Fen-Phen: Rise and Fall of a Diet Drug By Rosanne Bachman, London A major US Pharmaceutical Co. is weighting in about GBP 2.35 billion (USD 3.75 billion) lighter these days, or at least their bank account is. This was the amount they agreed to in a structured settlement in response to a nationwide class action suit they faced. This settlement came after a USD 6 million settlement in November of 1999 for two women in Texas and more recently another settlement for 5 people in Mississippi in December for USD 150 million. So far that totals a little over USD 3.9 billion in under 6 months for one drug. Wondering what kind of problem they had to cause losses of a size not seen since asbestos and breast implants? You are probably thinking it was a new drug brought to market, but the drug that caused the company to settle a nation wide class action suit for USD 3.75 billion rather than face a US court was a diet drug, fenfluramine, approved by the FDA in 1973. The FDA approved the drug to fight obesity for "single drug, short-term use." This would seem to be how it was administered for quite sometime without event. A New Drug Combination: "Fen-Phen" In 1992, a study was published that showed that by using fenfluramine with another diet drug phentermine, which is an amphetamine-related stimulant, that side effects of dry mouth, drowsiness and in very rare cases pulmonary hypertension for fenfluramine and insomnia and irritability for phentermine could be reduced while maintaining effective weight loss with both drugs being taken at lower doses. However, since the doses were lower, the doctor performing the study lengthened the duration of administering the drugs. A critical note by the FDA at that time of approval for fenfluramine, was that safety of use beyond one year had not been established in clinical trials. The combined administration of fenfluramine and phentermine, a close relation to fenfluramine, became known as Fen-Phen. Phentermine also had a long history behind it, being approved for sale in 1959 by the FDA. Despite the above stated side effects of insomnia and irritability, phentermine also spent its time on the market without event. Then, beginning in September 1997, almost 40 years after phentermine's FDA approval, Fen-Phen's increasing notoriety among lawyers spawned a surge in legal action against not only manufacturers and distributors of phentermine, but also and to a much greater extent the manufacturers and distributors of fenfluramine and dexfenfluramine (known as Redux a derivative of fenfluramine approved in 1996). A Deluge of Lawsuits The lawsuits began within weeks of a July 1997 Mayo Clinic paper being published. The report showed heart valve damage in 1/3rd of those studied who had been taking some combination of the above drugs. By September 1997, hundreds of suits had been filed, 100 in New York alone by one lawyer who was quoted as saying "It is going to be bigger than breast implants" (USD 4.22 billion). Today over 11,000 suits are filed against the company mentioned at the beginning of the story alone! A UK company that had manufactured phentermine for less than one year had 225 suits filed against them, some of them class action suits. Hundreds of companies have been sued over Fen-Phen, a large number of whom are US based, but along with UK companies, European companies have felt the long arm of the US court system. So how does a mega problem as this develop? These additional facts are what a court considers: Remember from above, the FDA approval was for single drug use. That means not in combination with another drug. So there was no FDA approval for the drug used in combination. Also the FDA said that the clinical trials did not cover longer use. The FDA approved the drug for a number of "weeks" of use. A 32-year-old woman who lost 70 pounds was found to have a leaky heart valve after taking Fen-Phen for over a year. In Widespread Use Six million Americans took some Fen-Phen or Redux combination. In just one year, 1996, 18 million prescriptions were written for a Fen-Phen combination. Some of the writers of the prescriptions were diet centers. They have a trained physician on staff but again, these drugs were approved for treatment for a clinical determination of obesity and not simply due to being overweight. With that many prescriptions being written, someone had to notice that these formerly unpopular drugs were now becoming dramatically more popular. The company noted at the beginning of this article had USD 305 million in revenues from fenfluramine in 1996. One company saw a USD 20-million-drop in the sale of their phentermine product when fenfluramine and Redux were voluntarily removed from the market in September of 1997. The warning labels did not warn about coadministration with other diet drugs. There were allegations the sales people for the drug companies promoted the use of their drug in combination. At least one person died who took the drugs. Warnings from Europe The FDA requires any drug company to report any serious and/or unexpected adverse effect no matter where the effects occur if they appear related to the drug. A doctor in Belgium had done a study in 1994 that showed leaky heart valves from fenfluramine used in Belgium. The drug came from a French manufacturer who licensed the drug to the US manufacturer involved in the settlements. The French company alleges to have told the US company of the study and, in fact, the pharmaceutical company passed on SOME of the reports to the FDA but not all. They stated later that they did not think the reports were relevant because the Belgians studied were also taking Chinese herbs which they felt were the cause of the leaky heart valves. It is interesting to note that even in their original clinical trials, there were rare cases of pulmonary hypertension (heart problems,) but these trials were for less than one year. Fenfluramine and dexfenfluramine were voluntarily removed from the market in September of 1997, but phentermine remains available. Armed with this information, plaintiff attorneys now make numerous allegations adverse to the pharmaceutical company. A company who, without encouraging combined use of their drug, turns a blind eye to the massive revenues it generates. This sales explosion also calls into question whether they diligently enforced the proper use of the drug as a treatment for obesity, not merely due to being overweight. Further, consumers were not warned of the possible risks of both combining the drug with other medications and using it for an extended period of time. Finally, when the manufacturer was notified in 1994 of the studies in Belgium, they appeared less than forthright in their efforts to share all the findings with the FDA. Consumers might also assert that the pharmaceutical company would have the responsibility to warn them of side effects especially when used in combination with other drugs. The 6 million people who were told they had a safe easy way to lose weight who now will have to wonder for years if they too will develop heart problems. The main problem, however, is the people who already show heart damage like the 32-year-old woman with a leaky heart valve, who says if she had known about the risks she never would have taken the drugs. Unfortunately, she didn't have the opportunity to make that decision. Where We Go From Here Hypothetical accusations aside, some people may think that those who took these drugs were just looking for the easy way out. They should have known that it was too easy and that there could have been a downside, that some of the responsibility lies with them. In fact, some recent studies say the drug combination isn't the cause of the heart problems or after some time of discontinued use the problem subsides. No one really knows for sure yet. What is known, however, is that some people have problems and one thing these people have in common is Fen-Phen. Thus, although it is possible that many people who also took Fen-Phen might develop similar problems, perhaps they will not. Either way, additional studies may be called for to determine whether Fen-Phen is the true cause of the problems claimed by the individual plaintiffs. 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