By Neil Swidey
|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
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 sitting with her husband in their Lowell living room, watching the nightly news, when the man on the moving cliff found her during a commercial break. "I'm every man," the serious, gray-haired guy said, nodding confidently. "And every woman," continued a blonde standing on the adjacent cliff, "whoever suffered from frequent, persistent heartburn." Over the course of 60 seconds, waves crashed, sunlight pushed through an overcast sky, and rock formations reconnected hydraulically. A dozen cliff-top baby boomers of every race spread the word about Nexium, as capsules of "the new Purple Pill" rained from the heavens.
Like most of the TV commercials for prescription drugs that keep Brokaw, Rather, and Jennings on the air every night, the Nexium spot ended with the suggestion "Talk to your doctor." But Gertrude didn't have to. Her primary care physician had already brought up Nexium with her at her last visit. "Hey, that's the drug 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 sufferer of serious heartburn. So she's among the many who hail the miracle powers of the original Purple Pill, Prilosec. That drug stripped misery from the lives of millions and became the world's best-selling prescription drug - and the number one medication prescribed for seniors - taking in $6 billion a year. Prilosec is so good, and patients so attached to it, that doctors jokingly call it "purple crack."
It's an expensive habit, about $4 for each daily pill, or $1,500 a year. General Motors alone spent $55 million on Prilosec for its workers last year. The drug has been the ultimate cash cow for its maker, AstraZeneca.
But by now the cow should have run dry. The main patent on Prilosec expired more than a year ago. Under normal circumstances, that would have triggered the arrival of a generic version on the market, followed by a host of generic rivals. With so much low-cost competition, we would all be enjoying lower drug costs. But that didn't happen.
Through lawsuits, the makers of Prilosec have managed to keep the generics at bay while unleashing a half-a-billion-dollar marketing blitz to move people off Prilosec and onto Nexium, their costly, patent-protected new Purple Pill, which even their own studies show to be barely more effective than the original.
How and why AstraZeneca has been able to keep the purple profits flowing sheds more light on the nation's prescription drug crisis than reams of policy papers and congressional testimony. The same tactics are being used by just about all the big pharmaceutical companies, which are under intense shareholder pressure to maintain their best-in-business profits as the patents on about 20 blockbuster drugs expire over the next couple of years.
That explains the ads for the new drug Clarinex that are everywhere, right down to the white CVS bag your last prescription came in. Schering-Plough has been feverishly working to move the itchy-eyed onto Clarinex and off its omnipresent Claritin, whose patent expires this month. Ditto for Forest Laboratories' new antidepressant, Lexapro, the spawn of Celexa, whose patent is set to expire at the beginning of 2004.
But given the sheer numbers involved and its still-evolving nature, the Purple Pill may be our best case study of the forces driving up prescription drug costs. It's the story of a wondrous medical advance that brought relief to millions and significantly reduced the need for surgery. But it's also the story of the steroid-injected marketing muscle that has ensnared, among others, Boston's most respected hospitals and the exhaustive legal maneuvers that have delayed competition, helping to drive up costs for you, me, and Gertrude.
"This is a locomotive that's barreling down the tracks, and you either get out of the way, get on board, or get squished," says Dr. James Richter, a Boston gastroenterologist.
First things first: This prescription drug crisis you hear everyone squawking about - it's really so avoidable. We Americans are on pace to spend nearly $200 billion on our meds this year. That's more than the federal government paid last year for education, agriculture, transportation, and the environment combined.
It matches the highest prediction of what it would cost to topple Saddam Hussein with a full-scale attack on Iraq. Talk about a war on drugs. In any rational world, that sum would not just cover our current pill habit but would also allow us to pick up the drugstore tab for all those senior citizens paying out of pocket for their high blood pressure and arthritis pills. We could spare them the indignity of those Greyhound-bus narc-runs to Canada to score their cut-rate Cardizem and Celebrex.
Who's responsible for the fact that prescription drug spending continues to rise 15 to 20 percent a year, doubling every five years?
The big pharmaceuticals have certainly lost much of their "best and the brightest - making life better for you" luster. That's perhaps inevitable when you pour more money into peddling your newest product than Nike does its sneakers. But there's plenty of blame to go around. The government allows drug companies to control the testing of new drugs, designing trials to suit their interests, not the consumers'.
HMOs and hospitals, under their own bottom-line pressures, make deals that help the drug manufacturers move patients to new, expensive drugs when cheaper, older ones might do fine. Doctors operate in a world where drug maker freebies like Red Sox tickets, Four Seasons dinners, and Arizona golf outings somehow seem normal instead of the outrageous graft they are.
Now go to your bathroom and look in the mirror. There's a good chance that you're one of those shareholders demanding higher profits from the pharmaceutical companies, even if you don't know it. (Think about those pharmaceutical-dense mutual funds you're counting on to pay your kid's college tuition.) Now open the medicine cabinet.
Do you see a bottle of Clarinex? Or maybe there's a vial of Vioxx, the new drug you pressed your doctor to prescribe for your arthritis, because it did wonders for Dorothy Hamill. ("Look how easily she can lace up her skates now!") Forget the fact that several studies have questioned whether it's any more effective than over-the-counter Advil. Or maybe there's some Viagra on the shelf. And let's just say you're half Bob Dole's age and haven't been treated for prostate cancer.
"We're in this perfect storm of forces that conspire to make it a very expensive time," says Dr. Thomas Lee, medical director for Partners Community HealthCare, the largest physician network in Massachusetts. He ticks off some of the factors driving up costs.
