New Data Shows Anticlotting Medicine, AGGRASTAT(R), Lowers Incidence of Heart Attack,...

New Data Shows Anticlotting Medicine, AGGRASTAT(R), Lowers Incidence of Heart Attack, in Patients Who Respond Poorly to Aspirin or Clopidogrel, after Elective Coronary Angioplasty

PHILADELPHIA--(Business Wire)--
Antiplatelet medicine, AGGRASTAT(R) (tirofiban HCL), a
glycoprotein IIb/IIIa inhibitor, has been shown to significantly lower
the incidence of heart attack after elective coronary angioplasty, in
patients with coronary artery disease who have shown poor response to
standard oral antiplatelet agents such as aspirin and clopidogrel.(1)
These results were announced today at the Annual European Society of
Cardiology Congress in Munich, Germany.

"These findings are significant in that we demonstrate a proof of
concept for a new treatment strategy in a patient segment whose needs
have so far remained unaddressed - managing for the increased risk of
thrombotic events due to non-responsiveness of patients to standard
oral antiplatelets such as aspirin or clopidogrel," said Dr Marco
Valgimigli, Chair of Cardiology, University of Ferrara, Italy and
principal investigator of the 3T/2R Study (Tailoring Treatment with
Tirofiban in patients showing Resistance to aspirin and/or Resistance
to clopidogrel).

Inhibition of platelet aggregation following an intake of aspirin
or clopidogrel varies greatly among patients, and previous studies
have shown that poor response to oral antiplatelet agents increases
the risk of thrombotic events, especially after coronary
angioplasty.(1) It was previously unknown if this reflected suboptimal
platelet inhibition per se which might benefit from alternative or
more potent antiplatelet agents.

Enrolled in the study were 263 patients who were poor responders
to aspirin and/or clopidogrel, based upon a point-of-care assay, who
underwent elective coronary angioplasty at ten European sites for
stable or low-risk unstable coronary artery disease. Patients were
randomly assigned in a double blind manner to receive either
AGGRASTAT(R) or placebo on top of standard aspirin and clopidogrel
therapy.(1) The primary end point was the occurrence of periprocedural
myocardial infarction, as defined by an increase in Troponin I or T
within 48 hours, and was observed in 20.4 percent of patients treated
with AGGRASTAT(R), compared to 35.1 percent of patient treated with
placebo.(1) This resulted in a significant reduction of major adverse
cardiovascular events within 30 days in the AGGRASTAT(R) group
compared to the placebo group (21.2 percent versus 36.6 percent,
respectively; p=0.0065).(1) The incidence of bleeding was low and did
not differ between the two groups.(1)

"Current treatment strategies for patients with coronary artery
disease ignore the individual response to antiplatelet agents, and
likewise fail to identify therapeutic targets for platelet reactivity
necessary to intensify treatment," said Dr Paul Gurbel, Director of
Cardiovascular Research, Centre for Thrombosis Research, Sinai
Hospital, Baltimore, USA. "These findings illustrate the efficacy and
safety of AGGRASTAT(R) in treating poor responders to aspirin or
clopidogrel, as compared to standard care. This study shows that by
assessing response to standard antiplatelet agents by a point-of-care
assay, intensity of treatment can be modulated accordingly."

Dr Gurbel further commented, "These data are in accordance with
our earlier results from the CLEAR PLATELETS studies that have
demonstrated the strong association between high periprocedural
platelet reactivity and the risk of in-hospital myocardial infarction
in patients undergoing elective stenting. The use of glycoprotein
IIb/IIIa inhibitors, in patients identified as poor responders to oral
antiplatelet agents by objective measurements of platelet function,
makes perfect sense and deserves greater attention in future studies."

"These data findings are extremely encouraging for this patient
population and we believe it reinforces the potential benefits of
high-dose bolus AGGRASTAT(R)," said John Vavricka, President and Chief
Executive Officer of Iroko Pharmaceuticals. "Iroko is committed to
furthering clinical research in this area, and exploring
AGGRASTAT(R)'s potential for patients who do not respond to oral
anti-platelet therapy."

In January of 2008, Iroko Pharmaceuticals acquired all non-US
commercial rights to AGGRASTAT(R) from Merck & Co., Inc. The 3T/2R
study was initiated and conducted by the University of Ferrara, Italy
with an unrestricted grant from Merck & Co., Inc. and Iroko.

