New Analyses from the IMPROVE-IT Outcomes Study of VYTORIN® (ezetimibe and simvastatin) and the TECOS Cardiovascular Safety Trial of JANUVIA® (sitagliptin) Will Be Presented at the European Society of Cardiology Congress

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August 20, 2015 7:30 am ET

Additional Real-World Analyses from DYSIS and DYSIS II Assessing the Treatment of Dyslipidemia to be Presented

Merck (NYSE:MRK), known as MSD outside the United States and Canada,
announced today that new analyses from the investigational IMPROVE-IT
(IMProved Reduction of Outcomes: VYTORIN Efficacy International Trial)
study of VYTORIN® (ezetimibe and simvastatin), the TECOS
(Trial Evaluating Cardiovascular Outcomes with Sitagliptin)
cardiovascular safety trial of JANUVIA® (sitagliptin), and
real-world data from the Dyslipidemia International Study (DYSIS I and
DYSIS II) will be presented at the upcoming European Society of
Cardiology (ESC) Congress 2015, held Aug. 29 to Sept. 2, 2015.
IMPROVE-IT was designed to evaluate the cardiovascular benefit of the
combination of ezetimibe and simvastatin compared to simvastatin alone.
The TECOS cardiovascular safety trial was designed to assess the
cardiovascular safety of Merck’s DPP-4 inhibitor, JANUVIA. In all, Merck
has 13 data presentations at this year’s ESC.

“At this year’s European Society of Cardiology Congress, we are pleased
to share new data from two important studies – IMPROVE-IT and
the TECOS cardiovascular safety trial – which have already
added substantially to our knowledge of cardiovascular disease and the
cardiovascular safety profile of sitagliptin, respectively,” said Dr.
Roy Baynes, senior vice president, global clinical development, Merck
Research Laboratories.

The primary results from IMPROVE-IT, which enrolled 18,144 high-risk
patients presenting with acute coronary syndromes (ACS), were presented
in November 2014 at the American Heart Association Scientific Sessions
and published in The New England Journal of Medicine in June
2015. VYTORIN and ZETIA® (ezetimibe) 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. Merck has submitted the data from
IMPROVE-IT to regulatory authorities in the U.S. and European Union to
support a new indication for reduction of major cardiovascular events
for VYTORIN® and ZETIA®.

TECOS was an event-driven study of more than 14,000 patients that
evaluated the long-term cardiovascular safety of the addition of JANUVIA
to usual care, compared to usual care without JANUVIA, in patients with
type 2 diabetes and established cardiovascular disease. The primary
results of the TECOS cardiovascular safety trial were presented at the
75th Scientific Sessions of the American Diabetes Association and
published simultaneously in the New England Journal of Medicine
in June 2015.

Indications and Limitations of Use for JANUVIA®
(sitagliptin) 25 mg, 50 mg and 100 mg tablets

JANUVIA is indicated, as an adjunct to diet and exercise, to improve
glycemic control in adults with type 2 diabetes mellitus. JANUVIA should
not be used in patients with type 1 diabetes or for the treatment of
diabetic ketoacidosis. JANUVIA has not been studied in patients with a
history of pancreatitis. It is unknown whether patients with a history
of pancreatitis are at increased risk of developing pancreatitis while
taking JANUVIA.

Selected Important Risk Information about JANUVIA

JANUVIA is contraindicated in patients with a history of a serious
hypersensitivity reaction to sitagliptin, such as anaphylaxis or
angioedema.

There have been no clinical studies establishing conclusive evidence of
macrovascular risk reduction with JANUVIA or with any other antidiabetic
drug.

Analysis of DYSIS and DYSIS II

The cross-sectional, observational study DYSIS examined lipid goal
attainment among statin-treated patients including patients suffering
from coronary heart disease (CHD), diabetes, chronic kidney disease or
peripheral atherosclerotic disease. DYSIS enrolled approximately 60,000
patients from 30 countries from regular clinical practice such as
physicians’ offices and hospital outpatient wards between 2008 and 2012.
DYSIS II, a continuation of DYSIS study evaluating lipid goal
attainment, enrolled approximately 4,000 ACS patients and 7,000 CHD
patients globally between 2012 and 2014.

