buyhiman, Although you may not argue with the Redux and fenfluramine data, IPIC apparently is considering giving it a try. I think it is a rather futile effort on their part, but I found this yesterday. Its hard to believe that they will try to argue that 2 of 6 abnormal EKGs on Redux alone is insignificant especially when some patients with heart damage were also on Redux alone:
Questions Linger After Recall of Diet
Drugs
By RICHARD A. KNOX and RONALD ROSENBERG
c.1997 The Boston Globe
In the 1970s, when diet pills were in disrepute because of their
addictive properties, a bright, young husband-and-wife team at the
Massachusetts Institute of Technology hit upon the idea that obese
people use food as self-medication.
Neuroscientist Richard L. Wurtman and nutritionist Judith Wurtman
wondered: Couldn't a drug do the same thing to the brain's satiety
centers that high-carbohydrate snacks do - but without the calories?
The Wurtmans nurtured that idea over the years, until it bore fruit in a
revolutionary approach to weight loss: a drug called Redux that blunts
food cravings by raising levels of the brain chemical serotonin.
Their idea made diet pills respectable again. Along the way, it also
made the Wurtmans rich. Earlier this year, Richard Wurtman's stock in
Interneuron, a company he founded to exploit his research, was worth
$24.6 million. One analyst predicted $1 billion in yearly Redux sales
by 1999.
The Wurtmans' studies also put a rocket under an older
serotonin-raising drug called fenfluramine, after a 1992 study indicated
it could facilitate weight loss if taken with phentermine, a combination
that came to be called fen/phen.
But last week, the supposedly rational, science-based treatment
collapsed under suspicions that many patients on the pills may suffer
damage to heart valves.
A preliminary screening of 291 diet-pill patients from five sites
indicated that about a third had silent, or symptomless, evidence of
heart valve damage. If that proportion holds up in larger studies, it
could translate to hundreds of thousands of unsuspecting patients with
valve defects of unknown significance.
Faced with billions of dollars in potential court awards, the drugs'
manufacturers quickly pulled both Redux and fenfluramine,
trade-named Pondimin, off the market in this country, Canada,
Mexico, and France.
In the aftermath of this latest diet pill debacle, big questions linger.
One set involves the role of the US Food and Drug Administration.
Did the FDA slip up in approving Redux? An advisory panel voted
6-5 in late 1995 to recommend approval, but some scientists say the
vote might have tipped the other way if there had been full
consideration of concerns about a rare, fatal lung complication called
primary pulmonary hypertension, and animal studies demonstrating
brain damage from serotonin-raising drugs.
Two neuroscientists who testified before the FDA panel said on
Friday that their findings in multiple animal species, including three
monkey species, demonstrated that both Redux and Pondimin
destroyed serotonin nerve endings in the brain. While Interneuron
officials say that the animal studies involved doses of Redux far higher
than humans would get, the scientists insist the doses were
comparable.
As it happened, not all the panel members heard the neuroscientists'
presentations. During the meeting when the committee narrowly voted
to recommend approval of Redux, ``we weren't there,'' said Lewis
Seiden of the University of Chicago. ``At least two panel members
never heard our side. If they had, I think it might very well have tipped
the balance.''
Some observers say neither the FDA nor the drug manufacturers can
be faulted for not examining the possibility of heart valve damage. No
one suspected that possibility until earlier this year, when a technician
in Fargo, N.D., noticed heart defects in several women taking diet
pills.
But Dr. George Ricaurte of Johns Hopkins University Medical
School, a neuroscientist who presented data on animal brain damage
from Redux, said that if more rigorous human studies had been
conducted on pulmonary hypertension among Redux patients, heart
valve problems might have been picked up by the same test, called an
echocardiogram, that would have been used to look for thickening of
the pulmonary artery.
``If an effort had been made to study humans given Redux to see if
they developed signs of serotonin neurotoxicity, they probably would
have received echocardiograms because we were already aware of
primary pulmonary hypertension,'' Ricaurte said. ``No responsible
study would have neglected to do echocardiograms.''
Interneuron is expected to challenge the data implicating Redux in
heart-valve damage. In a mailing to physicians last week, the company
noted that only 20 of the 291 diet-pill patients tested for heart valve
abnormalities were taking Redux, and only six of those had evidence
of damage. Only two of the six, the company noted, were taking
Redux alone, as opposed to Redux along with phentermine.
Wurtman declined to be interviewed, but he intimated in an e-mail
message that Redux will be exonerated. ``The story isn't over yet,'' he
wrote. ``Let's wait awhile and see if the hypothesized relationship
between Redux, per se, and valvular damage holds up.''
