NEWS - Merck & Co. researchers privately sought to reformulate Vioxx in 2000 to reduce its cardiovascular side effects

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By THERESA AGOVINO, AP Business Writer Thu Jun 23, 7:31 AM ET

NEW YORK - Merck & Co. researchers privately sought 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 relief

medication'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.

But behind the scenes, 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 plaintiff

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. The

desire to reformulate the drug suggests a level of urgency that goes beyond

previously disclosed internal e-mails that discussed safety risks.

" The document suggests a level of concern about the drug. The fact that they

wanted to patent a different product raises questions - it says something, "

said Sebok, a professor at Brooklyn Law School. " Should they have

been open about concerns? The failure to be honest is what gets companies

(in product liability cases) in trouble. "

A copy of the document was provided to The Associated Press on the condition

that its source not be identified. A lawyer for Merck declined to discuss

the specifics of the document, contending that it was a privileged internal

company discussion.

" We continue to believe we acted responsibly, " said Merck spokeswoman

.

Merck shares fell 1 cent to $31.98 in trading Wednesday on the

New York Stock Exchange. They have traded in a 52-week range of $25.60 and

$48.42 a share.

According to the document, 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. Such 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 privileged 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.

Zipursky, a professor at Fordham Law School in New York, said it's

conceivable that other judges could rule differently and allow the document

to be used in Vioxx cases. Lawyers in the Texas case said they have the

document and will attempt to make it part of their evidence.

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, , Hubbard & . 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.

Vioxx is one of a class of drugs known as -2 inhibitors that were

originally touted as a super aspirin because they didn't cause ulcers and

other gastrointestinal problems that can be a byproduct of the use of

aspirin, which is cardioprotective.

The statement from Merck's law firm said the application had nothing to do

Merck's firm belief in the cardiovascular safety of Vioxx.

Plaintiff 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.

One such document is a March 9, 2000, e-mail in which Scolnick said he was

concerned that the higher risk of heart attacks and strokes was " mechanism

based. " Plaintiff lawyers contend that was an admission by Scolnick that the

way Vioxx works in the body can contribute to heart troubles.

Rep. Henry A. Waxman (news, bio, voting record), a California Democrat, said

in a report after a review of Merck documents that the company armed over

3,000 sales people " with misleading information about Vioxx's health risk. "

One document disclosed as part of the congressional inquiry indicated that

Merck instructed sales people to show physicians a pamphlet showing Vioxx

might be 8 to 11 times safer than other anti-inflammatory drugs. Another

memo told sales representatives not to bring up the drug's heart risks with

doctors.

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 June 1, 2005, deposition 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. He said his idea

was not a reaction to FitzGerald's theory.

But as Merck pursued the reformulation, it continued to stand by Vioxx's

safety. In a press release dated April 28, 2000, the company " confirmed the

favorable cardiovascular safety profile of Vioxx. "

http://news./s/ap/20050623/ap_on_bi_ge/vioxx_safety;_ylt=AmjGiWuZIo3Swb\

hatHEq45ys0NUE;_ylu=X3oDMTA3czJjNGZoBHNlYwM3NTE

Not an MD

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org