Healthy Skepticism Library item: 1696

Warning: This library includes all items relevant to health product marketing that we are aware of regardless of quality. Often we do not agree with all or part of the contents.

Publication type: news

Agovino T.
Merck Tried to Alter Vioxx in 2000
Associated Press 2005 Jun 23

Abstract:

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.

Keywords:
Vioxx Merck cardioprotective prostacyclin thromboxane heart stroke Cox-2

Notes:

Ralph Faggotter’s Comments: An embarrassing accidental leak, by Merck, of an internal memo suggests that the company was made aware of a possible mechanism whereby Vioxx could have an increased thrombotic risk as early as March 2000. Rather than telling the world about this possibility, Merck chose to keep this secret and instead began to work on developing a new pill in which Vioxx was combined with an anti-thrombotic agent.How many other similarly interesting secrets would we discover if all drug company archives were opened up?

Full text:

AP: Merck Tried to Alter Vioxx in 2000
By THERESA AGOVINO, AP Business Writer
San Francisco Chronicle
Thursday, June 23, 2005

(06-23) 04:31 PDT New York (AP) —

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 Anthony 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
Cynthia Smith.

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, 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. 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.

Benjamin 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, 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.

Vioxx is one of a class of drugs known as Cox-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, 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.”

Healthy Skepticism Library item: 1696

Announcements