By Neil Swidey
[Part 1, Part 2]
The heartburn drug Nexium, the object of a half-billion-dollar marketing campaign to move people off the prescription medications predecessor, Prilosec
Top 10 Pharmaceuticals
Prilosec slipped from the number-one to the number-two selling prescription drug last year after its patent was about to expire and maker AstraZeneca shifted its promotional muscle to the "new Purple Pill," Nexium.
The Life Cycle of the Purple Pill
Worldwide earnings from the Purple Pill grew annually from the time it was introduced in 1988 until just before its patent expired last year.
Gertrude was sittingwith her husband in their Lowell living room, watching thenightly news, when the man on the moving cliff found her duringa commercial break. "I'm every man," the serious,gray-haired guy said, nodding confidently. "And everywoman," continued a blonde standing on the adjacent cliff,"whoever suffered from frequent, persistent heartburn."Over the course of 60 seconds, waves crashed, sunlight pushedthrough an overcast sky, and rock formations reconnected hydraulically.A dozen cliff-top baby boomers of every race spread the wordabout Nexium, as capsules of "the new Purple Pill"rained from the heavens.
Like most of theTV commercials for prescription drugs that keep Brokaw, Rather,and Jennings on the air every night, the Nexium spot endedwith the suggestion "Talk to your doctor." But Gertrudedidn't have to. Her primary care physician had already broughtup Nexium with her at her last visit. "Hey, that's thedrug my doctor just switched me to," she told her husband."It must be pretty good."
The 79-year-old,who didn't want her last name used, is a longtime suffererof serious heartburn. So she's among the many who hail themiracle powers of the original Purple Pill, Prilosec. Thatdrug stripped misery from the lives of millions and becamethe world's best-selling prescription drug - and the numberone medication prescribed for seniors - taking in $6billion a year. Prilosec is so good, and patientsso attached to it, that doctors jokingly call it "purplecrack."
It's an expensivehabit, about $4 for each daily pill,or $1,500 a year. General Motors alone spent $55 million onPrilosec for its workers last year. The drug has been theultimate cash cow for its maker, AstraZeneca.
But by now thecow should have run dry. The main patent on Prilosec expiredmore than a year ago. Under normal circumstances, that wouldhave triggered the arrival of a generic version on the market,followed by a host of generic rivals. With so much low-costcompetition, we would all be enjoying lower drug costs. Butthat didn't happen.
Through lawsuits,the makers of Prilosec have managed to keep the generics atbay while unleashing a half-a-billion-dollar marketing blitzto move people off Prilosec and onto Nexium, their costly,patent-protected new Purple Pill, which even their own studiesshow to be barely more effective than the original.
How and why AstraZenecahas been able to keep the purple profits flowing sheds morelight on the nation's prescription drug crisis than reamsof policy papers and congressional testimony. The same tacticsare being used by just about all the big pharmaceutical companies,which are under intense shareholder pressure to maintain theirbest-in-business profits as the patents on about 20 blockbusterdrugs expire over the next couple of years.
That explains theads for the new drug Clarinex that are everywhere, right downto the white CVS bag your last prescription came in. Schering-Ploughhas been feverishly working to move the itchy-eyed onto Clarinexand off its omnipresent Claritin, whose patent expires thismonth. Ditto for Forest Laboratories' new antidepressant,Lexapro, the spawn of Celexa, whose patent is set to expireat the beginning of 2004.
But given the sheernumbers involved and its still-evolving nature, the PurplePill may be our best case study of the forces driving up prescriptiondrug costs. It's the story of a wondrous medical advance thatbrought relief to millions and significantly reduced the needfor surgery. But it's also the story of the steroid-injectedmarketing muscle that has ensnared, among others, Boston'smost respected hospitals and the exhaustive legal maneuversthat have delayed competition, helping to drive up costs foryou, me, and Gertrude.
"This is alocomotive that's barreling down the tracks, and you eitherget out of the way, get on board, or get squished," saysDr. James Richter, a Boston gastroenterologist.
First things first:This prescription drug crisis you hear everyone squawkingabout - it's really so avoidable. We Americans are on paceto spend nearly $200 billion on ourmeds this year. That's more than the federal governmentpaid last year for education, agriculture, transportation,and the environment combined.
