Yourlawyer.com (Fen Phen News) http://www.yourlawyer.com/topics/overview/fen_phen Sat, 21 Nov 2009 12:27:11 -0800 pixel-app en Fen-Phen Damage Long-Lasting http://www.yourlawyer.com/articles/read/15460 Thu, 06 Nov 2008 00:00:00 -0800 http://www.yourlawyer.com/articles/read/15460 Fen-Phen, may continue to damage the heart years after a patient stops taking it, according to a study published online today in BMC Medicine.  The study has shown  that people who stopped using Fen-Phen eleven years ago had damaged heart valves up to seven years later.

The study, conducted by researchers at the Central Utah Clinic, involved both fenfluramine and dexfenfluramine, another diet drug that is closely related to fenfluramine.  The Food & Drug Administration (FDA)  ordered fenfluramine and dexfenfluramine off the market in September 1997 after those drugs were linked to heart valve problems. Since its withdrawal, tens of thousands of lawsuits have been filed against the maker of fenfluramine by people injured by the drug.

This is the largest study to examine duration of exposure to the drug and the first to estimate the incidence of heart valve surgery among prior users. The researchers looked at 5,743 former users of fenfluramine and/or dexfenfluramine.  The patients were seen by doctors at the Central Utah Clinic between July 1997 and February 2004.  Each patient got an echocardiogram and 1,020 patients got two or more echocardiograms 30 months apart, on average.

When the study started, nearly 20% of the women and almost 12% of the men had at least mild regurgitation through the aortic valve or moderate regurgitation through the mitral valve.  Women, and people  who used the drugs the longest were most likely to have such problems.

Follow-up echocardiograms showed that aortic and mitral regurgitation usually stayed about the same or worsened, but improved in some cases. Thirty-eight patients -- less than 1% -- got heart valve surgery. Such surgery wasn't common, but it was more common than in the general public, and in 25 cases, heart valve damage was linked to the drugs.

"We found clear evidence for a strong, graded association between duration of exposure to fenfluramines and prevalence of aortic regurgitation and for mild or greater mitral and tricuspid regurgitation," lead researcher Charles Dahl, told Science Daily.  

]]> Fen-Phen Decision Affirmed by New York Supreme Court http://www.yourlawyer.com/articles/read/13795 Fri, 01 Feb 2008 00:00:00 -0800 http://www.yourlawyer.com/articles/read/13795 Parker Waichman Alonso LLP, to intervene and seek disclosure of documents related to a November 2001 fen-phen settlement.  Last March, New York Supreme Court Justice Charles E. Ramos had ordered a new trial in the so-called “New York Diet Drug Litigation” case.  Parker Waichman had alleged that Napoli, Kaiser & Bern, LLP,  the firm  that negotiated a massive settlement with the maker of the banned diet drug fen-phen,  violated ethical rules by apportioning the settlement in a manner that favored Napoli’s own clients and  inflated its own share of the settlement.   Parker Waichman had referred hundreds of its fen-phen clients to Napoli.

In 2001, Napoli Kaiser & Bern, LLP (now known as Napoli Bern Ripka) sued American Home Products, now known as Wyeth, on behalf of thousands of former  fen-phen users.  The diet drug fen-phen had been recalled by the Food and Drug Administration after studies linked it to heart valve damage.  American Home settled the suit under confidential terms, though the settlement has been estimated to be over $1 billion.

But in a decision issued last March, Judge Ramose wrote that there were serious questions about the way Napoli distributed the settlement among the fen-phen clients.  One of the major points of contention in the New York Diet Drug Litigation was whether or not the fen-phen settlement was an aggregate settlement, whereby American Home Products would pay a lump sum to be divided among numerous plaintiffs.  Because such a settlement puts clients in competition with each other, a settlement law firm like Napoli has a duty to inform its clients of its implications.

Napoli had argued that the fen-phen settlement was not an aggregate settlement, noting that it had been reviewed by Professor Bruce Green of Fordham University School of Law and former Manhattan Supreme Court Justice Michael Dontzin, who served as special master to oversee the settlement.  But in his opinion, Judge Ramos wrote that it was unclear if Napoli had been completely truthful with Green and that it did not appear that the Special Master had actually examined each individual settlement offer or had just examined a random sample for fairness.

In his opinion, Judge Ramos also wrote that it appeared that Napoli had not disclosed the exact aggregate nature of the settlement to clients.  A former lawyer at Napoli, Stephen David Murakami, who had worked on the fen-phen case said in an affidavit that Napoli had told clients their portions of the settlement had been individually negotiated with American Home, when in fact they had been solely determined by Napoli.    According to Murakami’s affidavit, Napoli allegedly inflated the settlement payments of its direct clients because its fees from those clients would not be reduced by referral fees. The vast majority of Napoli’s fen-phen clients were referred by other firms.  

Judge Ramos ruled in his March opinion that he ethical questions posed by the “New York Diet Drug Litigation” could only be addressed in a new trial.

In yesterday’s affirmation, the New York Supreme Court said Judge Ramos properly allowed Parker Waichman, as well as a group of its clients, to intervene and seek disclosure of documents previously under seal relating to the fen-phen settlement.  If disclosed at trial, those documents could reveal exactly how Napoli determined settlement amounts for each fen-phen client, and whether or not the firm committed serious ethical violations in doing so.

]]> Woman's Death Highlights Risk of Herbal Diet Products http://www.yourlawyer.com/articles/read/10512 Mon, 15 Aug 2005 00:00:00 -0700 http://www.yourlawyer.com/articles/read/10512
A 53-year-old woman has died and hundreds of others may be risking their lives by turning to herbal diet products that contain unsafe western medical ingredients, the Department of Health has warned.

The woman died recently after using herbal health products found to contain the substances fenfluramine and propranolol.

Philippa Yu, executive officer of the Hong Kong Eating Disorders Association (HEDA), echoed the warning, saying the need to be slim has spiralled out of control in Hong Kong.

Dr Lo Kwok-wing, a member of the Hong Kong Society of Obesity, says it is hard to predict how many more dieters will fall victim to the remedies.

In addition to the death of the 53year-old woman, hundreds more may have fallen ill over the years and the numbers could soar, Lo warned.

The products are seen as a quick fix solution to dieters unwilling to lose weight the right way - exercising regularly and eating properly.

Natural or herbal health foods are not subject to the Pharmacy and Poisons Ordinance or the Chinese Medicine ordinance, which restrict the sale of drugs.

The herbal dietary products are considered to be health foods and no pre-market approval is required.

It is only when the Department of Health receives information from the general public that products are tested.

``The government needs to maintain a balance between market and public health,'' said Yu. ``I don't think the government has enough experience or policies to control the problem [of Western medicines mixed in herbal slimming products].''

Raymond Ho, representative of the engineering functional constituency of the Legislative Council, said while it is not possible to test all the health foods before they come into the SAR, ``selective testing of products from specific places could help.''

Ho also suggested collaboration between governments would help. ``We can't rely on our own government, we do not have enough resources and have to maintain close communication with other governments, including China,'' he said.

Legco passed an amendment to the Undesirable Medical Advertisements Bill last June that prohibits or restricts advertising claims of herbal or health foods which must also state the ingredients on the labels. The products are not tested before they reach Hong Kong and the government has to rely on the manufacturers to be truthful.

RS Slim & Fit, Trim Up Plus Birds Nest and other health foods have already been yanked off the shelves and banned by the Department of Health.

Fenfluramine was banned in the United States in 1997 after being linked to several deaths. Western dietary drugs can only be prescribed by doctors and are usually used to treat severe obesity.

The case of the unnamed woman who died is still being investigated. There is no English name for the product she consumed, believed to have contained fenfluramine, which is often mixed with phentermine.

The ``fen-phen'' craze in the US led to more than 50,000 product liability lawsuits filed by alleged victims.

In Hong Kong, fenfluramine was deregistered in 1998 after being linked to heart-valve disease. But slimming aids containing the drug can still be found in the territory and other parts of the world, according to health experts.

In a survey conducted by the Hong Kong Eating Disorder Association in 2003, 60 percent of 1,200 women of all ages surveyed in the SAR were considered normal weight, yet 90 percent of them said they had tried slimming products.

With increasing trade flows between Hong Kong and China, authorities are finding it difficult to control the banned products although importers, wholesalers and retailers selling unregistered pharmaceuticals face a fine up to HK$100,000 and two years in prison.

Since 2003, only 26 herbal slimming products, containing Western medicines, have been recalled.

Herbal slimming products containing Sibutramine, also known as Meridia, an appetite suppressant that causes increases in blood pressure and heart rate, are among the latest products banned in the SAR. Sibutramine was the first appetite suppressant to receive approval by the United States Food and Drug Administration after the fenfluramine ban. In 2002, 29 deaths were linked to the drug since its launch in 1998. Italy banned it in 2002 and withdrew all products that contained the ingredient after receiving 50 reports of health-related problems linked to the drug.

According to Public Citizen, a consumer advocacy group which petitioned to ban Sibutramine in the US, 19 of the deaths were caused by adverse cardiovascular effects in users of the drug. Abbott Laboratories, which produces the drug, continues to stand behind it.