About AGGRASTAT(R)

AGGRASTAT(R), a glycoprotein IIb/IIIa inhibitor, is indicated for
the prevention of early myocardial infarction in patients presenting
with unstable angina or non-Q-wave myocardial infarction with the last
episode of chest pain occurring within 12 hours and with ECG changes
and/or elevated cardiac enzymes. Patients most likely to benefit from
AGGRASTAT(R) treatment are those at high risk of developing myocardial
infarction within the first 3-4 days after onset of acute angina
symptoms including for instance those that are likely to undergo an
early PTCA.

In most patients, AGGRASTAT(R) should be administered
intravenously, at an initial rate of 0.4 mcg/kg/min for 30 minutes and
then continued at 0.1 mcg/kg/min. For complete information, please
refer to the product's prescribing information. AGGRASTAT(R) is
intended for use with acetylsalicylic acid and unfractionated heparin.

AGGRASTAT(R) (tirofiban hydrochloride) is contraindicated in
patients with known hypersensitivity to any component of the product;
active internal bleeding or a history of bleeding diathesis within the
previous 30 days; or a history of intracranial hemorrhage,
intracranial neoplasm, arteriovenous malformation, or aneurysm. Other
contraindications to AGGRASTAT(R) include: a history of
thrombocytopenia following prior exposure to AGGRASTAT(R); history of
stroke within 30 days or any history of hemorrhagic stroke; major
surgical procedure or severe physical trauma within the previous
month; or history, symptoms, or findings suggestive of aortic
dissection. AGGRASTAT(R) is also contraindicated in patients with:
severe hypertension (systolic blood pressure greater than180 mmHg
and/or diastolic blood pressure greater than110 mmHg); concomitant use
of another parenteral GP IIb/IIIa inhibitor; or acute pericarditis.

Bleeding is the most common complication encountered during
therapy with AGGRASTAT(R). Administration of AGGRASTAT(R) is
associated with an increase in bleeding events classified as both
major and minor bleeding events, by criteria developed by the
Thrombolysis in Myocardial Infarction Study group (TIMI). Most major
bleeding associated with AGGRASTAT(R) occurs at the arterial access
site for cardiac catheterization. Fatal bleedings have been reported.
AGGRASTAT(R) should be used with caution in patients with platelet
count less than150,000/mm3, in patients with hemorrhagic retinopathy,
and in chronic hemodialysis patients. Because AGGRASTAT(R) inhibits
platelet aggregation; caution should be employed when it is used with
other drugs that affect hemostasis. The safety of AGGRASTAT(R) when
used in combination with thrombolytic agents has not been established.
During therapy with AGGRASTAT(R), patients should be monitored for
potential bleeding. When bleeding cannot be controlled with pressure,
infusion of AGGRASTAT(R) and heparin should be discontinued.

The following additional adverse reactions have been reported in
post- marketing experience: bleeding, intracranial bleeding,
retroperitoneal bleeding, hemopericardium, and pulmonary (alveolar)
hemorrhage. Fatal bleedings have been reported; body as a whole: acute
and/or severe decreases in platelet counts which may be associated
with chills, low grade fever, or bleeding complications;
hypersensitivity; rash and/or hives.

Please refer to the specific Prescribing Information for your
country for complete warnings and precautions.

About Iroko

Iroko is a pharmaceutical company focused on acquiring,
developing, and maximizing the potential of currently marketed
pharmaceutical products on a worldwide basis. Iroko applies
concentrated selling and marketing efforts and product life cycle
management strategies focused on developing new and relevant
formulations and indications that benefit patient health. For more
information, visit www.iroko.com.

About Merck

Merck & Co., Inc. is a global research-driven pharmaceutical
company dedicated to putting patients first. Established in 1891,
Merck currently discovers, develops, manufactures and markets vaccines
and medicines to address unmet medical needs. The company devotes
extensive efforts to increase access to medicines through far-reaching
programs that not only donate Merck medicines but help deliver them to
the people who need them. Merck also publishes unbiased health
information as a not-for-profit service.

-ENDS-

References

(1) Valgimigli M, Campo Gianluca, de Cesare N, Meliga E et al. A
double-blind randomised multicentre trial of tailored infusion of
tirofiban in poor aspirin and/or clopidogrel responders undergoing
elective percutaneous coronary intervention. Presented at ESC, 2
September 2008

Edelman
Katie Turner Samuels, +447790 552 210
Katie.Turner-Samuels@edelman.com

Copyright Business Wire 2008