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Merck Announces Completion of Patient Enrollment in Phase III TRA-2°P-TIMI 50 Trial of SCH 530348, a Novel, Oral Antiplatelet PAR-1 Inhibitor

More than 26,000 Patients Enrolled in Global Trial Evaluating Investigational Antiplatelet Agent in the Long-Term Prevention of Cardiovascular Events

Whitehouse Station, NJ, Nov. 13, 2009- Merck announced today the completion of patient enrollment in the TRA 2°P-TIMI 50 clinical trial, a Phase III, randomized, double-blind, placebo-controlled, multinational study of SCH 530348, the company’s investigational antiplatelet protease activated receptor-1 (PAR-1) inhibitor. The study, conducted by the Thrombolysis in Myocardial Infarction (TIMI) Study Group, reached its target of more than 26,000 patients.

“TIMI 50 is the largest and most rapidly enrolling trial in our 25-year history,” commented Eugene Braunwald, M.D., Chairman of the TIMI Study Group. “We are very pleased with this achievement and look forward to completing this important clinical outcome trial,” he added.

The trial will assess the ability of SCH 530348, a thrombin receptor antagonist, or PAR-1 inhibitor, to prevent major cardiovascular events when added to current antiplatelet regimens (aspirin or aspirin + ADP inhibitor) in patients who have previously experienced a heart attack or stroke or who have peripheral arterial disease.

SCH 530348 is also being studied in the treatment of patients with acute coronary syndrome (ACS) in the ongoing Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRA-CER) trial, led by Duke Clinical Research Institute.

“The completion of enrollment in one of our two pivotal clinical outcome trials for this investigational medicine is a significant milestone achievement in the development of SCH 530348,” said Luciano Rossetti, M.D., senior vice president and head, Global Scientific Strategy, Merck Research Laboratories. ”Heart disease remains the leading cause of death worldwide, and we believe that this novel agent has the potential to address a significant unmet medical need,” he added.

Approximately 7.2 million people worldwide die each year from coronary heart disease, the most common cause of death in Europe and the United States. In spite of advances in antiplatelet and other preventive treatments, there remains a residual risk for further cardiovascular events in patients with established vascular disease.

About SCH 530348
The investigational antiplatelet SCH 530348 is being developed by Merck for the prevention and treatment of atherothrombotic events in patients with acute coronary syndrome and in those with prior myocardial infarction or stroke, as well as in patients with existing peripheral arterial disease.

SCH 530348 binds selectively to the thrombin receptor on platelets (PAR-1), and is therefore a member of a potentially new class of drugs called PAR-1 inhibitors. Importantly, Merck’s SCH 530348 is being investigated to determine whether it has the potential to provide clinical benefit through inhibition of this thrombin-mediated platelet activation without the liability of significantly increased major bleeding (when added to aspirin or aspirin plus an ADP inhibitor), a tendency associated with drugs that block thromboxane or ADP pathways. Specifically, this compound is being investigated as an oral antiplatelet agent for patients with established vascular disease, to evaluate whether it can provide incremental benefit when given with current standard antiplatelet (including aspirin and clopidogrel) and other antithrombotic therapies, without causing a significant increase in major bleeding.

The 1,030-patient TRA-PCI Phase II trial was published in the March 14, 2009 issue of The Lancet.

The U.S. Food and Drug Administration (FDA) has granted Fast Track designation to the compound. Fast Track designation allows FDA to expedite review of drugs and biologics for serious or life-threatening conditions which demonstrate the potential to address unmet medical needs.

About the Phase III Trials
SCH 530348 is currently being evaluated in two large-scale multinational, randomized, double-blind, placebo-controlled Phase III clinical trials.

The Phase III Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2°P-TIMI 50) trial, which has now completed full enrollment, is a randomized, double-blind, placebo-controlled study in patients with prior MI or stroke, as well as patients with existing peripheral arterial disease. Patients have been randomized to either placebo plus standard medical care (including aspirin and clopidogrel) or to SCH 530348 once daily plus standard medical care. This Phase III trial uses the 2.5 mg maintenance dose. The primary endpoint of the trial is the composite of cardiovascular death, MI, urgent coronary revascularization or stroke. The key secondary endpoint is the composite of cardiovascular death, MI or stroke. Patients will be followed for a minimum of one year. This Phase III trial is being conducted by the Thrombolysis in Myocardial Infarction (TIMI) Study Group. David Morrow, M.D. is the principal investigator.

The Phase III Thrombin Receptor Antagonist Clinical Event Reduction in acute coronary syndrome (TRA-CER) trial is a multinational, randomized, double-blind, placebo-controlled study in patients with non-ST-segment elevation acute coronary syndrome. Patients are being randomized to either placebo plus standard medical care (including aspirin or clopidogrel) or to SCH 530348 plus standard medical care. The Phase III TRA-CER trial uses the oral 40 mg loading dose and the 2.5 mg maintenance dose. The primary endpoint of the Phase III TRA-CER trial is the composite of cardiovascular death, MI, rehospitalization for ACS, urgent coronary revascularization or stroke. The key secondary endpoint is the composite of cardiovascular death, MI or stroke. Patients will be followed for a minimum of one year. This Phase III trial is being conducted by the Duke Clinical Research Institute, Durham, NC. .

About Merck
Today's Merck is working to help the world be well. Through our medicines, vaccines, biologic therapies, and consumer and animal 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 programs that donate and deliver our products to the people who need them. Merck. Be Well. For more information, visit www.merck.com.

Forward-Looking Statement
This communication includes “forward-looking statements” within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. Such statements may include, but are not limited to, statements about the benefits of the merger between Merck and Schering-Plough, including future financial and operating results, the combined company’s plans, objectives, expectations and intentions and other statements that are not historical facts. Such statements are based upon the current beliefs and expectations of Merck’s and Schering-Plough’s management and are subject to significant risks and uncertainties. Actual results may differ from those set forth in the forward-looking statements.

The following factors, among others, could cause actual results to differ from those set forth in the forward-looking statements: the possibility that the expected synergies from the merger of Merck and Schering-Plough will not be realized, or will not be realized within the expected time period, due to, among other things, the impact of pharmaceutical industry regulation and pending legislation that could affect the pharmaceutical industry; the risk that the businesses will not be integrated successfully; disruption from the merger making it more difficult to maintain business and operational relationships; Merck’s ability to accurately predict future market conditions; dependence on the effectiveness of Merck’s patents and other protections for innovative products; the risk of new and changing regulation and health policies in the U.S. and internationally and the exposure to 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 2008 Annual Report on Form 10-K, Schering-Plough’s Quarterly Report on Form 10-Q for the quarterly period ended September 30, 2009, the proxy statement filed by Merck on June 25, 2009 and each company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).

 

 

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