The following data will be presented at ESC Congress 2015:

TECOS Cardiovascular Safety Trial Data Analysis

  • (Oral Presentation) Trial Evaluating Cardiovascular Outcomes
    with Sitagliptin in Patients with Type 2 Diabetes: TECOS

    • Monday, Aug. 31: 11:00AM – 12:30PM GMT; Presentation 11:00AM –
      11:10AM GMT. Location: London – Main Auditorium, Hot Line III –
      Diabetes Mellitus/Pharmacology

IMPROVE-IT Data Analysis

  • (Oral Presentation) Safety and Efficacy of Long-term Very Low
    Achieved LDL-C in the IMPROVE-IT Trial

    • Saturday, Aug. 29: 11:00AM – 12:30PM GMT; Presentation 11:20AM
      – 11:37AM GMT. Location: San Marino – Village 2, Low-Density
      Lipoprotein Cholesterol: How Low and How to Lower?
  • (Moderated Poster) Prospective Evaluation of Cancer in 18,144
    Patients Randomized to Ezetimibe vs Placebo: a Prespecified Analysis
    from the IMPROVE-IT Trial

    • Sunday, Aug. 30: 10:00AM – 11:00AM GMT; Presentation 10:51AM –
      11:00AM GMT. Location: Poster Area, Managing Lipids – Statins and
      Beyond
  • (Poster Session) Muscle Related Complaints, Serious Adverse
    Events and Drug Discontinuations in 17,706 Subjects Randomized to
    Simvastatin or Ezetimibe/Simvastatin in the IMPROVE-IT Study

    • Tuesday, Sept. 1: 2:00PM – 4:00PM GMT. Location: Poster Area,
      Surveillance of Risk Factors and Interventions
  • (Best Posters) Achievement Of Dual LDL-C (<70 mg/dL) And hs-CRP
    (<2 mg/L) Goals More Frequent With Addition Of Ezetimibe and
    Associated With Better Outcomes In IMPROVE-IT

    • Tuesday, Sept. 1: 2:00PM – 4:00PM GMT. Location: Poster Area,
      Best Posters in Medical Therapy of Stable Coronary Artery Disease
  • (Oral Presentation) Incidence of New Onset Diabetes in the
    IMPROVE-IT Trial: Does Adding Ezetimibe to Simvastatin Increase Risk
    Compared to Simvastatin Alone?

    • Tuesday, Sept. 1: 2:00PM – 3:30PM GMT; Presentation
      2:30PM-2:45PM GMT. Location: Hyde Park – The Hub, Clinical Trial
      Update III – Pharmacology & Therapy.
  • (Oral Presentation) Benefit Of Adding Ezetimibe To Statin
    Therapy On Cardiovascular Outcomes And Safety In Patients With Vs.
    Without Diabetes: The IMPROVE-IT Trial

    • Sunday, Aug. 30: 2:00PM – 3:30PM GMT; Presentation 2:15PM –
      2:30PM GMT. Location: Hyde Park – The Hub, Clinical Trial Update I
      – Cardiovascular Diseases: Prevention, Outcomes, Quality.

DYSIS & DYSIS II Data Analysis

  • (Poster Session) High Prevalence of Persistent Lipid
    Abnormalities Among Coronary Patients: The Dyslipidemia International
    Study (DYSIS) II Global Results

    • Sunday, Aug. 30: 8:30AM – 12:30PM GMT. Location: Poster Area,
      Treatment Strategies and Adherence: Can We Decrease Risk?
  • (Poster Session) Are Coronary Patients on Lipid-lowering Therapy
    in Europe Achieving the Recommended LDL-C Target? Results from the
    Dyslipidemia International Study (DYSIS) II Europe

    • Sunday, Aug. 30: 8:30AM – 12:30PM GMT. Location: Poster Area,
      Strategies and Adherence: Can We Decrease Risk?
  • (Poster Session) Prevalence of Lipid Abnormalities Among
    Coronary Patients Remains High in the Middle East/Africa Region: The
    Dyslipidemia International Study (DYSIS) II MEA results

    • Sunday, Aug.30: 8:30AM – 12:30PM GMT. Location: Poster Area,
      Strategies and Adherence: Can We Decrease Risk?
  • (Poster Session) LDL-C Target Attainment Remains Low Among
    Treated Coronary Patients in Asia-Pacific: The Dyslipidemia
    International Study (DYSIS) II AP Results

    • Sunday, Aug. 30: 8:30AM – 12:30PM GMT. Location: Poster Area,
      Strategies and Adherence: Can We Decrease Risk?
  • (Poster Session) Unexpected High Prevalence of Possible and
    Probable FH in Clinical Practice – Results of DYSIS I

    • Sunday, Aug. 30: 8:30AM – 12:30PM GMT. Location: Poster
      Area, Classical and New Risk Factors for Cardiovascular Disease
  • (Oral Presentation) Low LDL-cholesterol Target Achievement in
    Statin-treated Patients in Clinical Practice in China and Europe:
    Results of the Dyslipidemia International Study (DYSIS)

    • Saturday, Aug. 29: 11:00AM – 12:30PM GMT; Presentation 11:37AM
      – 11:54 AM GMT. Location: San Marino – Village 2 – Low-Density
      Lipoprotein Cholesterol: How Low and How to Lower?