In Hong Kong this year, five of the eight slimming drugs banned by the Department of Health contained Sibutramine.

In the Consumer Council survey on health foods released Monday, five percent of respondents reported side effects such as diarrhoea, insomnia, lassitude, dizziness, sweating and thirst. Some side effects were attributed to slimming or herbal tea products.

An analysis of 80 health food product labels found most of them gave no information on contra-indications and side effects.

The number of proprietary Chinese medicine samples for treatment of obesity sent to the government laboratory increased sixfold over 2003, according to a Hong Kong government laboratory report last year.]]> $1.013 Billion Award In Wyeth 'Fen-Phen' Case http://www.yourlawyer.com/articles/read/7969 Wed, 28 Apr 2004 00:00:00 -0700 http://www.yourlawyer.com/articles/read/7969
Cynthia Cappel-Coffey, 41, took the drug Pondimin between November 1996 and June 1997. In December 2001, she developed a fatal lung condition called primary pulmonary hypertension. She died last year.

Yesterday's verdict, which Wyeth said it would appeal and which financial analysts predicted would not stand, adds to the legal costs stemming from the diet drugs that the Madison, N.J., company pulled from the market in 1997 after some users developed heart-valve damage.

Wyeth has set aside $16.6 billion to resolve lawsuits by former fen-phen users. It reached a class-action settlement in 2000 for $3.75 billion with more than 125,000 former users of the diet drugs. An additional 70,000 fen-phen users opted out of the settlement to take their cases to trial.

Most of the remaining cases allege heart-valve damage as a result of the drugs. The PPH cases represent only a fraction of 1 percent of the cases in its diet-drug litigation, Wyeth said.

The verdict yesterday was the first PPH case to go to trial. The company has settled all other PPH cases out of court. Wyeth warned investors in its first-quarter earnings call last week that it had been unable to settle the Texas case - and that it might have to take future charges to settle costly litigation.

Jurors deliberated six days before awarding Cappel-Coffey's family $113 million in compensatory damages and $900 million in punitive damages. The family had asked for $1.1 billion in total damages.

Wyeth officials expressed optimism that the verdict would be reversed.

"The case is full of legal and factual errors," said Tim Atkeson, one of Wyeth's trial attorneys in Texas. "We are quite confident that the verdict is going to get reversed."

Elizabeth Bernstein, an analyst with Morningstar Inc., in Chicago, who covers Wyeth, called the $900 million punitive-damages award "absurd. I don't see how this would not be lowered, either by the trial judge or on appeal. I don't think it will stand."

Bernstein said that of the 70,000 fen-phen users who opted out of the class-action settlement, only about 3 percent have had their claims approved, with an average settlement of $125,000 each. "Wyeth can withstand a considerable amount of litigation charges," she said. "While I don't think it will stand at this level of $900 million, if it were to stand, and other cases were to appear, it would cause liquidity problems for Wyeth."

Bernstein said she expected Wyeth to take an additional $2 billion charge this year to cover ongoing litigation expenses related to fen-phen.

Wyeth's attorneys argued during the trial that Cappel-Coffey stopped taking the drug in June 1997, and did not get sick until 41/2 years later, in 2001, and that if Pondimin had caused her death, she would have become ill within the first year.

Wyeth, which employs 4,700 people in the Philadelphia area, said yesterday that the court had prevented the company from submitting evidence about three other diet drugs the woman took after Pondimin, including two that carried label warnings of possible PPH damage.

Texas law limits punitive damages at two times lost wages, medical expenses, and lost services. In Cappel-Coffey's case, those losses amounted to $1.5 million, which when doubled would have been $3 million, Atkeson said.

But the Texas district judge let the case go to the jury without a limit on punitive damages after the woman's family attorney argued that a felony was committed because documents had been destroyed in the case.

"We are quite confident that a court of appeals will find this was not a felony and that the jury applied the wrong law and that the evidence did not back up the finding," Atkeson said.

Hemant Shah, an independent pharmaceutical analyst in Warren, N.J., said the verdict was a "significant negative" for Wyeth and would make it "very difficult for future PPH cases to be settled. Wyeth has not made public how many PPH cases are pending, but if any large judgment is sustained on appeal, it's going to make it very difficult for Wyeth to settle any outstanding future PPH cases," Shah said.

Wyeth spokesman Doug Petkus said yesterday that "a handful of other PPH cases remain" and that the company said evidence admitted in the Texas case "has already been ruled inadmissible in the heart-valve cases in federal court in Philadelphia."

"Another big potential cloud hanging over the company, which is totally ignored by the financial community," said analyst Shah, is future possible litigation concerning Wyeth's hormone-replacement therapies, Prempro and Premarin. The female hormone drugs, used by millions of women to treat menopausal conditions, have been linked in studies to increased risk of heart disease and stroke in some women.

Morningstar analyst Bernstein said she did not see litigation over hormone-replacement treatments as a big threat.

"It's too hard to prove increased risk of stroke, specifically because of the drug," she said. "There are so many other things that cause stroke and heart attack. It's just a much more difficult case to make. It's a risk. I don't see it as a likelihood to the extent of fen-phen."]]> Fen-Phen Federal Lawsuit Filed for Miss., Tenn. Residents http://www.yourlawyer.com/articles/read/7925 Mon, 19 Apr 2004 00:00:00 -0700 http://www.yourlawyer.com/articles/read/7925
The lawsuit was filed on behalf of 600 people, residents of both Mississippi and Tennessee. The plaintiffs claim they have suffered heart disease from using the diet drugs, but say the medical condition remained undetected until they had test performed after September 20th, 1999.

That's two years after the drugs were removed from the market.

The plaintiffs are seeking unspecified damages from American Home Products in the suit filed in Greenville, Mississippi.

]]> Woman Wins Fen-Phen Suit http://www.yourlawyer.com/articles/read/6949 Fri, 07 Nov 2003 00:00:00 -0800 http://www.yourlawyer.com/articles/read/6949
Jurors awarded Deborah Hayes $810,000 for future medical expenses and $500,000 for future mental anguish.

Hayes, 46, sued Fen-Phen maker Wyeth-Ayerst Laboratories (WYE), claiming the combination of the drugs damaged a valve in her heart. The postal worker said she took Fen-Phen for 90 days over a six-month period in 1999.

Doctors found plaque in her heart valve, a condition usually found in the elderly, her defense attorney, Jim Morris Jr., told the Beaumont Enterprise.

A Dallas lawyer representing Wyeth, said he would ask state District Judge Gary Sanderson to negate the future medical expenses award. He also said the award will be appealed to the Texas Ninth Court of Appeals, and if necessary, the Texas Supreme Court.

Hayes opted out of a pending class action suit against Wyeth. The St. Davids, Pa.-based company faces about 70,000 similar opt-out lawsuits.

Wyeth has set aside $16.6 billion for Fen-Phen settlements, including $2 billion this year.]]> 'Fen-phen' Users Say Records Held http://www.yourlawyer.com/articles/read/5803 Fri, 02 May 2003 00:00:00 -0700 http://www.yourlawyer.com/articles/read/5803
Patients who have heart conditions as a result of taking the once-popular mix are eligible for compensation under a national settlement agreement. But they need medical records to prove their cases.

The deadline to submit some of the medical paperwork is Saturday, which has patients like Delores Hall, 53, of Costa Mesa, scrambling.

Hall said she received fen-phen from 1996 to 1997 from Dr. Kenneth LaCroix, but he hasn't responded to her requests for medical records. LaCroix's office phone has been disconnected, and he could not be reached for commenT.]]> Shirley Scott, 67, a Phila. Native and 'Queen of the Organ' http://www.yourlawyer.com/articles/read/631 Tue, 12 Mar 2002 00:00:00 -0800 http://www.yourlawyer.com/articles/read/631
Though she spent decades as one of the most visible and beloved members of the Philadelphia jazz community, Ms. Scott, who lived in West Chester, made headlines most recently as a litigant.

In February 2000, she won an $8 million settlement against American Home Products, manufacturers of the now-banned diet drug fen-phen, and the doctor who prescribed it to her. Ms. Scott began taking the drug "cocktail" in 1995, and by 1997 had developed primary pulmonary hypertension that forced her to be hooked up to an oxygen tank 24 hours a day.

Ms. Scott came to prominence in the late '50s, when groups built around the Hammond B3 organ were a hot sound in jazz. She got her break with Eddie "Lockjaw" Davis, but in 1960 married another saxophonist, Stanley Turrentine. During their 11-year union, the couple had three children and made some of the most influential records in soul-jazz.

Ms. Scott was neither a speed demon nor a show-off. Rather than unleash a barrage of notes, she toyed fancifully with motifs and melodies - even her heated improvisations had a breezy air.

While most groups anchored by the B3 leaned on blues, Ms. Scott and her cohorts sought out obscure show tunes and standards as well as pop songs, such as the Beatles' "Can't Buy Me Love." Another trait that distinguished Ms. Scott was her low-key approach to accompaniment. With chordal jabs and darting two- or three-note quips, she gently prodded soloists into unexplored territory.

"She really listened," said tenor saxophonist Larry McKenna, who worked with her at Ortlieb's Jazz Haus in Northern Liberties. "She always focused in on what you were playing."

