Consumer Group Sues FDA to Release Research Protocol for Banned Diet Drug
Suit Challenges Trade Secrets Provision
WASHINGTON, D.C., Jan. 14, 1998 -- Public Citizen filed suit in federal
court today to force the U.S. Food and Drug Administration to release vital
information about the post-approval testing of the popular diet drug Redux,
which was taken off the market recently after being linked to heart valve
damage that affected thousands of people.
Serious questions about the safety of Redux arose in the fall of 1995 when
FDA's first advisory committee voted not to approve the drug. A second
committee later narrowly approved it by a 6-5 margin but unanimously
insisted that unanswered questions about its safety -- including the
possibility of it causing brain damage -- be addressed in a post-marketing
study.
"The design and results of post-market safety studies must be open to
public scrutiny," said Dr. Sidney Wolfe, MD, director of Public Citizen's
Health Research Group, which opposed the approval of Redux in April 1996.
"The FDA is conspiring with the drug industry to keep this information
secret instead of protecting the public interest by releasing it. The
safety of hundreds of thousands of consumers who have taken a drug takes
precedence over a company's hypothetical arguments about trade secrets."
The lawsuit specifically asks that the FDA be required to release the
research protocol for the Phase IV, or post-marketing safety study, for
dexfenfluramine, known by the trade name Redux. Public Citizen filed the
suit in the U.S. District Court for the District of Columbia after the FDA
failed to act on the group's Aug. 21, 1997, request for the research
protocol under the Freedom of Information Act.
Redux was approved for marketing in April 1996 on the condition that
Wyeth-Ayerst Laboratories of Philadelphia, the drug's U.S. distributor,
conduct a Phase IV study to assess the drug's long-term safety, including
its potential to cause neurotoxicity, or brain damage. Phase IV studies are
routinely conducted when questions remain about a new drug's safety at the
time of approval.
The diet drug was withdrawn after only 17 months on the market because of
its association with heart valve damage and another potentially fatal
condition, primary pulmonary hypertension. Wyeth-Ayerst and the FDA did
not agree to the specific Phase IV study protocol until August 1997, a week
before the Journal of the American Medical Association published a
literature review of studies on the effects of the drug on serotonin levels
in the brains of animals. This was 16 months after the drug was approved
and only one month before it was withdrawn.
The issues surrounding the approval of Redux also raise concerns about the
Phase IV study protocol agreed to by the FDA and Wyeth-Ayerst Laboratories
in August 1997. Drug companies have routinely prevented the FDA from
releasing Phase IV protocols to the public by citing a Freedom of
Information Act provision that prevents disclosure of so-called
confidential commercial information.
The FDA's willingness to agree to Phase IV studies of unknown scientific
validity as the agency has been pressured to approve more new drugs in a
shorter length of time places into serious question whether the drug safety
system adequately protects prescription drug consumers.
Wolfe criticized the secrecy and the amount of control that the FDA allows
drug companies to exercise over the Phase IV process. Phase IV protocols
are negotiated behind closed doors between the drug company and the FDA;
the scientific validity of these protocols is unknown; and the FDA does
not have the authority to ensure that Phase IV studies are completed.
"The FDA's instinct seems to be to put the industry's interests before
those of the public," Wolfe said. "Redux is a perfect case in point. The
drug was approved on the condition
that the manufacturer conduct safety studies once it was on the market. Yet
17 months later -- after millions were exposed, just one month before
recall -- rigorous, scientific studies to evaluate its safety still had not
commenced because the manufacturer would not agree to a study design.
"Public Citizen has a major concern that poorly conceived Phase IV
protocols will not answer important public safety questions and may mislead
doctors and the public into thinking a potentially dangerous drug is safe
when, in fact, it is not," Wolfe said.
Public Citizen recently won an important lawsuit involving a Phase IV
safety study. Public Citizen requested and was denied the Phase IV protocol
for the popular diabetes drug metformin (known commercially as Glucophage)
produced by Bristol-Myers Squibb of Princeton N.J. This drug is associated
with lactic acidosis, an adverse reaction that is fatal approximately 50
percent of the time. In that suit, filed in the U.S. District Court for
the District of Columbia on July 16, 1996, the court found in its Nov. 3,
1997, judgment "that no competitive harm will flow from the release of the
metformin protocol."
REDUX TIMELINE
May 1993 - Interneuron Pharmaceuticals Inc. files a New Drug Application
(NDA) with the Food and Drug Administration.
Dec. 1993 - Neuroscientists write the FDA with their concerns, based on
animal studies, over the possibility of neurotoxicity in humans.
Sept. 1995 - FDA advisory committee votes 5-3 not to recommend approval
because of concerns over primary pulmonary hypertension and possible
neurotoxicity.
Nov. 1995 - In a highly unusual move, the FDA convenes a second advisory
committee, this time voting 6-5 for approval.
Dec. 1995 - Neuroscientists again contact the FDA to express concern about
the drug's potential to cause neurotoxicity in humans.
Apr. 1996 - Public Citizen urges the FDA to delay approval until the
potential for neurotoxicity in humans can be assessed.
Redux is cleared for marketing by the FDA.
Aug. 1996 - The International Primary Pulmonary Hypertension Trial is
published in the New England Journal of Medicine showing that the risk of
primary pulmonary hypertension increases 23 times when Redux or other diet
drugs are used for longer than three months.
July 1997 - Mayo Clinic doctors announce they have identified 24 women who
used diet drugs and developed heart valve damage.
FDA issues Public Health Advisory about heart valve damage.
Aug. 1997 - Wyeth-Ayerst Laboratories announces agreement on the Redux
Phase IV study protocol with the FDA.
A major review of Redux neurotoxicity in animals is published in the
Journal of the American Medical Association.
Mayo Clinic study is published in the New England Journal of Medicine.
Sept. 1997 - Redux is withdrawn from the market.
Larry D. Sasich, Pharm.D., M.P.H., FASHP
Research Analyst
Public Citizen Health Research Group
1600 20th Street, NW
Washington, DC, USA
Phone: 202-588-7782
FAX: 202-588-7796
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