About VYTORIN® (ezetimibe and 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 and 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 and 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).

Selected Important Risk Information about JANUVIA® (continued)

There have been postmarketing reports of acute pancreatitis, including
fatal and nonfatal hemorrhagic or necrotizing pancreatitis, in patients
taking JANUVIA. After initiating JANUVIA, observe patients carefully for
signs and symptoms of pancreatitis. If pancreatitis is suspected,
promptly discontinue JANUVIA and initiate appropriate management.

Assessment of renal function is recommended prior to initiating JANUVIA
and periodically thereafter. A dosage adjustment is recommended in
patients with moderate or severe renal insufficiency and in patients
with end-stage renal disease requiring hemodialysis or peritoneal
dialysis. Caution should be used to ensure that the correct dose of
JANUVIA is prescribed.

There have been postmarketing reports of worsening renal function,
including acute renal failure, sometimes requiring dialysis. A subset of
these reports involved patients with renal insufficiency, some of whom
were prescribed inappropriate doses of sitagliptin.

When JANUVIA was used in combination with a
sulfonylurea or insulin, medications known to cause hypoglycemia, the
incidence of hypoglycemia was increased over that of placebo. Therefore,
a lower dose of sulfonylurea or insulin may be required to reduce the
risk of hypoglycemia.

The incidence (and rate) of hypoglycemia based on all reports of
symptomatic hypoglycemia were: 12.2 percent (0.59 episodes per
patient-year) for JANUVIA 100 mg in combination with glimepiride (with
or without metformin), 1.8 percent (0.24 episodes per patient-year) for
placebo in combination with glimepiride (with or without metformin),
15.5 percent (1.06 episodes per patient-year) for JANUVIA (sitagliptin)
100 mg in combination with insulin (with or without metformin), and 7.8
percent (0.51 episodes per patient-year) for placebo in combination with
insulin (with or without metformin).

There have been postmarketing reports of serious hypersensitivity
reactions in patients treated with JANUVIA (sitagliptin),
such as anaphylaxis, angioedema and exfoliative skin conditions
including Stevens-Johnson syndrome. Onset of these reactions occurred
within the first 3 months after initiation of treatment with JANUVIA®,
with some reports occurring after the first dose. If a hypersensitivity
reaction is suspected, discontinue JANUVIA, assess for other potential
causes for the event, and institute alternative treatment for diabetes.

Angioedema has also been reported with other dipeptidyl peptidase-4
(DPP-4) inhibitors. Use caution in a patient with a history of
angioedema with another DPP-4 inhibitor because it is unknown whether
such patients will be predisposed to angioedema with JANUVIA.

There have been no clinical studies establishing conclusive evidence of
macrovascular risk reduction with JANUVIA or with any other antidiabetic
drug. In clinical studies, the adverse reactions reported, regardless of
investigator assessment of causality, in greater than or equal to 5
percent of patients treated with JANUVIA as monotherapy and in
combination therapy, and more commonly than in patients treated with
placebo, were upper respiratory tract infection, nasopharyngitis and
headache.

About Merck

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be well. Merck is known as MSD outside the United States and Canada.
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demonstrate our commitment to increasing access to health care through
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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. 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
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by competitors; challenges inherent in new product development,
including obtaining regulatory approval; the company’s ability to
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The company undertakes no obligation to publicly update any
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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 VYTORIN®
(ezetimibe and 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 for JANUVIA®
(sitagliptin) at
http://www.merck.com/product/usa/pi_circulars/j/januvia/januvia_pi.pdf
and Medication Guide for JANUVIA at
http://www.merck.com/product/usa/pi_circulars/j/januvia/januvia_mg.pdf.

Merck
Media:
Pamela Eisele, 267-305-3558
or
Kim Hamilton, 908-391-0131
or
Investor:
Justin Holko, 908-740-1879

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