"She knew how to complement a soloist," said Mickey Roker, Ms. Scott's drummer for many years. He added she was one of few organists who could maintain a serious swing pulse on the keyboard while pumping out bass lines on the foot pedals.

Beginning in 1958 with Great Scott! on the Prestige label, Ms. Scott recorded more than 50 albums as a leader, and performed with saxophonist Dexter Gordon, trombonist Al Grey, and others. She switched to piano in the '80s, and recorded on the organ only sporadically after that. Her last album was 1996's Walkin' Thing.

Ms. Scott began teaching jazz history and piano at Cheyney (Pa.) University in 1991, and two years later took another leap, serving as musical director for Bill Cosby's quiz show You Bet Your Life, taped in Philadelphia.

Ms. Scott grew up in North Philadelphia and played trumpet at Philadelphia High School for Girls. But as a senior, she ran away with a touring band to play piano. It was a mistake, she would recall: "A week later the fellow who had the band called my mother and she came and got me."

The incident did not deter Ms. Scott. When "Lockjaw" Davis came to town in 1953, he combed the city for an organ player until he discovered Ms. Scott. She recorded with the saxophonist often, and backed him on 1958's In the Kitchen - one of several classics in Ms. Scott's discography that have been sampled by acid-jazz producers. ]]> Fen-phen maker agrees to $3.75 billion settlement http://www.yourlawyer.com/articles/read/46 Fri, 08 Oct 1999 00:00:00 -0700 http://www.yourlawyer.com/articles/read/46
"Settling this matter was in the best interest of those who used Pondimin or Redux as well as of the company," said AHP President and Chief Executive Officer John R. Stafford. "We believe that this agreement is a sound way to resolve the claims raised by diet drug users and represents a prudent course for our company. It offers peace of mind to those who used the drugs and permits the company to move beyond the uncertainty and distractions of litigation."

Under the settlement, which is subject to court approval, AHP does not admit to any wrongdoing.
When doctors started prescribing Redux and Pondimin, which made up the fen-phen combination, it seemed like the answer to millions of Americans' weight-loss prayers. The drug combination melted away pounds.

But in July 1997, researchers at the Mayo Clinic issued a startling report linking heart valve disease with patients who took fen-phen.

As a result, Wyeth-Ayerst Laboratories, the pharmaceutical division of AHP, withdrew fenfluramine (Pondimin) from the market. Later in the year, the Food and Drug Administration advised those who took the drug combination to see their doctors.

Many doctors feared that perhaps millions of people who took fen-phen would develop heart problems, but those fears were unrealized.

Earlier this year, in the largest study of its kind, researchers attempted to pinpoint who was at risk for heart valve disease as a result of taking fen-phen.

The study concluded those who took the diet drug combination for less than six months did not develop heart valve disease any more often than those who never took the drug.

However, researchers found those who took fen-phen for more than two years had a 17 percent increased risk of developing heart valve disease.

Still, the controversy hasn't ended. Last week, a group of Boston researchers published a study concluding fen-phen has no role in causing heart valve disease, regardless of the length of time a person takes it. ]]> American Home Seeks Settlement http://www.yourlawyer.com/articles/read/1187 Tue, 28 Sep 1999 00:00:00 -0700 http://www.yourlawyer.com/articles/read/1187
Part of the reason the sum is so big is the sheer number of people involved. Six million Americans took Pondimin, the "fen" in the fen-phen cocktail, or its chemical cousin Redux before American Home Products withdrew them two years ago amid links to heart-valve disease.

But American Home may also be interested in reaching a settlement because its strategic position has eroded in recent weeks. For one thing, the Federal Bureau of Investigation has begun, in a preliminary way, to look into Redux's 1996 approval by the U.S. Food and Drug Administration; any new revelations could hurt American Home's defenses in civil trials. The company says that it isn't aware of any FBI inquiry and that all its actions with respect to diet drugs have been lawful.

First Verdict

More important, the first of 4,000-plus diet-drug lawsuits to reach a verdict went badly for American Home last month. In Canton, Texas, a jury voted to award $23.4 million to Debbie Lovett, who developed heart-valve leaks after she took fen-phen.

The case was settled for less, but the evidence presented revealed a record of monitoring patient safety that struck some jurors as callous. "They were looking at the dollars and at how to please their stockholders, and not at how to protect the public," says one, Ronnie Wilson Jones.

The proposed $4 billion settlement would affect only litigation involving heart-valve damage. American Home would still face suits based on primary pulmonary hypertension, a rare but often-fatal lung disease also associated with the drugs. Further complicating the picture: Monday a judge rejected a proposed $100 million settlement involving the small firm that developed Redux, Interneuron Pharmaceuticals Inc. of Lexington, Mass.

'Adverse Events'

Federal rules require pharmaceutical companies to collect and quickly send to the FDA any reports of "adverse events" involving users. But in both the Texas trial -- in federal court -- and an ongoing one in state superior court in New Brunswick, N.J., the effectiveness and staffing of American Home's safety department were central issues.

There was testimony that at critical junctures, American Home was receiving reports of heart-valve problems but not passing them on immediately to the FDA. Other testimony portrayed the company as resistant to stiffening package-insert warnings about side effects.

Plaintiffs' assertion that American Home gave short shrift to safety "is just so wrong," says Robert Essner, executive vice president of the company. "American Home puts the highest possible standards on integrity, safety and regulatory compliance. We don't cut corners."

The company says the evidence didn't support the outcome of the Texas case. "There are those that have taken sections of selected company memoranda out of context to argue that AHP disregarded safety in the pursuit of profits. That argument is absolutely baseless," American Home says.

Hair Loss

Much of the evidence in the Texas case came from company insiders. At one point, a plaintiff's attorney asked company executive Axel Olsen why Pondimin's label warned of possible hair loss but not of heart-valve problems. Weren't heart-valve problems worse than hair loss?

"One would really need to have more information than simply the term in order to say one was more serious than the other," Dr. Olsen said, in a reply that angered Mr. Jones, the juror. "How could he not know that? A human life is worth more than hair damage," the juror says.

Another setback came when Bernard Poussot, president of global pharmaceuticals at American Home's Wyeth-Ayerst unit, testified that "similar issues" to the heart-valve problems had been seen "as early as 1960." He couldn't be reached for comment, but American Home says he was referring to reports about Aminorex, a diet drug sold in Europe. Although testimony presented no specific link between the 1960 date and Pondimin or Redux, Mr. Jones says the long history of red flags helped persuade him as a juror to support the plaintiff's side.

In the New Jersey suit -- a class action seeking medical monitoring for those who took the drugs -- current and former American Home employees testified that the company was hard-pressed to keep up with its growing responsibility of monitoring side-effect reports. First, the company's workload increased in 1994 with American Home's acquisition of American Cyanamid Co. and its Lederle drug unit. Then, sales of Pondimin took off. Pondimin had been a minor drug since the 1970s, becoming a product of American Home via its 1989 acquisition of A.H. Robins. The drug became a big seller after a report on how to use Pondimin -- technically, fenfluramine -- with a drug called phentermine to create fen-phen, the appetite-dulling combo that ignited a craze.

An official testified to a 30% rise during the first half of 1996 in reports of "adverse events" problems with American Home's drugs, the more serious of which went into red folders. "Will this flood of red folders never end," employee Mary Frances Moeller wrote to a colleague in an October 1996 memo involving Pondimin reports. "We are in desperate need of a lull." American Home says Ms. Moeller nonetheless completed her work on time.

The company relied heavily on temporary employees to monitor and process side-effect reports. Marc Deitch, former global medical director for Wyeth-Ayerst, testified that as of July 1996, soon after Redux won FDA approval, 33% of safety staffers were temps. One monitor, Amy Myers, testified that she repeatedly complained to her boss about the burgeoning workload, including time spent training short-term temps.

The FDA, during a 1997 FDA inspection, found deficiencies in American Home's safety-monitoring computer system. According to an internal company summary of the inspection, Dr. Deitch told the FDA the problem was due to rapid growth. "He said that he wasn't making excuses, but offering this as an explanation; Ayerst, Robins, Lederle, Cyanamid, and the system simply could not accommodate the growth," the summary read.

Dr. Deitch, who has left the company, declines to comment. American Home says it has always allocated adequate resources to safety surveillance. A spokesman, noting there may have been "a little turmoil" following its acquisitions, says the company has upgraded its computers and substantially increased its safety staff.

Value Problems in Europe

A major trial issue was why American Home didn't warn the public after receiving reports of several dozen cases of heart-valve problems involving Pondimin in Europe, well before valve problems arose in the U.S. in the spring of 1997.

Fredrick S. Wilson, one of American Home's medical monitors for Pondimin, testified via deposition in the Texas trial that he took a month-long vacation in February 1995, the same time that several reports of heart-valve problems from Belgium reached the company. Dr. Wilson's deposition said that when he returned to work part-time in March, he didn't review the valve reports that had arrived during his vacation.