It matches thehighest prediction of what it would cost to topple SaddamHussein with a full-scale attack on Iraq. Talk about a waron drugs. In any rational world, that sum would not just coverour current pill habit but would also allow us to pick upthe drugstore tab for all those senior citizens paying outof pocket for their high blood pressure and arthritis pills.We could spare them the indignity of those Greyhound-bus narc-runsto Canada to score their cut-rate Cardizem and Celebrex.
Who's responsiblefor the fact that prescription drug spending continues torise 15 to 20 percent a year, doubling every five years?
The big pharmaceuticalshave certainly lost much of their "best and the brightest- making life better for you" luster. That's perhapsinevitable when you pour more money into peddling your newestproduct than Nike does its sneakers. But there's plenty ofblame to go around. The government allows drug companies tocontrol the testing of new drugs, designing trials to suittheir interests, not the consumers'.
HMOs and hospitals,under their own bottom-line pressures, make deals that helpthe drug manufacturers move patients to new, expensive drugswhen cheaper, older ones might do fine. Doctors operate ina world where drug maker freebies like Red Sox tickets, FourSeasons dinners, and Arizona golf outings somehow seem normalinstead of the outrageous graft they are.
Now go to yourbathroom and look in the mirror. There's a good chance thatyou're one of those shareholders demanding higher profitsfrom the pharmaceutical companies, even if you don't knowit. (Think about those pharmaceutical-dense mutual funds you'recounting on to pay your kid's college tuition.) Now open themedicine cabinet.
Do you see a bottleof Clarinex? Or maybe there's a vial of Vioxx, the new drugyou pressed your doctor to prescribe for your arthritis, becauseit did wonders for Dorothy Hamill. ("Look how easilyshe can lace up her skates now!") Forget the fact thatseveral studies have questioned whether it's any more effectivethan over-the-counter Advil. Or maybe there's some Viagraon the shelf. And let's just say you're half Bob Dole's ageand haven't been treated for prostate cancer.
"We're inthis perfect storm of forces that conspire to make it a veryexpensive time," says Dr. Thomas Lee, medical directorfor Partners Community HealthCare, the largest physician networkin Massachusetts. He ticks off some of the factors drivingup costs.
First, all thatresearch after World War II didn't begin to bear fruit untilthe 1980s and 1990s. Now we have effective medicines for allkinds of conditions, including ways to treat impotence anddepression that don't involve a couch.
Second, we've gotall these baby boomers passing through middle age and eithergetting chronic disease or doing everything to avoid it. "Babyboomers don't want to accept that they will ever die,"says Lee. Just since 1995, his Partners group has seen a nearlyone-fifth increase in the number of patients taking medicationregularly. And last, we've got pharmaceutical companies tryingto get the maximum market for the drugs they spent so muchto develop. "They're not interested in fine-tuning tomake sure the people who get the new expensive drugs are thosewho will really benefit from it," Lee says. "Theywant everyone for whom there is a reasonable justification."
This is how itused to be: The boss would keep four bottles of Maalox inhis desk. Every three hours, he'd grab one from his bottomdrawer and take a swig. Short of surgery, there wasn't muchelse he could do to treat his heartburn, which is the mainsymptom of gastroesophageal reflux disease.
Food travels fromthe mouth, down the esophagus, and through a sphincter muscleto get into the stomach. Because the stomach is filled withacid potent enough to take the rust off your car, the sphincteris supposed to relax only to let food and drink in. But forthe 25 million Americans who suffer chronic heartburn, themuscle relaxes way too often.
So the acid regularlyflows up into the esophagus, causing a noxious burning inthe upper abdomen and lower chest, especially after eatingthat third slice of deep-dish pepperoni pizza.
In 1977, the Tagametrevolution began. Whereas the common antacids like Maaloxand Tums neutralized acid, prescription Tagamet blocked it.It made a huge difference. Still, there was a group of peoplewho needed something more powerful than Tagamet and its successors,included in a class of drugs that came to be known as H2 blockers.
In 1989, that powercame in spades and in the unforgettable shade of purple. Prilosecwas the first proton pump inhibitor, or PPI. H2 blockers stopacid at one of three possible sites in the cells of the stomach,but PPIs block it at the final site of production. They'rea fail-safe means of turning off the stomach-juice spigotbefore it backs up into the esophagus. "Prilosec gavephysicians a sense of power, a sense that we can cure you,"recalls Dr. James Reichheld, an Andover gastroenterologist.
