet aggregation remains
four weeks after discontinuation. There is no known treatment to
reverse the antiplatelet effect of ZONTIVITY.
Strong CYP3A inhibitors increase and inducers decrease ZONTIVITY
exposure. Avoid concomitant use of ZONTIVITY with strong CYP3A4
inhibitors or inducers.
Based on the increased inherent risk of bleeding in patients
with severe hepatic impairment, ZONTIVITY is not recommended in
these patients.
Bleeding, including life-threatening and fatal bleeding, is the
most commonly reported adverse reaction with ZONTIVITY (vorapaxar).
Among post-MI or PAD patients with no history of stroke or TIA,
three-year bleeding rates (shown with hazard ratios and 95%
confidence intervals) in patients who added ZONTIVITY (vorapaxar)
or placebo, respectively, to aspirin and/or clopidogrel were:
—GUSTO moderate or severe bleeding,a 3.7% vs 2.4%, HR 1.55
(1.30-1.86)
—GUSTO severe bleeding,a 1.3% vs 1.0%, HR 1.24 (0.92-1.66)
—Any GUSTO bleeding (severe/moderate/mild),a 27.7% vs 19.8%, HR
1.52 (1.43-1.61)
—ICH, 0.6% vs 0.4%, HR 1.46 (0.92-2.31)
—Fatal bleeding, 0.2% vs 0.2%, HR 1.15 (0.56-2.36)
—Clinically significant bleeding,b 15.5% vs 10.9%, HR 1.47
(1.35-1.60)
Additional Information about the IMPROVE-IT Trial
IMPROVE-IT was a multi-center, randomized, double-blind active
comparator trial of 18,144 high-risk patients presenting with acute
coronary syndromes (ACS), including unstable angina (UA),
non-ST-segment elevation acute myocardial infarction (NSTEMI), and
ST-segment elevation acute myocardial infarction (STEMI). Patients
were randomized to receive ezetimibe/simvastatin (VYTORIN) or
simvastatin alone, and were followed for up to nine years, with a
median clinical follow-up of approximately six years. The primary
efficacy endpoint was the composite of cardiovascular death,
non-fatal MI, non-fatal stroke, re-hospitalization for ACS, or
coronary revascularization (occurring 30 days or more after the
initial event).
Additional Information about the TRA 2°P TIMI 50
Trial
TRA 2°P TIMI 50 was a multi-center, randomized, double-blind,
placebo-controlled trial of 26,449 patients with a history of
spontaneous MI within the prior two weeks to twelve months,
ischemic stroke, or documented (symptomatic) PAD. Among all
randomized patients, 20,170 had a history of MI or PAD and had no
history of stroke or TIA (contraindications for ZONTIVITY include a
history of stroke or TIA). Patients were randomized to receive
daily treatment with ZONTIVITY or placebo in addition to standard
of care that included aspirin and/or a thienopyridine (principally
clopidogrel), and were followed for up to four years, with a median
follow-up of 2.5 years. The primary efficacy endpoint was the
composite of CV death, MI, stroke, and UCR, and the key secondary
efficacy endpoint was the composite of CV death, MI, and
stroke.
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 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.
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; 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 VYTORIN
(ezetimibe/simvastatin) at
http://www.merck.com/product/usa/pi_circulars/v/vytorin/vytorin_pi.pdf
and the Patient Information for VYTORIN at
http://www.merck.com/product/usa/pi_circulars/v/vytorin/vytorin_ppi.pdf
Please see Prescribing Information for ZETIA (ezetimibe)
at
http://www.merck.com/product/usa/pi_circulars/z/zetia/zetia_pi.pdf
and the Patient Information for ZETIA at
http://www.merck.com/product/usa/pi_circulars/z/zetia/zetia_ppi.pdf
Please see Prescribing Information, including Boxed Warning,
for ZONTIVITY (vorapaxar) at
http://www.merck.com/product/usa/pi_circulars/z/zontivity/zontivity_pi.pdf
and Medication Guide for ZONTIVITY at
http://www.merck.com/product/usa/pi_circulars/z/zontivity/zontivity_mg.pdf
a GUSTO severe bleeding: fatal, intracranial, or bleeding with
hemodynamic compromise requiring intervention; GUSTO moderate
bleeding: bleeding requiring transfusion of whole blood or packed
red blood cells without hemodynamic compromise.
b Clinically significant bleeding: bleeding requiring medical
attention including ICH, or clinically significant overt signs of
hemorrhage with a drop in Hgb ≥3 g/dL (or, when Hgb is not
available, an absolute drop in Hct ≥9%).
MerckMedia:Pamela Eisele, 267-305-3558orMichael Close,
267-305-1211orInvestor:Justin Holko, 908-423-5088
Merck (NYSE:MRK)
Historical Stock Chart
From Mar 2024 to Apr 2024
Merck (NYSE:MRK)
Historical Stock Chart
From Apr 2023 to Apr 2024