By Kathryn Calkins,
Steve Usdin
& Mike Ward

Now that it has pulled Redux dexfenfluramine and Pondimin fenfluramine from the U.S. market, Wyeth-Ayerst Laboratories must brace for litigation. One protection that the pharma company could raise is a well-performed epidemiological study demonstrating no statistical link between taking the drugs and developing heart valve defects. But while such a study could bolster the company's position in court, product liability attorneys contacted by BioCentury suggest it does not offer a watertight defense.

The company's ability to conduct a definitive epidemiological study is already hampered by the drugs' removal from the market. The company cannot conduct a prospective trial of patients before and after they begin drug use. Instead, Wyeth-Ayerst will begin enrolling a study within two weeks that compares obese patients who took the drugs with those who never took them.

The company will enroll 400 who took Interneuron Pharmaceuticals Inc.'s Redux and 400 who took Fen-Phen and compare them to an age, weight and sex matched control group of 400 non-users. Echocardiograms will be taken to determine whether heart valve defects disappear after patients discontinue drug use.

Heidi Connolly, a Mayo Clinic physician who conducted the study that first suggested an association between the weight loss drugs and heart valve defects, said that prompt use of the echocardiogram still should reveal any defects related to drug use.

She acknowledged that although the study will provide evidence of a relationship one way or the other, "you could never do the study you need to do now because the drugs are no longer available."

The devil in the details

Ken Fujioka, director of the Nutrition and Metabolic Research Center at Scripps Clinic (San Diego, Calif.), conducts clinical trials in obese patients. He suggested that if Wyeth-Ayerst wants to achieve the least ambiguous result possible, it must carefully match patients in its groups for specific conditions that could skew the incidence of heart valve defects.