Merck Stands Behind Original APPROVe Study Results; Increased Relative Risk Observed Beginning After 18 Months.

WHITEHOUSE STATION, N.J. -- Merck & Co., Inc. reaffirmed in an open letter today to the scientific community that it stands behind the original results of the APPROVe study published in the New England Journal of Medicine (NEJM) in 2005, in which there was an increased relative risk for confirmed thrombotic cardiovascular events for VIOXX compared to placebo beginning after 18 months of continuous daily treatment. The Company's letter follows a correction notice published by the NEJM editors.

Earlier this year, on May 30, Merck notified the NEJM, the APPROVe study authors, regulatory authorities and the public that it had discovered the need for a correction in the description of a statistical method used to analyze certain data in the study.

"As we have said previously and reaffirm today, this correction did not change the data in the APPROVe study or its results," said Peter S. Kim, president of Merck Research Laboratories. "It is important to understand that the correction centered on the description of a single statistical method. Merck used a number of analytical and graphical methods to evaluate whether the relative risk changed over time. Taken together and consistent with good statistical practice, these methods confirm that the relative risk changes over time. In the APPROVe base study, the increased relative risk was observed beginning after 18 months."

The error was in the description of the test of proportional hazards reported in the study published by the NEJM. This type of test is designed to evaluate whether the relative risk is the same over time or changes over time.

"The scientific debate surrounding the APPROVe study in no way changes our commitment to defending the VIOXX litigation on a case-by-case basis," said Kenneth C. Frazier, senior vice president and general counsel of Merck. "The individual facts of each VIOXX case are very important. Unfortunately, thrombotic cardiovascular events are a major health problem and stem from many risk factors unrelated to VIOXX."

The VIOXX cardiovascular data analysis plan called for numerous statistical and graphical methods to be used to assess whether the relative risk of VIOXX compared to placebo was constant over time or if it changed over time. The use of the variable, logarithm of time, was an element in the primary method specified. The reference to logarithm of time in the description of methods published in the NEJM was in error. The reference to treatment-by-log (time) interaction should have referred to treatment-by-linear-time interaction. The reported p-value = 0.01 came from that test using linear time, not logarithm of time. Recent tests show that the result using logarithm of time based on the final dataset has a p-value = 0.07. Results of diagnostic analyses indicate that a model using linear time is more representative of the data than one using logarithm of time. Thus, the linear time analysis is an appropriate method to assess the changes in relative risk over time.

As specified in the analysis plan, Merck used additional analytical and graphical methods to evaluate whether the relative risk changed over time. These methods included a Kaplan-Meier plot that showed similar curves for placebo and VIOXX during the first 18 months, which then began to separate at approximately 18 months. Relative risks were also calculated over successive six-month intervals in the study. Over the 36-month period of the study, the relative risk was lowest in the first three sets of six-month intervals and highest in the last three sets of six-month intervals, again demonstrating changing relative risk over time. The results of the linear time analysis, the Kaplan-Meier plot, and the interval relative risks together confirm that the relative risk changes over time. In the APPROVe base study, the increased relative risk was observed beginning after 18 months.

A copy of Merck's letter to the scientific community is available on the VIOXX Information Center at: www.merck.com.

About the APPROVe Study

APPROVe (Adenomatous Polyp Prevention on VIOXX) was a multi-center, randomized, placebo-controlled, double-blind study designed to evaluate the efficacy of 156 weeks (three years) of treatment with VIOXX 25 mg in preventing recurrence of colorectal polyps in patients with a history of colorectal adenomas. There was no Statistical Analysis Plan (SAP) for the cardiovascular data from APPROVe alone. Merck planned to combine the cardiovascular data from APPROVe with data from two other placebo-controlled studies, VICTOR and ViP. Given the decision to stop the study early, the APPROVe data were analyzed separately.

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. For more information, visit www.merck.com.

Forward-Looking Statement 

This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements are based on management's current expectations and involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements. The forward-looking statements may include statements regarding product development, product potential or financial performance. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Merck's business, particularly those mentioned in the cautionary statements in Item 1 of Merck's Form 10-K for the year ended Dec. 31, 2005, and in its periodic reports on Form 10-Q and Form 8-K, which the Company incorporates by reference.