Pill Pushers: How the drug industry abandoned science for salesmanship

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[sSRI-Research] Forbes Magazine - Pill Pushers: How the drug

industry abandoned science for salesmanship

 

 

 

Forbes Magazine

 

http://www.forbes.com/forbes/2006/0508/094a_print.html

 

On The Cover/Top Stories

 

Pill Pushers

 

Robert Langreth and Matthew Herper 05.08.06

 

How the drug industry abandoned science for salesmanship.

 

Novartis employs some of the best medical researchers in the world,

and they have created such lifesavers as Gleevec, which treats a

deadly form of leukemia. But what is the fourth-biggest seller in the

Novartis medicine cabinet? No lifesaver. It's Lamisil, a pill

for--horrors!--toenail fungus. The main effect of the fungus is that

it turns the toenail yellow; it can hurt, but no one has died of this

inconvenience. But a few people may have died taking Lamisil. Federal

regulators have linked the drug to 16 cases of liver failure,

including 11 deaths. Novartis says most of the patients had

preexisting illnesses or were also on other drugs.

 

Yet 10 million Americans have taken Lamisil, which costs $850 for a

three-month treatment. They have been lured by a grotesque cartoon

creature called Digger the Dermatophyte, a squat, yellow fellow with a

dumb-guy New York accent. In TV ads he lifts a toenail as if it were

the hood of a car, then creeps beneath it to declare, " I'm not leavin'! "

 

TNS Media Intelligence calculates that Novartis has spent $236 million

on Lamisil ads in three years (Novartis says it has spent only $100

million). The first run, which featured Digger being crushed by a

giant Lamisil tablet, so overstated the drug's benefit that regulators

objected and the company had to pull the spots; the drug fully cures

the problem in only 38% of patients. But the ad blitz undeniably was

effective: Lamisil sales jumped 19% to $1.2 billion worldwide in 2004

and held steady last year.

 

Lamisil's rise points up what is wrong with the drug industry today:

the triumph of salesmanship over science. The industry spends a

fortune to create and sell a raft of me-too remedies aimed at quelling

sometimes trivial maladies, even as research pipelines run dry,

patents on old drugs expire and critical areas of medicine go

underserved. Sometimes the marketing improves health; Americans would

probably be better off if more of them were hounded into taking pills

to lower cholesterol and blood pressure. Sometimes the result is the

reverse, as when side effects from an overhyped and overprescribed

medicine are fatal.

 

" The dominance of marketing over research has done real damage to

company pipelines, " says Jurgen Drews, former research chief for

Roche. A decade ago he predicted a research slump; it has arrived. A

total of 87 major drugs with $31 billion in combined annual sales have

lost patent protection since 2002, but new drugs aren't arriving fast

enough to replace them. Only 20 were cleared by the Food & Drug

Administration last year, down from 53 a decade ago.

 

 

 

Drugmakers, says Maryland psychiatrist Jack E. Rosenblatt, editor of

Currents in Affective Illness, " don't seem to realize that this is not

toothpaste or shampoo, that they are dealing with something that can

really hurt people. "

 

The industry's malaise is certainly visible on Wall Street. The ten

largest drugmakers have lost $130 billion in combined market value in

two years, a 12% decline at a time when the S & P 500 Index is up 12%.

They have endured scandal after scandal over drug safety and dubious

sales practices. A total of 17 drugs have been recalled in the past

decade. Wyeth's withdrawal of diet drug Redux in 1997 led to $22

billion in damages and counting (FORBES, Apr. 10).

 

Vioxx could yet eclipse that. Merck's new-generation

painkiller--touted to consumers at a cost of $550 million over five

years--was recalled in September 2004 when a study showed that

patients on it for 18 months had double the risk of heart attacks. In

the ensuing legal onslaught 10,000 suits have been filed, seeking

billions in damages and accusing the company of misleading doctors and

the feds. Last month Merck lost a $13.5 million verdict to one heart

attack survivor, its second defeat in five cases tried. There are more

potential lawsuits lurking where these came from.