American Home says another staffer reviewed the reports in his absence. Its defense was that the European reports it got weren't alarming because the heartvalve leaks were very mild, of a kind that isn't uncommon in the population at large. And it said the Belgian cases -- the bulk of the reports -- were complicated by the fact that many patients also took a concoction of Chinese herbs to lose weight.

One juror, Peggy L. Jacobs of Edgewood, Texas, says she was willing to give American Home the benefit of the doubt on the Chinese herbs. But she says she couldn't forgive the company's repeated efforts to avoid putting prominent warnings on the the drug's package insert.

Pulmonary Hypertension

The first trial evidence about the warnings dated back to June 1994, when Dr. Wilson found out that the company had reports of 41 Pondimin users coming down with primary pulmonary hypertension, while the package insert was showing just four, according to his testimony. Dr. Wilson testified that he proposed updating the warning to reflect additional cases of the dangerous disorder and that company officials initially agreed to a draft change. But the warning wasn't strengthened until two years later, according to Ms. Myers's testimony in the New Jersey case.

That was in July 1996, about two months after Pondimin's chemical cousin, Redux, won FDA approval in a close vote, in the wake of considerable debate over side effects. Lawyers for American Home Products say the company didn't update the package insert sooner because it was waiting for results of a large-scale study on the incidence of the lung disorder. The company adds that the FDA told it in 1994 that the warning didn't need to be updated.

But Mr. Jones, the Texas juror, says the delay seemed like an attempt to sweep the issue under the rug until Redux won approval. And in the New Jersey case, Dr. Deitch, who was responsible for the label at the time, testified that it was a "mistake" not to update the Pondimin label's reference to just four pulmonary-hypertension cases. "I'm not saying we shouldn't have changed the number four. We should have," he testified.

'Black Box'

During the approval process for Redux, the company argued against a "black box" warning for pulmonary hypertension on the package insert, which is sent to pharmacies and printed in doctors' reference manuals. In these warnings, the cautionary information is set off in a bordered box to draw attention. Lawyers for Ms. Lovett produced a document circulating at American Home showing a consultant had said Redux sales could be as much as 50% lower if there was a black-box warning.

The memo was solely for "informational purposes" for the marketing department and didn't have "any impact" on the company's labeling negotiations with FDA on Redux, a spokesman says.

On Feb. 27, 1996, Wyeth-Ayerst official JoAlene Dolan wrote to the group assigned to help her prepare a presentation opposing the black box. "The meeting with FDA yesterday was a tremendous success!" she wrote to this SWAT group (Special WyethAyerst Team). "No black box!" Ms. Dolan, has left the company and couldn't be reached for comment.

Marc Farley, a lawyer for American Home in the New Jersey case, says the Dolan memo "is a classic example of an out-of-context memo" used by plaintiffs' lawyers to assert misleadingly that the company wasn't concerned about safety. Since the company's top medical experts thought a black box wasn't necessary, it was natural for Ms. Dolan to be pleased when the FDA agreed, he says. Redux won FDA approval in April 1996 without the black box.

(It is unclear what elements of the approval have piqued the FBI's curiosity. Its agents are still trying to determine whether there is evidence warranting a criminal investigation, according to people familiar with the matter. Plaintiffs' attorneys are eagerly aiding the probe.)

Damage Control

Four months later came some bad news: A study published in the New England Journal of Medicine provided further evidence linking primary pulmonary hypertension to diet-drug use.

One of American Home's immediate reactions was to strategize on how to prevent the paper from scaring off customers. Kelly Davis, a doctor in charge of monitoring the drugs' safety for American Home, wrote to Ginger Constantine, a high-ranking doctor at the company: "In order to be truly convincing that the risk of primary pulmonary hypertension is worth taking, I would recommend making a comparison of risks for another drug or medical risk that physicians are more comfortable with, such as the risk of dying from an anaphylactic reaction associated with the use of an antibiotic." American Home declines to comment on this memo or on whether it took any safety steps in reaction to the New England Journal of Medicine paper.

Other testimony told of employees being instructed to delay processing new heart-valve reports. Ms. Myers, the safety monitor, testified in Texas that the company received reports of heart-valve problems from a doctor in Fargo, N.D., on March 6, 1997; she said that soon afterward she entered about 14 cases into the firm's computer system and gave them identifying "manufacturer control numbers."

But when Ms. Myers updated her superiors on the cases five days later at a safety-surveillance meeting, Dr. Constantine told her she shouldn't have entered the cases into the computer because the information the Fargo doctor gave on the phone wasn't detailed enough. "I basically told her that I thought she had jumped the gun," Dr. Constantine testified.

Files Overwritten

Dr. Olsen, vice president of global medical operations at the Wyeth-Ayerst unit, suggested at the same meeting that "the cases could be canceled," Ms. Myers testifed. In his own deposition, Dr. Olsen denied telling her to "erase" the entries and replace them with other reports; reached by phone, he declined to comment. Dr. Constantine couldn't be reached.

Following the meeting, Ms. Myers testified, she overwrote the files and reused numbers she had given to diet-drug reports. According to records at the FDA, American Home didn't inform the agency of the North Dakota incidents until April 11, after sending officials to Fargo and the Mayo Clinic in Minnesota, which was working with the Fargo doctor.

The FDA, in a Dec. 4, 1997, inspection report, told American Home that it had improperly reused the manufacturer's control numbers. The FDA also alleged that American Home was 11 business days late in reporting the Fargo problems. Drug firms are required to inform the agency of any serious safety problems "as soon as possible," but no later than 15 days after hearing of them.

"It did seem like they were trying to buy some time, stretch it out as long they could and keep selling" the diet drugs, says Ms. Jacobs, the Texas juror.

The company says it believes it "reported everything according to FDA guidelines." Mr. Farley, its lawyer, says the original reports opened by Ms. Myers "were not complete, and they would not have provided the FDA with meaningful information." He acknowledges that it was a mistake for her to overwrite the manufacturer's control numbers.

Lars Noah, a food-and-drug-law expert at the University of Florida in Gainesville, says that even a company that has an incomplete report from the field should be able to get enough to file a report to the FDA within in a day or two. "The obligation to file the 15-day report kicks in immediately," he said. "If there's going to be follow-up ... that's a subsequent report to FDA. You don't decide internally, 'Let's get all our facts straight and only when we're sure there's a problem here do we raise the red flag with the FDA.' "

American Home has said that it has resolved the FDA concerns in the inspection report, in part by a computer-system overhaul that makes it impossible to overwrite a report once it is entered.

Quadruple-Urgent

By July 1997, evidence of heart-valve problems was growing. A Mayo Clinic study on the subject, set for publication late in August, was instead released by Mayo at a July 8 news briefing.

American Home heard about the plan for an accelerated release. In an internal memo dated July 1 and headed "URGENT URGENT URGENT URGENT," marketing employee Gerald V. Burr warned officials that the Mayo report might leak before the news conference and provided a "standby statement" for responding to inquiries.

"Well, does it say anywhere under the four urgents here that there's one iota of concern for the people who have the heart-valve problems?" Kip Petroff, an attorney for Ms. Lovett in Texas, asked Carrie Smith-Cox, formerly vice president for women's health at Wyeth-Ayerst, during a video deposition played during the trial.

"This memo does not refer to that," Ms. Smith-Cox replied. "However, that would also not have been within the responsibilities of the people charged with writing the standby statement to look at the overall plan." American Home says Mr. Burr's memo was "simply a heads-up" to prepare for questions from the media.

Meanwhile, although Redux had been approved without a black-box warning, documents and testimony from a former FDA official show that the idea of a black-box warning for the newly discovered heart-valve problem was under discussion at the agency in July 1997. American Home initially argued against it, and in succeeding weeks, relations with the agency grew tense. In a Sept. 5 internal FDA memo introduced at the Texas trial, FDA scientist David J. Graham wrote that he and colleague Lanh Green had "have become concerned about the diligence of Wyeth-Ayerst in pursuing leads and obtaining and reporting full clinical details of cases to FDA."

American Home says it never heard such criticism from the FDA. It also says the scientific evidence at the time didn't warrant a black-box warning because the heart-valve incidents were "anecdotal case reports" that needed evaluation.

About a week later, according to testimony, the FDA asked American Home officials to come to agency headquarters. At the meeting, the FDA says, it asked the officials to recall the drugs. American Home says that it would have withdrawn the drugs from the market even if the FDA hadn't asked it to. ]]> American Home Products To Appeal Court's Ruling In Deborah Lovett vs. American Home Products http://www.yourlawyer.com/articles/read/1193 Fri, 06 Aug 1999 00:00:00 -0700 http://www.yourlawyer.com/articles/read/1193
"We are disappointed by today's ruling," says Bob Schick of Vinson & Elkins, a Houston-based attorney for American Home. "We feel the evidence presented in this case demonstrated that the company acted responsibly and lawfully in marketing and monitoring the safety of the diet drug Pondimin."

"There simply is no scientific study that has established a causal link between the use of Pondimin and the heart problems claimed by Mrs. Lovett," Mr. Schick adds.