Still, Prilosecwas really just a niche drug when the Swedish company AstraAB (it later merged with the British firm Zeneca) teamed upwith the US firm Merck to launch it in the United States.The US Food and Drug Administration approved it for just twoindications, or uses, for which there was a particularly limitedpool of customers. Heartburn wasn't one of them. And therewere fears, later shown to be unfounded, that the drug mighthave cancer risks.
As most drug manufacturersdo, Astra continued clinical trials to win approval for newindications to put on the Prilosec label - it eventually reachedeight - and increase its customer base. (Remember, Viagrawas originally developed to treat angina; that whole erectionthing was just a pleasant surprise.)
Prilosec continuedto grow. Then, in 1997, the FDA tied a bow on a big fat giftto the pharmaceutical industry: relaxed rules for drug advertising.It's not that direct-to-consumer advertising was a new phenomenon.
Back in 1708, Bostonapothecary Nicholas Boone bought the first patent-medicinead, announcing in the News-Letter that he would be sellingDaffy's Elixir Salutis for four shillings and sixpence a bottle.It's just that, prior to 1997, drug makers were required todisclose so many side effects on their ads as to make TV spotsunworkable. The new FDA rules allowed them to make their claimsunimpeded, as long as they offered a phone number or Web siteor referenced a magazine ad where consumers could get thefine print.
Prilosec was theperfect drug to market on TV. Millions of people have gastricproblems, and many were no doubt feeling the pain right asthe commercial flashed on the screen in front of them. Herewas this incredibly effective new medication waiting to changetheir lives. And when they later found themselves sittingon a doctor's padded exam table, they didn't even have torecall the drug's name. All they had to remember was its color.
Soon, Purple Pillads were everywhere - on TV, on the Web, even on the floorof New York's bus terminals. Hall of Fame pitcher Jim Palmerwas telling anyone who would listen how the drug had savedhis broadcasting career. All those forces helped catapultPrilosec to the top. In 1998, it became the firstdrug ever to hit $5 billion a year in worldwidesales, and it didn't stop there.
Here's the thing:Unlike many hyped drugs, Prilosec is a wonder drug that actuallydeserves its title. In dozens of interviews for this article,even critics of the purple juggernaut got around to saying:"It's a very good drug." But that doesn't mean aslew of people couldn't do fine on something much cheaper.
Prilosec's successprompted several competitors to come forward with their ownPPIs: Prevacid (TAP/Abbott), Aciphex (Eisai/Johnson &Johnson), and Protonix (Wyeth). And, of course, Prilosec me-too'editself last year with the launch of Nexium.
It's probably notsurprising that me-toos have become so irresistible. Tryingto come up with genuine breakthroughs is a lot harder, riskier,and more expensive. A recent study from Tufts University'sCenter for Drug Development found that it costs an averageof $802 million to develop and win approval to bring a newdrug to market in the United States.
Why so much? Takea drive out to Waltham to AstraZeneca R&D Boston, thecompany's new three-winged structure of Minnesota limestone.Throughout four floors of bright, impeccable labs, sneaker-cladscientists in white coats are on the hunt for genuinely novelmedicines - not me-toos - to treat cancer and infection. Ina field that has come to be dominated by talk of profits andpatents, the vital work going on behind these glass walls- testing and retesting compounds, replicating DNA - putssome of the inspiring sheen back on the pharmaceutical industry.
I ask Hans Nilsson,the Swedish native who oversees the Waltham site, why it'sso hard to hatch a new drug. He walks up to the white boardin his office and makes a series of drawings: enzyme, membrane,cell, tissue, organ, mouse, cat, dog, monkey, human, clusterof humans.
Drug discovery,he says, is the attempt to make a series of increasingly complexconnections to get to the finish line. If the connection worksfrom, say, cell to tissue, you can move on. More often thannot, it won't, so you have to return to an earlier step. Evenat the end, when you've shown a compound to be effective andsafe in thousands of humans, you might get one whose liverfails because of toxicity caused by the drug. So you startagain.
The vast majorityof attempts will never get to the approval stage. The trickis knowing how long to stick with it or when to pack it in.Research on omeprazole, the generic name for Prilosec, "startedin the late 1960s," Nilsson says. "It was launched20 years later. Twenty years. You never know how close youmight be."
BostonGlobe November 17, 2002