 

The drug industry, of course, rejects the criticisms. Novartis says

its Lamisil spending " absolutely " " in no way " has taken away resources

from research into more serious diseases and that it spends far more

on its cancer drugs. " Absolutely, marketing doesn't trump

science--this is a science-driven industry, " says Scott Lassman, a

lawyer for Phrma, the industry trade group. He says makers have taken

steps to curb any excesses and give ads a " more sober tone. " Pfizer

research chief Martin Mackay says, " We are thought of as monsters, but

I don't know of a single case where we have been driven to take risks

on a compound because of a marketing push. I would not let it happen. "

 

Says Bristol-Myers Squibb Chief Executive Peter Dolan: " The biggest

disconnect for me is between how the industry is portrayed and how

people in it actually feel about what they do. "

 

Yet Big Pharma's focus on marketing is undeniable, and it spends

hugely on it. The top ten drug firms invest $42 billion a year on

research, 14% of sales--yet they plow more than twice that much into

marketing and administration. In a decade drug firms have almost

tripled the ranks of salespeople calling on physicians, to 100,000,

according to Verispan. That's one seller for every 9 docs; in 1996 it

was one for 18. Often they encourage unauthorized off-label uses or

sponsor " continuing medical education " sessions to stoke more

prescriptions and broaden a drug's patient base.

 

 

--

 

Even the research lab is more marketing-driven than ever. More than $9

billion a year in research spending goes to clinical trials of drugs

that are already approved or may soon be--often to snare new ad

slogans. That is up 90% in four years, says Goldman Sachs. Some of

these ad-driven trials are skewed to pit the sponsor's full-strength

product against a weaker dose of a rival pill. Yet drugmakers have

failed to begin two-thirds of the 1,200 post-marketing trials required

by the FDA.

 

The slogan-geared trials provide fodder for an explosion in consumer

advertising of drugs, which had been highly restricted for decades

before rules were eased in the 1990s. Ad spending in the U.S. has

soared eightfold in nine years to $4.8 billion, says Nielsen

Monitor-Plus, TV spots ply supposed low-risk, quick fixes to millions

of people: Try Zoloft to get happy; gobble a state-of-the-art pain

pill when aspirin would work fine. Drugs designed for narrow sets of

patients end up in the hands of a far broader audience.

 

" It creates demand where there's not even disease there, " complains

internist Robert Centor of the University of Alabama. Drug giants " do

it in a devious way, " he says. " I wish they didn't spend all that

money on marketing. "

 

Merck's marketing of the painkiller Vioxx was, in retrospect, all too

successful, contributing to the multibillion-dollar liability now

looming over the company. Vioxx, part of a new class of drugs known as

COX-2 inhibitors, had been intended for only the small slice of

patients who can't stomach aspirin. But it ended up in the hands of 20

million people, driven by ad spending of $550 million in five years,

says ad tracker TNS. Some spots had 1970s Olympic figure skater

Dorothy Hamill twirling on the ice.

 

Vioxx's chief rival, Celebrex from Pfizer, also reached a far broader

market because of splashy ads. About 60% of patients on the drugs had

low ulcer risk and might have fared just as well on older generics,

say researchers at the University of Chicago and Stanford. Pfizer says

most gastrointestinal complications occur in patients who are not at

high risk.

 

" People would come in asking for--demanding [a COX-2 inhibitor]--and

sometimes threaten to find a new doctor if I didn't prescribe it, "

says physician John Abramson, a clinical instructor at Harvard Medical

School who has consulted for plaintiff lawyers. " Vioxx wasn't a bad

drug for everyone, it was a bad drug for certain patients, " says Chris

D. Robbins of Arxcel, which consults to pharmacy benefit managers.

" Unfortunately, people saw the ads and started demanding the drugs

from their doctors. "

 

TV ads for prescription drugs were rare until Aug. 12, 1997, when the

FDA lifted restrictions to let spots run without lengthy disclaimers

of nasty side effects. Three days later Schering-Plough began a

prime-time campaign for its antihistamine Claritin, featuring smiling

folks frolicking in hay fields to the tune of Irving Berlin's " Blue

Skies. " Schering upped the ante in 1998 with one of the first

celebrity pitches, by TV personality Joan Lunden. Claritin sales

climbed 50% in 1997 and 30% more in 1998, hitting $2.3 billion.

Schering's stock-market value approached $90 billion by mid-1999.

Claritin lost patent protection in 2002. No problem: Schering was

ready with Clarinex, a look-alike successor that still brings in $646

million in annual sales, even though its predecessor is sold

over-the-counter at one-tenth of the price. The shift didn't help

enough: Schering had a mediocre pipeline, and today its market cap is

down by two-thirds to $27 billion.

 

Other companies followed with ads for antidepressants, heartburn

drugs, painkillers and impotence pills. Pfizer found its erectile

dysfunction pitchman in Senator Bob Dole, then age 75. Wall Street

cheered the changes. " We had the whole financial community focused on

blockbusters and maximizing the revenues and aggressive marketing, "

says Daniel Vasella, chief executive of Novartis, which TNS Media

Intelligence says has spent $235 million in three years advertising

Zelnorm. (Novartis disputes the amount.) The drug, which treats

irritable bowel syndrome, costs $200 a month.