Deborah Lovett's longstanding history of heart problems began in 1980 when she was 17 years old. In 1990, prior to her use of the diet drugs, she was diagnosed with mitral valve prolapse syndrome with recurrent symptomatic palpitations, a condition caused by myxomatous degeneration of the mitral valve. In fact, her treating cardiologist, the only physician who actually examined Ms. Lovett as a patient, testified that her heart valve problems were caused by myxomatous degeneration and not by use of phen-fen. She had this condition prior to treatment with phen-fen, has evidence of it today and will not require surgery in the future.

Pondimin and another diet drug, Redux, were voluntarily withdrawn from the market in September 1997 by Wyeth-Ayerst Laboratories. Wyeth-Ayerst did not make or market the drug phentermine, which also was taken by the plaintiff in tandem with Pondimin as the so-called "phen-fen" combination.

Wyeth-Ayerst Laboratories, the pharmaceutical division of American Home Products Corporation (NYSE: AHP), is a major research-oriented pharmaceutical company with leading products in the areas of women's health care, cardiovascular, and metabolic disease therapies, central nervous system drugs, anti-inflammatory agents, vaccines, and generic pharmaceuticals.

American Home Products Corporation is one of the world's largest research-based pharmaceutical and health care products companies. It is a leader in the discovery, development, manufacturing and marketing of prescription drugs and over-the-counter medications. It is also a global leader in vaccines, biotechnology, agricultural products and animal health care. ]]> Jury Selection In Diet Drug Case http://www.yourlawyer.com/articles/read/1192 Wed, 31 Mar 1999 00:00:00 -0800 http://www.yourlawyer.com/articles/read/1192
Opening statements were expected to begin later today in the lawsuit filed in state district court by Sandra Moore against American Home Products Corp., parent of pharmaceutical company Wyeth-Ayerst Laboratories.

Jury selection continued this morning with about 50 people remaining in the pool. Prospective jurors were being questioned extensively about their knowledge of the drugs, said Ms. Moore's attorney, Michael McGartland.

"Only two people on the panel didn't know about fen-phen," he said.

Ms. Moore, who now lives in Missoula, Mont., claims she wasn't warned about the risks of taking fenfluramine, marketed by Wyeth-Ayerst as Pondimin, and dexfenfluramine, a similar drug later sold by the company as Redux.

The two drugs, which have been yanked from the market, make up half of the so-called "fen-phen" combination prescribed to thousands of patients to promote weight loss. The other half, phentermine, has not been linked to heart problems when taken alone and is still on the market.

Doctors found mild heart valve damage after Ms. Moore, 52, took fen-phen for 10 months in 1996. Now on medication for her condition, she seeks damages exceeding $10 million.

"She has congestive heart failure and heart valve disease as a result of taking the pills," McGartland said.

The lawsuit is believed to be the first to reach a courtroom over the issue of heart valve damage, and experts said a victory for her could prove key to other cases.

"Its going to encourage a lot of lawyers and clients that are right now sitting back and watching," said Dallas attorney Kip Petroff. "I know for a fact that (American Home Products) is banking on winning so it'll have the exact opposite effect."

The company has reportedly spent millions settling five cases involving primary pulmonary hypertension. Defense lawyer Bill Sims said he looks forward to putting the facts before the Texas jury.

"There's a lot of misinformation circulating about these drugs and why they were voluntarily withdrawn from the market," he said. "We are going to tell it like it is."

Fenfluramine carried labels starting in 1988 warning that in rare instances it causes primary pulmonary hypertension, a potentially fatal disorder.

Wyeth-Ayerst has been hit with hundreds of lawsuits since it pulled fenfluramine and Redux off the market in 1997 at the Food and Drug Administration's request.

A Mayo Clinic study linked the drugs to potentially fatal heart valve damage. ]]> Heart Valve Abnormalities Examined In Relation To Duration Of Diet Drug Use http://www.yourlawyer.com/articles/read/1191 Tue, 09 Mar 1999 00:00:00 -0800 http://www.yourlawyer.com/articles/read/1191
Duke researchers said in a report prepared for the annual meeting of the American College of Cardiology that they found evidence on a cardiac diagnostic test of "mild or greater aortic regurgitation" in 8.8 percent of 1,163 patients who used fen/phen for three months or more. In comparison, they detected the same problem in 3.6 percent of a control group of 672 overweight people who had not taken the drug.

In a study funded by Wyeth-Ayerst Laboratories, makers of the "fen" in fen/phen, the research team determined that the prevalence of this valve problem was related to the duration of time the drug was used. Among those who used the diet drug combo for less than six months, there was no increase in mild or greater aortic regurgitation, but "the longer people in this study took the drugs, the greater the likelihood that they showed some abnormality on an echocardiogram," said Duke cardiologist Dr. Thomas Ryan.

He added that most of the cases of aortic regurgitation noted by the research team were graded as "trace or mild. In our clinical experience, most patients with mild aortic regurgitation have few if any symptoms because the heart can compensate for this leakage," Ryan said.

Aortic regurgitation occurs when blood leaks from the aorta -- the large artery that distributes blood to the body -- back through the aortic valve into the left ventricle, the heart's main pumping chamber. Ryan said that while the likelihood of developing the leaking valve increased the longer a person took fen/phen, it didn't mean the problem became more and more severe over time.

Ryan also said that the Duke cardiology team noted a statistically significant increase in shortness of breath during exercise in study patients who used fen/phen (26 percent) compared to patients who didn't (21 percent). Shortness of breath is not associated with the regurgitation, however, so the relationship between that finding and use of the drug isn't clear, he said.

The "fen" in fen/phen refers to fenfluramine. It and a similar drug were withdrawn in September 1997 due to reports of heart-valve problems among a small percentage of the 4 million people who took the fen/phen combination.

Ryan said in an interview that results of the new study are similar to several smaller studies on fen/phen use that have been reported in the last year. The difference in this study is that more patients were included, and the study was designed to examine duration of drug use. To help them make their analyses, the researchers used an echocardiogram taken on all the patients. An echocardiogram is a diagnostic test that uses ultrasound to picture both a heart's structure and how blood flows into, within, and out of the heart.

Medical information on the 1,163 patients who used fen/phen for more than three months was gathered from 33 different diet clinics around of the country. Among other conclusions, the researchers found:

no significant difference in the incidence of aortic valve regurgitation in people who used the drug for three to six months, compared to the control group.

no significant difference in the prevalence of regurgitation in the mitral valve between the two groups. Mitral valve regurgitation was noted in 2.5 percent of the diet drug patients compared to 1.5 percent in the control group. The mitral valve controls the flow of blood between the left atrium, where blood is received from the lungs, and the left ventricle, the pumping chamber.

While Ryan considers the study the most definitive to date, he noted that it had to rely on retrospectively collected information - it was not a randomized, prospective clinical trial - and that there were gender and racial differences between the group that used drugs and the group that didn't. For example, there were more white women in the treated group compared to the control group. "It's the best study that can be done given the nature of the issue," he said.

Working with him on the study were, from Duke, cardiologists Dr. James Jollis, Dr. Carolyn Donovan and Dr. Joseph Kisslo, and from Wyeth-Ayerst, Dr. Ginger Constantine and Dr. Kelly Davis. ]]> Weight-Loss Wars http://www.yourlawyer.com/articles/read/26 Mon, 15 Feb 1999 00:00:00 -0800 http://www.yourlawyer.com/articles/read/26
She never bought the gown. She began suffering dizzy spells and shortness of breath and quickly stopped taking the drugs. But soon the 29-year-old tennis player and former captain of her high school swim team could hardly walk up the stairs.

Medical tests showed Linnen had developed primary pulmonary hypertension from one of the diet drugs, her surgeon said. He inserted a tube in Linnen's chest and plugged it into a computerized box that would pump medicine to her heart. On Feb. 22, 1997, Linnen was released from a Boston hospital. Her fianc drove her home and carried her up to her apartment. But when he put her on the bed, she cried, "Something's wrong." Linnen couldn't breathe. Her fianc's call to 911 came too late.

"Surprise." Nearly seven months after Linnen died, Pondimin, one half of the popular fen-phen combo, and Redux, a stronger version of Pondimin, were withdrawn from the market. The reason: The Food and Drug Administration had determined that the drugs could cause heart-valve problems, which medical experts say are related to pulmonary hypertension. Medical experts have since attributed more than 200 cases of pulmonary hypertension in the United States to Pondimin and Redux. Of those, at least 40 have already resulted in death, records and interviews show.

Today, with the first of over 1,000 lawsuits involving the two drugs set for trial, questions loom. When they pulled the drugs from the market, the companies that sold them, Philadelphia-based Wyeth-Ayerst (Pondimin and Redux) and Boston-based Interneuron (Redux), issued statements indicating that the heart-valve problems had come as a "surprise."

Company documents filed in connection with pending litigation tell a different story. During 1995 and 1996, while the label on Pondimin noted only four cases of pulmonary hypertension associated with the drug, Wyeth received reports, mostly from Europe, of as many as 62 cases of the disease. Technically, the companies didn't have to tell the U.S. Food and Drug Administration about such "adverse events" from abroad because pulmonary hypertension was already mentioned as a possible side effect on the drug's label. But the companies knew about more cases linked to the drugs. In their application to have Redux approved by the FDA, for instance, the companies noted 132 pulmonary hypertension cases linked to the drug. A Wyeth memo stated: "Now that a flow (stream? river?) of international serious reports has begun . . . we've been talking about reportability of them." Another memo listed 101 cases of pulmonary hypertension linked to Pondimin or Redux-on top of the previously reported 132 cases. Wyeth says it reported all domestic adverse events to the FDA and that the agency knew the drugs could cause pulmonary hypertension.