Even if the FDA had stalled Redux approval and asked for further
testing, many say that would not necessarily have forestalled
heart-valve problems. After all, the fen/phen combination was even
more widely used, and it involved two drugs marketed for years but
never authorized for combined use. No federal law prohibits doctors
from using any approved drug for any purpose they choose, or in any
combination.
The idea that serotonin-raising drugs could aid weight reduction took
off in the past two years. Larry Sasich, a drug specialist at the
consumer watchdog group Public Citizen, notes that Pondimin was the
84th most frequently prescribed drug in 1995, but last year jumped to
26th.
Millions of Americans became fen/phen users, often encouraged by
doctors who weren't particular about patients' motives for wanting the
drug or their risk factors. Dr. Pietr Hitzig, a Maryland obesity doctor
who says he has supplied fen/phen to 8,000 patients, said in an
interview that he can tell from a telephone conversation if a patient has
what he calls a ``serotonin-dopamine imbalance.''
``I interview them thoroughly,'' Hitzig said. ``I do not need a body
here to evaluate their status.''
Thus, one lesson from the recent diet-pill episode - if one were
needed - is that any such drug will inevitably be prescribed widely and
casually, no matter what the FDA and manufacturers say about
restricting its use to certain severely obese patients after careful
screening. A corollary is that any unanticipated side effect will be
greatly amplified.
To some experts, that implies the need for greater FDA vigilance for
side effects that emerge after a drug is on the market, or when existing
drugs are put to new, untested uses. Currently, the FDA spends only
about $140,000 a year on MedWatch, its voluntary program for
side-effect reporting by physicians and companies.
In fact, the agency did receive five reports of heart valve problems
among diet-pill users in 1996, the Associated Press reported last
week. But officials failed to notice the pattern, which would have
alerted them to the problem a year earlier.
``We need to get all these issues out on the table,'' said Dr. Louis
Lasagna, a pharmaceutical policy expert at Tufts University. ``It's so
depressing that this happens after years of neglecting obesity as a
public-health problem. It looked as if we were on the road to a logical
approach, which included long-term administration of drugs when
necessary, because dietary and exercise advice don't work.''
What effect will the whole affair have on the future of obesity drugs?
``Wait until it dawns on physicians and patients that there is no longer
any drug available to treat, for example, the 15-million-plus
adult-onset diabetics, 80 to 90 percent of whom are obese and would
either be strongly helped or cured by weight loss,'' Wurtman said.
No one needs to spell out the implications for Anita Goldberg, a
53-year-old Springfield nurse who has relied on fen/phen to take off
about 30 pounds and maintain her weight. The weight loss has
dramatically improved her diabetes control, blood pressure, and
cholesterol - serious matters for a woman whose mother died at 44
from high blood pressure and whose father died at 62 from diabetes.
Goldberg is worried about how she will keep her weight down without
fen/phen. If scientists develop a better drug, she said, ``I'll be one of
the first in line to try it.''
She shouldn't hold her breath. There are some other weight-loss drugs
in the pipeline, but they may face a tougher road now. Several Wall
Street analysts said the withdrawal of Redux and Pondimin will have a
chilling effect on other diet drug developers who face greater FDA
scrutiny and public uncertainty.
One drug, called Meridia, from Knoll Pharmaceutical Co., is expected
to undergo further FDA scrutiny since it works like Redux in raising
serotonin levels. Another drug, Xenical, which blocks the absorption
of 30 percent of the fat a person consumes, was withdrawn from FDA
marketing consideration last month, after its developer, Roche Holding
Ltd., said it needs more time to prove to the FDA that there are no
links between the drug and breast cancer.
The massive litigation emerging from the Redux and Pondimin
experience will likely exert an effect for years to come. Several
lawyers said they expect scores of lawsuits to be filed in the coming
weeks, making claims that the decision to withdraw the drugs came
months after the companies were informed last March of potential
heart valve problems.
Doctors, too, are being swept into the litigation fervor building around
the diet-pill fiasco. Some of them, who say they used the drugs
cautiously, resent colleagues who pushed the pills indiscriminately.
``I don't mind Dick Wurtman making all the money on that drug,'' said
Dr. Harold Solomon, an obesity specialist at Beth Israel Deaconess
Medical Center. ``But I don't want to have to lose sleep because he
invented a drug, the FDA approved it, I prescribed it properly, and
now I'm getting sued because the patient has a heart valve problem
that I had no way to see was coming.''
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(The Boston Globe web site is at globe.com )
NYT-09-23-97 1157EDT< |