 

In the rush to find big sellers, many companies fell into a herd

mentality and focused on the same few common ailments, says Genentech

Chief Arthur Levinson. " Everyone was doing the same thing, so the

chances of success got smaller and smaller. " Big Pharma " said we were

nuts " to test a cancer drug that targeted only 25% of breast cancer

patients, Levinson recalls. Now the drug, Herceptin, is near $1

billion in annual sales. " If you are developing novel drugs, you don't

need sales forces of tens of thousands. "

 

Some drug firms stopped researching in critical areas even as they

focused on pop pills. Eli Lilly & Co. had dominated the antibiotic

field for decades, and new remedies are badly needed to kill

drug-resistant superbugs. Yet in the 1990s the company sold off three

promising antibiotics and antifungals, two of which went on to win

approval. Lilly exited antibiotic research entirely in 2002, believing

the chances of success were higher with antivirals. The next year

Lilly and partner Icos spent $243 million launching their me-too pill

for erectile dysfunction, Cialis. Barry Eisenstein, who headed Lilly's

antibiotic program from 1992 to 1996, says drugs for chronic

conditions, like Prozac, are seen as " a much better and easier

business proposition. " Lilly says that any contention that it didn't

pursue antibiotics to chase mass-market blockbusters is simply not valid.

 

The " easiest profits " come from me-too drugs, says John Santa, medical

director at Oregon Health & Science University. Genuine discovery is a

risky business, " more like drilling for oil. " Instead of prospecting

for real cures, some companies repackage old drugs with the minimal

tweaks needed to get a new patent. Then they stage exhaustive trials

aimed at unearthing some slender advantage that can be cited in

advertising.

 

 

--

 

One throwback, the Lunesta sleeping pill from Sepracor that came out

early last year, is based on a remedy first approved in Europe two

decades ago. It is very similar to Ambien, which is made by

Sanofi-Aventis and racks up U.S. sales of $1.6 billion annually (on an

ad budget of $130 million). Lunesta garnered $330 million in sales in

its first nine months on the market thanks to TV spots featuring a

diaphanous cartoon butterfly flitting in and out of moonlit bedrooms.

Tagline: " Leave the rest to Lunesta. " Sepracor spent $215 million last

year advertising Lunesta, says TNS.

 

To differentiate Lunesta from Ambien, Sepracor tested its drug versus

a placebo in 1,600 patients for six months, something Ambien's maker

hadn't bothered to do. The trials let Sepracor claim in print ads that

Lunesta " is the first and only hypnotic approved for long-term use. "

 

Prescriptions for sleeping pills are up 48% in five years to 43

million prescriptions annually, driven by the huge ad spending for

Ambien and Lunesta. Sales are up 140% in the same period to $2.76

billion. Yet the newer drugs " are no better than older ones costing

about one-tenth as much, " says John Abramson of Harvard. " Has insomnia

become an epidemic in the past five years? Or are the makers

skillfully leading Americans [to] an expensive drug? " he asks.

Sepracor points to an Institute of Medicine report highlighting

insomnia as a serious problem.

 

Astrazeneca, faced with patent expiration on its blockbuster for acid

reflux, Prilosec--touted as " the purple pill " --tweaked it a bit to

create " the new purple pill, " Nexium. AstraZeneca studied high doses

of Nexium in five trials totaling 12,000 patients. All this to show

the drug helped the esophagus heal in an extra one in 20 patients,

compared with Prilosec or competitor Prevacid.

 

The payoff: Nexium now is touted as " the healing purple pill, " hawked

in ubiquitous TV spots. In one, a sterling-haired man in black cites

the " exciting news " from one of the studies and concludes, " Better is

better. " Nexium is the third-best-selling drug in the world, according

to IMS Health, with $5.7 billion in sales and an ad budget of $226

million last year. Never mind that some of the trials were stacked: In

three of the big trials AstraZeneca pitted high doses of Nexium versus

half the dose of Prilosec; it never bothered to test whether twice the

Prilosec dose would be equally effective. AstraZeneca says there are

" clear differences " between the two purple pills and notes that one

equal-dose study showed a statistical advantage for Nexium in

esophageal healing.