Despite the apparent problems, Wyeth and Interneuron pressed ahead. During negotiations with the FDA over the labeling of Redux, FDA officials proposed affixing a "black box" label, cautioning that some users could develop pulmonary hypertension. But according to a Wyeth official's deposition, the company wanted to "avoid a public panic by implementing a black-box warning" that could hurt sales. The companies prevailed. A congratulatory Wyeth E-mail sent to the "SWAT Team" that conducted the negotiations with the regulators said: "The meeting with the FDA yesterday was a tremendous success! No black box!"

Scribbles. But even some Wyeth officials were divided over the safety issue. Joseph Sonk, director of the women's health division, noted in an August 1996 memo that an in-house lawyer had wanted a much stronger warning on the Redux label. "SC strongly favors black box," Sonk wrote, referring to attorney Sheila Connor. The note only surfaced last summer. Wyeth would not allow Connor to answer questions about the note in a deposition.

There was other evidence of concern by the companies. A "Standby Statement and Q and A for Wyeth-Ayerst Laboratories" was prepared as an informational aid for physicians prescribing Pondimin. In the margin of the document, a Wyeth attorney scribbled some notes. In the sentence, "Pondimin has been used safely and effectively . . . ," the attorney edited out the word safely. On another page, next to the word safe, the lawyer wrote, "Can't say this" and "Don't use the word safe or safely in an unqualified fashion."

Mindful of the concerns about the drugs, Wyeth and Interneuron pressed the FDA. Interneuron turned to California Rep. Tom Lantos to try to close an FDA meeting about the drugs' safety, prohibiting doctors and scientists from several health-advocacy groups from attending. A Lantos aide said his boss did not recall the meeting at the congressman's office in February 1997. A review of political contributions shows that officials of Interneuron, including its board chairman, CEO, and some of their wives, contributed to Lantos and his son-in-law, former Rep. Dick Swett, for whom Lantos was raising funds in 1996 and 1997.

The FDA yielded. It declined to press for the black-box warning and, in a highly unusual process, overrode the objections of FDA safety officers approving the use of Redux in 1996. But at the FDA, doctors were concerned about pulmonary hypertension. Some Interneuron executives were also troubled by the potential link. According to a March 1994 FDA memo, Interneuron Executive Vice President Bobby Sandage said in phone calls to the agency that the company had such concern about pulmonary hypertension that "it might be strong enough to consider withdrawing the NDA," or new-drug application. But Interneuron didn't pull the application. In a later call, the memo says, Sandage told an FDA safety officer that the company had decided that "withdrawal, from a financial standpoint, was really out of the question because the company would be ruined." A few months later, another FDA memo recorded that Sandage said Interneuron had "nothing to lose and would stop at nothing to get dexfenfluramine [Redux] approved."

In fact, Interneuron's plan to market Redux in the United States was a major element in a stock prospectus it was circulating on Wall Street in 1997. Wyeth, too, had a stake in winning FDA approval for Redux. Market analysts expected the companies to generate combined revenues of more than $500 million a year from the sales of Pondimin and Redux in the United States.

Until now, the full fen-phen story has not been told. Wyeth has been quietly settling cases with plaintiffs related to pulmonary hypertension and heart- valve disease, often demanding confidentiality agreements. (Interneuron is currently trying to finalize a general settlement by itself.) But last year, two Dallas lawyers persuaded Wyeth's and Interneuron's attorneys to go forward with depositions and discovery. Kip Petroff and Robert Kisselburgh represent about 100 plaintiffs who have either pulmonary hypertension or heart-valve damage. The litigation has generated millions of documents. Among them: notes from Wyeth lawyers about how "safe" Pondimin was. Petroff was dumbfounded. "I was shocked. I mean, lawyers are always cautious, but if you can't call your own drug safe, why are you pushing it?"

Central to the litigation pending against Wyeth and Interneuron are two questions: What did the companies know, and when did they know it? Regarding pulmonary hypertension, Wyeth's former medical monitor, physician Frederick Wilson, testified in a deposition that he found company reports back in 1994 showing 37 confirmed Pondimin-related cases. Wilson wanted a new label to reflect the increase in reports of pulmonary hypertension, and he wrote a memo urging Wyeth executives to change the Pondimin label, which mentioned only four such cases. "Everyone agreed in June 1994 that the label needed to be changed," Wilson said. But Wyeth didn't change the label until June 1996-after Redux had been approved for sale by the FDA. Petroff asked the reason for the delay. Wilson professed not to know. "It seems like quite a long time," he said. A Post-it note found on the label change form dated May 1995 suggested one possible answer. The note, from Wyeth's top medical affairs director, Marc Deitch, said, "[we] need to discuss implication re: dexfenfluramine before proceeding." In a deposition taken two months ago, Deitch said the delay was due to the company's desire to have the Redux and Pondimin labels match. But according to the Physicians' Desk Reference of 1997, the two drugs' labeling is different. Had Wyeth changed the label in 1995, it would have raised a red flag for the FDA panel studying the Redux application, experts say, but that didn't happen. "Wyeth did not want to alert the FDA that it was seeing so many new cases of pulmonary hypertension while the application for Redux was still waiting for approval," attorney Petroff says. "It would have hurt the Redux application."

Wyeth and Interneuron also had information about heart-valve problems among some users of the diet drugs, documents show. In the Redux approval application sent to the FDA, the companies reported several dozen cases mentioning heart-valve irregularities, according to FDA officials. Wyeth says the heart-valve references were not seen as a "signal" of a link between Redux and heart-valve disease. But "red flags should have gone up," says attorney Kisselburgh. Today, Wyeth officials are proffering new studies that they say show that alarms about the drugs were overstated. A company-funded study at Georgetown University said there was almost no link between their drug and heart damage. But that study was rejected by the New England Journal of Medicine last spring when it was submitted for publication. The editors insisted that the study be redone. "After they redid it," says the journal's deputy editor, Gregory Curfman, "there was a significant link between the drug and heart-valve irregularity." A senior official at the FDA says, "Most of these new studies from Wyeth only deal with short term exposure. . . . clearly, had the drugs stayed on the market longer, we would be seeing many more and more-serious cases of heart-valve damage and pulmonary hypertension."

BEYOND FEN-PHEN

The scramble to develop a miracle diet drug

Developing a safe, effective diet pill remains the Holy Grail for drug companies. "It's a mad scramble," says Arthur Frank, medical director of the George Washington University Obesity Management Program. "Every significant pharmaceutical company in the world is working on an obesity drug." And no wonder: By most estimates, over half of all American adults-some 97 million people-are overweight. "There aren't a lot of drugs where you can say that half the population could potentially be interested," says Louis Tartaglia, a senior researcher at Millennium Pharmaceuticals Inc. For now, however, the diet drug pickings are slim. Meridia was the only obesity medication to hit the market last year. Knoll, Meridia's manufacturer, says the drug is for folks who are about 30 percent beyond their ideal body weight. Still, the weight-loss effects are modest, and doctors say the drug can elevate blood pressure.

Orlistat, also known as Xenical, is expected to be approved by the Food and Drug Administration by June. Produced by Swiss drug maker Hoffmann-La Roche, Orlistat blocks up to 30 percent of the fat absorbed into the intestines. People who take the drug and binge on fatty foods can experience unpleasant side effects, like "Explosive diarrhea when you least expect it," says Frances Berg, editor of the Healthy Weight Journal.

No miracle. But Orlistat is no wonder drug. "Weight loss averages 7 pounds a year more than the placebo group-and that's for people who weighed 220 pounds," says Jules Hirsch, a Rockefeller University professor and member of the FDA advisory committee.

After Orlistat, the next obesity drug is at least three years away. Drug maker Amgen is experimenting with leptin, a hormone that tells the brain to stop eating. It only comes in an injectable form, and weight loss is modest to date, so sales are expected to be limited. Pfizer is in the early stages of testing drugs to block neuropeptide Y, a powerful eating signal. And several companies are trying to unlock the secrets of Beta 3, a receptor that appears to rev up the metabolism. "We are where we were with diabetes in the 1920s," says Frank. "We knew that blood sugar had to be regulated, but we didn't know how."]]> Diet Drugs: Let Buyer Beware http://www.yourlawyer.com/articles/read/1190 Tue, 05 Jan 1999 00:00:00 -0800 http://www.yourlawyer.com/articles/read/1190
Now lawsuits against the drugs' manufacturers are pending nationwide, claiming fen-phen damaged people's heart valves. The Food and Drug Administration banished the drugs from the market in September 1997, after years of inaction despite numerous reports of harmful side effects.

Up against the billion-dollar weight-loss industry, the FDA may not be able to protect consumers against dangerous diet drugs, said Julia Wyman, a New Haven lawyer with clients who may join the parade of litigants against fen-phen manufacturers.

