Friday, June 24, 2005

Did Merck try to change Vioxx in 2000?

From various sources, including

Merck researchers tried to reformulate Vioxx in 2000 to reduce its cardiovascular side effects, even as the drug maker was publicly playing down a study that highlighted the pain reliever's potential heart attack risk, an internal company document shows.

The widely publicized study in March 2000 found that patients taking Vioxx were five times more likely to have heart attacks than individuals using the generic medicine naproxen. Merck insisted at the time that this was a result of naproxen's cardioprotective properties and not any defect in Vioxx.

Company scientists were considering combining Vioxx with another agent to reduce the risk of heart attacks and strokes, according to a document that was mistakenly provided by Merck to plaintiffs lawyers as part of the evidence-gathering process in one of the hundreds of Vioxx lawsuits around the country.

That document, a communication between Merck researchers and the company's patent department, stated that the way Vioxx works to reduce pain might also increase cardiovascular problems. They suggested a patent be sought for a combination drug mixing Vioxx with another agent to lessen the risk.

Merck removed Vioxx from the market last September after a later study showed it doubled patients' risk of heart attacks and strokes. Thousand of wrongful death and injury lawsuits have been filed against Merck based on claims that the company hid Vioxx's risks. Analysts estimate the company's liability could reach as high as $18 billion. The first trial is set to begin next month in Angleton, Texas.

The document is potentially among the most damaging to emerge since the drug's sales were suspended because it calls into question the bedrock Merck defense that company officials were convinced of the drug's safety.

According to the document, Edward Scolnick, the former head of Merck's research labs, was the first to suggest combining Vioxx with an agent that would block blood platelets from clotting. Clots can lead to heart attacks and strokes. There are three dates on the document; the first is March 30, 2000.

The document's authors said Vioxx might reduce the production of a substance called prostacyclin, which prevents platelet aggregation. That reduction may alter the ratio of prostacyclin to thromboxane, a substance which can constrict blood vessels and cause clotting. The change may cause increased risk of cardiac and cerebral adverse events, the document said.

The document became an issue in a New Jersey Vioxx lawsuit when Merck objected to its use on the grounds that it was an attorney-client communication between company scientists and in-house patent counsel.

New Jersey Superior Court Judge Carol E. Higbee ruled May 27 that the document was privileged and could not be used at trial. She also ordered that all copies of the document be returned to Merck or destroyed, but she required Merck to turn over other documents related to the reformulation, including e-mails and memos, within 30 days.

Merck filed an application with the U.S Patent Office in 2001 to combine Vioxx with what is called a thromboxane inhibitor, according to a statement released Wednesday by the company's counsel, Hughes, Hubbard & Reed. The statement said the hope was that Vioxx could provide cardioprotective protection while preserving its gastrointestinal benefits. But the project was later dropped, making the patent application moot.

Plaintiffs lawyers say other documents call into question Merck's assertion that it acted responsibly and in the best interest of patients at all times, including pulling the drug when it had evidence of potential harm. Merck counters that the documents have been taken out of context.

The prostacyclin theory was first advanced in 1998 by Dr. Garret FitzGerald, a prominent cardiologist who said Merck did not embrace it. However, FitzGerald said that after the 2000 study was released, Merck executives called him to discuss the issue.

In a deposition earlier this month on the Vioxx case, Scolnick said that Merck did work on the reformulation because it knew Vioxx would have to carry some type of a warning about cardiovascular risk on its label.