 

In another instance AstraZeneca staged trials that fizzled but used

them for a new ad claim anyway. Before it won approval in August 2003,

AstraZeneca studied its Lipitor look-alike, Crestor, for cholesterol

reduction, in 24,000 patients, hoping to prove superiority. But the

only dose of Crestor that clearly beat Lipitor turned out to cause

kidney problems and never won fda approval. Nonetheless, after

Crestor's debut AstraZeneca used ads featuring a voiceover by the

stentorian actor Patrick Stewart of Star Trek: The Next Generation, in

Seussian rhyme: " When Crestor performed in a head-to-head test, its

lowering effect was clearly the best. "

 

That claim brought a rebuke from the FDA in March 2005. The company

halted the ads, but it now is testing Crestor in 30,000 more patients.

AstraZeneca notes that Crestor is the only statin shown to clear

plaque out of the arteries.

 

The drug industry has begun to restrain its own advertising. Last June

Bristol-Myers Squibb took a first step, announcing that it would wait

a year after drugs hit the market to begin running ads, leaving time

for doctors to learn about a medicine and for side effects to crop up.

Companies are now submitting ads to the FDA before they run and are

more clearly stating big risks.

 

But myriad drugmakers have plenty of ways to game the system. In the

market for new schizophrenia treatments Lilly and Johnson & Johnson

and others have run 21 head-to-head trials--and 90% of the time the

conclusions favor the sponsor's drug, according to research in the

American Journal of Psychiatry. Nine studies compared Lilly's Zyprexa

to Johnson & Johnson's Risperdal. All five Lilly-paid trials favored

Zyprexa; three of four J & J studies favored Risperdal. Lilly stands by

its high scientific standards and says the results highlight the need

for more independent studies. Another analysis, in Archives of

Internal Medicine, tallied 56 studies of painkillers; not once was the

sponsor's drug deemed inferior.

 

" The comparative studies are a joke. They are comical. A lot of the

scientific literature these days is worthless, " says psychiatrist Jack

E. Rosenblatt. " The whole process has been corrupted, " says British

bone researcher Aubrey Blumsohn. " It is getting worse as the financial

stakes are rising. "

 

 

--

 

Blumsohn contends procter & gamble for years refused to supply raw

data for a 2003 study he led comparing its drug Actonel to Merck's

competing drug, Fosamax, even after he became suspicious that

Procter's analysis was skewed in favor of Actonel. " It was a process

of intimidation, " says Blumsohn, who was suspended from his job at the

University of Sheffield after he complained to the British press. (He

recently left after agreeing to an undisclosed settlement.) Procter &

Gamble says it " always " provided Blumsohn with " unfiltered access to

all of the data that was relevant. " " This issue is about a

relationship fraught with misunderstanding, and we regret that, " a

spokesman says. Procter is now providing Dr. Blumsohn with additional

data.

 

Despite the profusion of dubious trials, drugmakers often don't

conduct crucial studies to ensure new drugs are truly safe as they

move out to a mass market. This year Trasylol, a Bayer drug used to

prevent bleeding during heart surgery, has emerged as yet another

problem medication. In December Bayer promised annual sales of the

drug, then at $280 million, would surge to $600 million.

 

But a study of 4,000 surgery patients found that the drug, at $1,400

per dose, posed more than twice as much risk of kidney failure as

cheaper generic alternatives, as well as more heart attacks and

strokes. Replacing Trasylol with generics would prevent 10,000 cases

of kidney failure each year, says clinical researcher Dennis Mangano,

who led the study at the nonprofit Ischemia Research & Education

Foundation in San Bruno, Calif.

 

Bayer says its own studies of 6,500 patients haven't found any link

between the drug and kidney failure, heart attack or stroke, and that

it is working with the FDA to evaluate the Mangano report and another

study linking the drug to serious adverse events. " Bayer's highest

priority and concern is patient safety, " says a spokeswoman.

 

Mangano, who also did the first study to raise concerns about the

cardiovascular risk of Pfizer's Bextra (pulled from the market in

April 2005), spent $35 million of his foundation's endowment to

painstakingly gather the Trasylol data over four years. Few

independent researchers have the money to perform such definitive

safety studies. His foundation used to do clinical trials for the

industry, but drug companies don't call much anymore, he says. " There

is no incentive for companies to find problems with safety once a drug

is approved. It is just downside risk, " he says. The result is

worrisome: " We find out a drug is unsafe when the bodies accumulate. "

 

 

 

 

I Just Play One On TV...

Since drug advertising restrictions were eased in 1997, several

campaigns have raised eyebrows and ire. Click here to see some of the ads.

 

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