"Our position is that manufacturers knew or should have known that the drugs were being used in combination and failed to warn physicians and the public about the dangers," Wyman said.

She said the FDA is handicapped because it often must rely on studies financed by the pharmaceutical companies.

Phentermine was approved for sale in 1959 and fenfluramine in 1973. In the past, they were often used separately to curb appetite. However, a study published in 1984 showed they could achieve the same weight-loss results, with fewer side effects, if they were used together at lower doses.

In July 1997, the Mayo Clinic reported that 24 patients who had taken fen-phen had developed symptoms of heart-valve damage. Five required open-heart surgery to repair damage to one or more of their four heart valves. Researchers are still not certain but theorize that heart valve injury is caused by the alteration of serotonin metabolism in the body.

Early reports that as many as 30 percent of fen-phen users may have been harmed turned out to be overstated, said J.P. Smith, a spokesman for the American Society of Bariatric Physicians, doctors who specialize in treating obesity.

Smith said a survey of 1,400 members found no cases of primary pulmonary hypertension, the most serious complication. Still, "I would also say that people who have taken these medications should be aware of the symptoms and get an echocardiogram," he said.

Other problems that have been identified include aortic insufficiency, a condition of the heart that can be seen through an echocardiogram, and mitral valve regurgitation, which is a leaking heart valve.

In some cases, the problem can be corrected with medication; in others, surgery may be required.

"Some people affected took the drug for only six months and now need a heart and lung transplant in order to survive," said Wyman.

She questions the society's claim that only a fraction of the people who took the drugs have been adversely affected.

"Some people may not even be aware that they have a problem, or they may be having symptoms that they attributed to other things," she said.

The public's desire for a quick weight-loss fix and the tremendous potential profits for companies have created a situation of "let the buyer beware," Wyman said.

"I think it is very prudent for the public to take heed of the fact that these drugs were FDA-approved and promoted by doctors." ]]> Outdated Label May Have Led To Toxic Combination Of 'Fen-Phen' http://www.yourlawyer.com/articles/read/1189 Mon, 28 Sep 1998 00:00:00 -0700 http://www.yourlawyer.com/articles/read/1189
Too much serotonin damages blood vessels, particularly in the lungs, and may also harm heart valves. Such damage may have led to primary pulmonary hypertension and heart valve lesions in a small number of the millions of Americans who took the anti-obesity drug combination from 1992 until 1997, when one of the drugs, fen-fluramine, was voluntarily withdrawn by its manufacturer.

The other drug, phentermine, is still used to treat obesity. Because the two drugs were never in one pill, their use in combination didn't require US Food and Drug Administration approval.

The two drugs should never have been prescribed together, say researchers Timothy J. Maher, the Sawyer Professor of Pharmaceutical Sciences and director of the Division of Pharmaceutical Sciences at MCP and a lecturer in MIT's Department of Brain and Cognitive Sciences; MIT visiting scientist Dr. Ismail H. Ulus, professor of pharmacology at the University of Uludag in Bursa, Turkey; and Dr. Richard J. Wurtman, the C.H. Green Distinguished Professor at MIT and director of the Clinical Research Center.

Because of omissions on drug labels, similarly dangerous side effects may result from pairing antidepressants such as Prozac with phentermine, as well as with over-the-counter cold remedies that contain ingredients such as pseudoephedrine (found in Sudafed), phenylpropanolamine (found in Accutrim) and ephedrine, the researchers found.

SEROTONIN MECHANISMS

The body has two mechanisms for removing serotonin: absorption into platelets, which use it for clotting, and the serotonin-destroying enzyme monoamine oxidase (MAO). Some drugs block serotonin from being taken in by platelets; others inhibit the activity of MAO. By using two of these drugs at the same time, the body's ability to keep serotonin levels in check is virtually wiped out.

Fenfluramine, like many antidepressant drugs, stops plasma serotonin from being taken up into platelets. Phentermine, the investigators found, raises serotonin by another chemical action: it inhibits the MAO that destroys serotonin. Neither drug has caused these problems when taken alone.

That the two drugs taken in tandem would lead to a dangerous excess of serotonin would have been obvious to any physician or pharmacist who knew that phentermine is an MAO inhibitor. But apparently few paid much attention to this, even though scientific papers published in the 1970s first demonstrated it, because the drug's label doesn't say it.

"These new findings show that it's critically important that drug labels be complete and up to date, and that there can be great harm when they're not. The fact that phentermine is an MAO inhibitor should have been stated on its label," Professor Wurtman said.

Professor Maher said that the information that appears on drug labels, in the Physician's Desk Reference and on package inserts that reach consumers is negotiated between the manufacturer and the FDA.

"When the labels for phentermine and Sudafed were negotiated, their MAO inhibitory activity was not known or appreciated or considered to be important. And apparently there was no requirement for phentermine's label to be updated 20 years ago when it was first shown to be an MAO inhibitor," he said.

"The new findings also probably explain why only a handful of the tens of millions of patients outside America who took drugs in the fenfluramine family without phentermine developed pulmonary hypertension or heart valve lesions, and almost all of these people were also taking other drugs that we have found are unrecognized MAO inhibitors," Professor Wurtman said.

He is the co-inventor of the use of Redux, an MIT-patented drug, to treat obesity. Redux, or dexfenfluramine, is the half of the chemical compound of fenfluramine that directly works on serotonin metabolism. Redux also was withdrawn from the market in 1997, although there was little evidence that Redux given alone caused heart or lung damage.

The researchers also found that common over-the-counter remedies for colds and obesity that contain ingredients such as pseudoephedrine (found in Sudafed), phenyl-propanolamine (found in Accutrim) and ephedrine also act as MAO inhibitors, although they are not labeled as such. This could be damaging to patients who also take antidepressants such as Prozac, Effexor, Zoloft or Paxil, which, like the fenfluramines, inhibit serotonin uptake, and whose labels state that they should never be taken with MAO inhibitors.

Because the label on phentermine didn't say anything about its ability to inhibit MAO, "people didn't recognize that phentermine had significant MAO inhibiting activity," Professor Maher said. "Because this information is still omitted from the drug's label, many patients are now taking it with another serotonin-uptake blocker, Prozac, to lose weight."

Herbs, which are unregulated, are another complicating factor, Maher said. St. John's Wort and ma huang--both taken for mood elevation and weight loss--may also be MAO inhibitors, he said.

Although nobody has been identified as having developed lung or heart diseases after taking Prozac and Sudafed, for instance, Professor Maher said this possibility needs to be investigated carefully.

"Until now, there was no particular reason to think that these classes of drugs would interact in the blood, and physicians examining patients with pulmonary hypertension or heart valve disease might not have asked specifically about how often the patients took the drugs," he said.

FEN-PHEN HISTORY

Although the amphetamine-like phentermine was first used as an appetite suppressant in the 1960s and became available in a generic version around 1980, it got new life in the United States after 1992 when it was paired with another anti-obesity drug, fenfluramine. The drugs were combined to cancel out the tendency of one to act as a stimulant and the other as a depressant. They were joined "for what they did to the brain, and not analyzed for their consequences for the blood," Professor Wurtman said.

Serotonin in brain cells is involved in transmitting nerve impulses, and the antidepressant and anti-obesity drugs that block serotonin uptake into platelets are designed to enhance this effect. The serotonin in blood plasma, made by special cells in the intestines, is the only source of serotonin for the platelets, which release the chemical when they form clots to stop bleeding but are unable to make it themselves.

A rare intestinal tumor called carcinoid releases enormous amounts of serotonin into the plasma, swamping the body's two mechanisms for removing serotonin. Carcinoid causes the same pulmonary hypertension and heart valve lesions found in a small number of people taking fen-phen.

About two years ago, Professor Maher started to look more closely at the problems seemingly tied to fen-phen. In a search of literature that is readily available to physicians, pharmacists and students, he quickly discovered that articles published in the 1970s identify phentermine as an MAO inhibitor.

While the labels on fenfluramines and other serotonin uptake-blockers clearly warn against combining these drugs with MAO inhibitors, no red flags about phentermine's MAO-inhibiting ability were raised because the bible of drug facts -- the Physician's Desk Reference -- and the drug's own FDA-approved label don't list it as an MAO inhibitor.

"To this day, if you ask 1,000 physicians or pharmacists if phen-termine is an MAO inhibitor, they will say no. This information was buried. It never surfaced after the 1970s and we're reconfirming it now," Professor Maher said.

The authors' rediscovery of phentermine's MAO-inhibiting effect was partly accidental. Professor Wurtman wanted to see whether phentermine affected another blood chemical, dopamine. After he gave a low dose of phentermine to volunteers, he found that their dopamine levels increased. As a control, he also measured serotonin in platelets, and was surprised to find that platelet serotonin increased much more, an effect that could only have resulted from MAO inhibition. Dr. Ulus then confirmed this action in lungs and other tissues in rats.

Professor Maher has no commercial associations related to fenflur-amines or phentermine. Dr. Ulus has no commercial associations. Redux was licensed to several companies, including Interneuron Pharmaceuticals Inc. of Lexington, of which Professor Wurtman is a director.

