Merck Considered Reformulation of Vioxx To Address Safety Risks Three Years Before Market Withdrawal
Three years before Merck voluntarily withdrew the COX-2 inhibitor Vioxx from the market because of concerns over cardiovascular risks, the company applied for a patent on a reformulation of Vioxx that sought to reduce cardiovascular side effects, according to internal company documents, the AP/Long Island Newsday reports. Merck removed Vioxx from the market in September 2004 after a study found that the drug doubled patients' risk of heart attacks and strokes.
The company now faces thousands of wrongful death and injury lawsuits related to Vioxx, and analysts estimate that Merck's liability related to Vioxx could reach as much as $18 billion. The first trial over Vioxx is scheduled to begin in July in Texas. Merck has argued that company officials were confident that the drug was safe prior to the release of the study last year (Agovino, AP/Long Island Newsday, 6/22).
However, in an internal document titled "Confidential Memorandum of Invention" that company executives sent to Merck patent lawyers in March 2000, the company said that Vioxx's mechanism for reducing pain also might increase the risk of cardiovascular problems (Ginsberg, Philadelphia Inquirer, 6/23). The document said that Vioxx might reduce the production of prostacyclin, a substance that prevents aggregation of platelets. The memo continued that the reduction of the substance might change the body's ratio of prostacyclin to thromboxane, which helps constrict blood vessels and can cause clotting, and added that the result might be increased risk of cardiac and cerebral adverse events.
The memo "became an issue" in a New Jersey Vioxx lawsuit after Merck lawyers "mistakenly provided" it to plaintiff lawyers as part of the evidence-gathering process, the AP/Newsday reports. A copy of the document was provided anonymously to the Associated Press (AP/Long Island Newsday, 6/22). In the memo, the executives said that Merck might want to seek a patent for a method of combining Vioxx with another medication to possibly lessen cardiovascular risks.
In March 2001, Merck filed a patent application for a combination of Vioxx with a thromboxane synthase inhibitor, which helps protect against cardiovascular problems caused by blood clots. The application said, "The present invention concerns a method for treating patients with COX-2-mediated conditions and who are also at risk of developing thromboembolic events ... For patients who are taking COX-2 selective inhibitors and who may benefit from the cardiovascular protective effect of aspirin, there remains a need for a cardiovascular protective treatment that does not expose them to increased risk for gastrointestinal side effects."
The application did not "explicitly blame" Vioxx for blood clots but instead said that patients at risk for developing clots would not have the benefit of aspirin's cardiovascular protective effects if they took Vioxx alone, the Inquirer reports. The application also mentioned all COX-2 inhibitors and "aspirin-like compounds" without limiting its discussion to Vioxx, according to the Inquirer (Philadelphia Inquirer, 6/23).
According to the AP/Newsday, the project to supplement Vioxx with a thromboxane synthase inhibitor ultimately was dropped, so the application became "moot" (AP/Long Island Newsday, 6/22). Garret Fitzgerald, a University of Pennsylvania scientist who has studied Vioxx for Merck, said the idea proposed in the patent application was almost exactly the same as a solution he proposed privately to Merck in 2000 (Philadelphia Inquirer, 6/23).
According to the AP/Newsday, the memo "is potentially among the most damaging" documents to emerge since sales of Vioxx were suspended because it "calls into question the bedrock Merck defense that company officials were convinced of the drug's safety" (AP/Long Island Newsday, 6/22).
Plaintiffs' lawyers said that the memo shows that Merck executives "sought the invention to counter Vioxx's tendency to cause blood clots," the Inquirer reports. They added that the memo proves Merck was aware that Vioxx could cause heart attacks and strokes (Philadelphia Inquirer, 6/23). According to the AP/Newsday, the lawyers also said other Merck documents call into question the company's actions.
For example, they cited an e-mail dated March 9, 2000, that they said showed that Edward Scolnick, former director of Merck's research laboratories, was concerned that the higher risk of heart attacks and strokes for Vioxx was "mechanism based." In a June 2005 deposition in a Vioxx case, Scolnick said Merck launched the reformulation project because it was aware that Vioxx would be required to carry a warning on its label.
According to the AP/Newsday, at about the same time the memo was sent, Merck was "playing down a study" published in March 2000 that found patients taking Vioxx were "five times more likely to have heart attacks than individuals using the generic medicine naproxen." At the time, Merck said that the demonstrated increased risk resulted from naproxen's cardiovascular protective effects and not problems related to Vioxx.
In a press release dated April 28, 2000, Merck said the company "confirmed the favorable cardiovascular safety profile of Vioxx" (AP/Long Island Newsday, 6/22).
Merck on Wednesday "denied the allegations, ... saying it recalled Vioxx as soon as reliable studies proved a conclusive link to heart attacks and strokes," the Inquirer reports.
Merck attorneys said that the patent application filed in 2001 shows only that the company sought to help Vioxx users who had switched from aspirin, which helps prevent heart attacks by acting as a blood thinner. "This patent application has nothing to do with Merck's firm belief in the cardiovascular safety of Vioxx," Kent Jarrell, a spokesperson for Merck's outside law firm Hughes Hubbard & Reed, said (Philadelphia Inquirer, 6/23).
Merck spokesperson Cynthia Smith added, "We continue to believe we acted responsibly."
Merck, which mistakenly released the memo to plaintiffs' lawyers, objected to the use of the document in court. The company said the memo was an attorney-client communication between Merck researchers and in-house patent counsel.
On May 27, New Jersey Superior Court Judge Carol Higbee ruled that the document was privileged and could not be used during the trial. Higbee also said that all copies of the document must be returned to Merck or destroyed (AP/Long Island Newsday, 6/23). However, she added, "The court recognizes this is a serious and important point of contention. Merck is ordered to produce any and all information regarding the invention that is not otherwise privileged" (Philadelphia Inquirer, 6/23).
According to the AP/Newsday, other judges could rule differently on the memo and allow it to be used in Vioxx cases. Lawyers in the Texas case scheduled to begin next month said they have the memo and will seek to introduce it as evidence (AP/Long Island Newsday, 6/22).