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Consumer Group Sues FDA to Release Research Protocol for Banned Diet Drug

Consumer Group Sues FDA to Release Research Protocol for Banned Diet Drug

 Jan. 14, 1998

Suit Challenges Trade Secrets Provision

WASHINGTON, D.C. — 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 its 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The diet drug was withdrawn after only 17 months on the market because of its association with heart valve damage and another potentially fatal condition, primary pulmonary hypertension.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.”




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.

April 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.