These studies were supported in part by grants from the National Institutes of Health and the Center for Brain Sciences and Metabolism Charitable Trust. ]]> Doctors say Fen-Phen causes heart disease http://www.yourlawyer.com/articles/read/45 Tue, 08 Jul 1997 00:00:00 -0700 http://www.yourlawyer.com/articles/read/45
"Our conclusion is simple," Dr. Heidi Connolly of the Mayo Clinic said at a news conference Tuesday. "We are concerned that the Fen-Phen combination may have important implications regarding heart valve disease."

The preliminary finding, which was unexpected, will be published in the August 28 edition of New England Journal of Medicine. In an unusual move, the editors of the journal decided to release the information early given the impact on public health.
Mayo Clinic press conference on Fen-Phen's potential side effects

At the same time, the Food and Drug Administration began sending letters to thousands of doctors asking them to immediately check fen-phen patients for valve problems and report them to the agency.

The urgency with which the journal and the government treated the information was unusual and reserved for only the most serious public health matters.

Connolly, the chief author of the report, stressed that the findings were preliminary and that "more information is needed." But she urged users of the drug to take precautions.

"It's really important that patients discuss these findings with their physicians and weigh risks and benefits," she said.

Added Dr. Donald Hensrud, a co-author of the report: "This new information adds a little bit more to the risk side of things."

Fen-Phen is a combination of two drugs -- fenfluramine, an appetite suppressant, and phentermine, a mild stimulant. When combined they create a powerful diet drug. In 1996, there were 18 million prescriptions written for Fen-Phen in the United States.

Although both fenfluramine and phentermine are FDA-approved, their combination is not. That is because ingesting the two together does not fall under FDA control.

The study documents the cases of 24 women living in the upper Midwest who had no history of heart problems. The women took Fen-Phen for six to 18 months and experienced a deterioration in the valves of their hearts.

Five of them had open-heart surgery to replace damaged or leaking valves. When the surgeons examined the defective valves they discovered the valves were covered with an unusual white coating. The valve damage caused blood to leak back into the heart, making it work harder.

"None of the patients have died. However, many have developed serious cardiovascular diseases requiring either medication or surgery," Connolly said. The valve damage also may diminish life expectancy, she said.

Although most of the women sampled were overweight, researchers discounted obesity in the results. "I've not seen any association with obesity as a primary cause of valvular heart disease. ...I don't think obesity has any factor," said Dr. Jack Crary.

Heart-valve deterioration is considered a serious condition that sometimes requires surgery. It can be a silent condition causing no symptoms for years until it becomes severe. If untreated it can lead to congestive heart failure.

Before Tuesday's announcement, primary pulmonary hypertension, a serious lung disease, was the only known serious side effect of Fen-Phen. Pulmonary hypertension is a disorder in which the arteries supplying the heart have an abnormally high blood pressure. Patients become short of breath, and heart failure can follow, then death.

Connolly said she and her associates conducted the research because they noticed a pattern of heart damage in patients taking the drug.

"We began to notice that otherwise healthy young women, presenting with this unusual form of valve disease, were also on Fen-Phen," Connolly said.

On routine doctor visits, the women were found to have cardiovascular symptoms or heart murmurs after having taken the weight-loss medications for an average of one year.

"We don't know how Fen-Phen may cause injury to the heart valves," Connolly said. "We do know that fenfluramine and phentermine alter the way the brain chemical serotonin is metabolized, and serotonin that circulates in the blood can cause [heart] valve injury."
]]> Doctors Say Fen-Phen Causes Heart Disease http://www.yourlawyer.com/articles/read/10437 Tue, 08 Jul 1997 00:00:00 -0700 http://www.yourlawyer.com/articles/read/10437
"Our conclusion is simple," Dr. Heidi Connolly of the Mayo Clinic said at a news conference Tuesday. "We are concerned that the Fen-Phen combination may have important implications regarding heart valve disease."

The preliminary finding, which was unexpected, will be published in the August 28 edition of New England Journal of Medicine. In an unusual move, the editors of the journal decided to release the information early given the impact on public health.

The preliminary finding, which was unexpected, will be published in the August 28 edition of New England Journal of Medicine. In an unusual move, the editors of the journal decided to release the information early given the impact on public health.

At the same time, the Food and Drug Administration began sending letters to thousands of doctors asking them to immediately check fen-phen patients for valve problems and report them to the agency.

The urgency with which the journal and the government treated the information was unusual and reserved for only the most serious public health matters.

Connolly, the chief author of the report, stressed that the findings were preliminary and that "more information is needed." But she urged users of the drug to take precautions.

"It's really important that patients discuss these findings with their physicians and weigh risks and benefits," she said.

Added Dr. Donald Hensrud, a co-author of the report: "This new information adds a little bit more to the risk side of things."

Fen-Phen is a combination of two drugs -- fenfluramine, an appetite suppressant, and phentermine, a mild stimulant. When combined they create a powerful diet drug. In 1996, there were 18 million prescriptions written for Fen-Phen in the United States.

Although both fenfluramine and phentermine are FDA-approved, their combination is not. That is because ingesting the two together does not fall under FDA control.

Midwest women examined

The study documents the cases of 24 women living in the upper Midwest who had no history of heart problems. The women took Fen-Phen for six to 18 months and experienced a deterioration in the valves of their hearts.

Five of them had open-heart surgery to replace damaged or leaking valves. When the surgeons examined the defective valves they discovered the valves were covered with an unusual white coating. The valve damage caused blood to leak back into the heart, making it work harder.

"None of the patients have died. However, many have developed serious cardiovascular diseases requiring either medication or surgery," Connolly said. The valve damage also may diminish life expectancy, she said.

Although most of the women sampled were overweight, researchers discounted obesity in the results. "I've not seen any association with obesity as a primary cause of valvular heart disease. ...I don't think obesity has any factor," said Dr. Jack Crary.

Heart-valve deterioration is considered a serious condition that sometimes requires surgery. It can be a silent condition causing no symptoms for years until it becomes severe. If untreated it can lead to congestive heart failure.

Not the only side effect

Before Tuesday's announcement, primary pulmonary hypertension, a serious lung disease, was the only known serious side effect of Fen-Phen. Pulmonary hypertension is a disorder in which the arteries supplying the heart have an abnormally high blood pressure. Patients become short of breath, and heart failure can follow, then death.

Connolly said she and her associates conducted the research because they noticed a pattern of heart damage in patients taking the drug.

"We began to notice that otherwise healthy young women, presenting with this unusual form of valve disease, were also on Fen-Phen," Connolly said.

On routine doctor visits, the women were found to have cardiovascular symptoms or heart murmurs after having taken the weight-loss medications for an average of one year.

"We don't know how Fen-Phen may cause injury to the heart valves," Connolly said. "We do know that fenfluramine and phentermine alter the way the brain chemical serotonin is metabolized, and serotonin that circulates in the blood can cause [heart] valve injury."]]> Fen Phen Primary Pulmonary Hypertension Side Effects Injury Attorney http://www.yourlawyer.com/topics/overview/fen_phen Tue, 08 Jul 1997 00:00:00 -0700 http://www.yourlawyer.com/topics/overview/fen_phen DOWNLOAD OUR FEN PHEN INFORMATION PACKAGE

Injured by Fen-Phen?

Fen Phen, or Pondimin (Generic: Fenfluramine) and Redux (Generic: Dexfenfluramine), has been linked to Heart Valve Disease and Primary Pulmonary Hypertension (PPH). Fen Phen was a popular appetite suppressant drug prescribed to people wishing to lose weight.

Withdrawal from the Market
In 1997, the FDA asked Wyeth-Ayerst Laboratories (American Home Products) the makers of Pondimin (Fenfluramine) and Redux (Dexfenfluramine), to withdraw its popular anti-obesity drugs from the market. American Home Products Corp. of Madison, N.J. manufactured fenfluramine under the brand name Pondimin. An American Home Products subsidiary Wyeth-Ayerst Laboratories manufactured Dexfenfluramine for Interneuron Pharmaceuticals under the name of Redux. Medical studies have linked Pondimin or Redux to heart valve disease.

Study Results
The FDA stated that in findings from doctors who evaluated patients taking Fenfluramine and Dexfenfluramine with echocardiograms, approximately 30 percent of patients had abnormal echocardiograms, even though they had no symptoms. This is a much higher than expected percentage of abnormal test results.  Additionally, a Mayo Clinic study that was published in the New England Journal of Medicine on August 28, 1997 suggested that as high as one-third of a patient sampling of Fen-Phen diet pill users had evidence of heart valve disease.  The study found that there was a high incidence of heart valve disease in patients taking these diet pills, without any other known reason for valve disease. In addition to heart valve disease, the use of Fenfluramine and Dexfenfluramine has been found to increase the risk of developing Primary Pulmonary Hypertension or (PPH). PPH is a rare disease of that causes the progressive narrowing of the blood vessels of the lungs. Studies estimate that treatment with certain appetite suppressant drugs tends to increase the chances of developing PPH by approximately 25 to 30%.

Legal Help for Fen Phen Victims
If you or a loved one took Fen Phen and suffered side effects, please fill out the form at the right for a free case evaluation by a qualified drug side effects attorney.]]>