First, all that research after World War II didn't begin to bear fruit until the 1980s and 1990s. Now we have effective medicines for all kinds of conditions, including ways to treat impotence and depression that don't involve a couch.
Second, we've got all these baby boomers passing through middle age and either getting chronic disease or doing everything to avoid it. "Baby boomers don't want to accept that they will ever die," says Lee. Just since 1995, his Partners group has seen a nearly one-fifth increase in the number of patients taking medication regularly. And last, we've got pharmaceutical companies trying to get the maximum market for the drugs they spent so much to develop. "They're not interested in fine-tuning to make sure the people who get the new expensive drugs are those who will really benefit from it," Lee says. "They want everyone for whom there is a reasonable justification."
This is how it used to be: The boss would keep four bottles of Maalox in his desk. Every three hours, he'd grab one from his bottom drawer and take a swig. Short of surgery, there wasn't much else he could do to treat his heartburn, which is the main symptom of gastroesophageal reflux disease.
Food travels from the mouth, down the esophagus, and through a sphincter muscle to get into the stomach. Because the stomach is filled with acid potent enough to take the rust off your car, the sphincter is supposed to relax only to let food and drink in. But for the 25 million Americans who suffer chronic heartburn, the muscle relaxes way too often.
So the acid regularly flows up into the esophagus, causing a noxious burning in the upper abdomen and lower chest, especially after eating that third slice of deep-dish pepperoni pizza.
In 1977, the Tagamet revolution began. Whereas the common antacids like Maalox and Tums neutralized acid, prescription Tagamet blocked it. It made a huge difference. Still, there was a group of people who 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 power came in spades and in the unforgettable shade of purple. Prilosec was the first proton pump inhibitor, or PPI. H2 blockers stop acid at one of three possible sites in the cells of the stomach, but PPIs block it at the final site of production. They're a fail-safe means of turning off the stomach-juice spigot before it backs up into the esophagus. "Prilosec gave physicians a sense of power, a sense that we can cure you," recalls Dr. James Reichheld, an Andover gastroenterologist.
Still, Prilosec was really just a niche drug when the Swedish company Astra AB (it later merged with the British firm Zeneca) teamed up with the US firm Merck to launch it in the United States. The US Food and Drug Administration approved it for just two indications, or uses, for which there was a particularly limited pool of customers. Heartburn wasn't one of them. And there were fears, later shown to be unfounded, that the drug might have cancer risks.
As most drug manufacturers do, Astra continued clinical trials to win approval for new indications to put on the Prilosec label - it eventually reached eight - and increase its customer base. (Remember, Viagra was originally developed to treat angina; that whole erection thing was just a pleasant surprise.)
Prilosec continued to grow. Then, in 1997, the FDA tied a bow on a big fat gift to the pharmaceutical industry: relaxed rules for drug advertising. It's not that direct-to-consumer advertising was a new phenomenon.
Back in 1708, Boston apothecary Nicholas Boone bought the first patent-medicine ad, announcing in the News-Letter that he would be selling Daffy's Elixir Salutis for four shillings and sixpence a bottle. It's just that, prior to 1997, drug makers were required to disclose so many side effects on their ads as to make TV spots unworkable. The new FDA rules allowed them to make their claims unimpeded, as long as they offered a phone number or Web site or referenced a magazine ad where consumers could get the fine print.
Prilosec was the perfect drug to market on TV. Millions of people have gastric problems, and many were no doubt feeling the pain right as the commercial flashed on the screen in front of them. Here was this incredibly effective new medication waiting to change their lives. And when they later found themselves sitting on a doctor's padded exam table, they didn't even have to recall the drug's name. All they had to remember was its color.
Soon, Purple Pill ads were everywhere - on TV, on the Web, even on the floor of New York's bus terminals. Hall of Fame pitcher Jim Palmer was telling anyone who would listen how the drug had saved his broadcasting career. All those forces helped catapult Prilosec to the top. In 1998, it became the first drug ever to hit $5 billion a year in worldwide sales, and it didn't stop there.
Here's the thing: Unlike many hyped drugs, Prilosec is a wonder drug that actually deserves 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 a slew of people couldn't do fine on something much cheaper.
Prilosec's success prompted several competitors to come forward with their own PPIs: Prevacid (TAP/Abbott), Aciphex (Eisai/Johnson & Johnson), and Protonix (Wyeth). And, of course, Prilosec me-too'ed itself last year with the launch of Nexium.
It's probably not surprising that me-toos have become so irresistible. Trying to come up with genuine breakthroughs is a lot harder, riskier, and more expensive. A recent study from Tufts University's Center for Drug Development found that it costs an average of $802 million to develop and win approval to bring a new drug to market in the United States.
Why so much? Take a drive out to Waltham to AstraZeneca R&D Boston, the company's new three-winged structure of Minnesota limestone. Throughout four floors of bright, impeccable labs, sneaker-clad scientists in white coats are on the hunt for genuinely novel medicines - not me-toos - to treat cancer and infection. In a field that has come to be dominated by talk of profits and patents, the vital work going on behind these glass walls - testing and retesting compounds, replicating DNA - puts some of the inspiring sheen back on the pharmaceutical industry.
I ask Hans Nilsson, the Swedish native who oversees the Waltham site, why it's so hard to hatch a new drug. He walks up to the white board in his office and makes a series of drawings: enzyme, membrane, cell, tissue, organ, mouse, cat, dog, monkey, human, cluster of humans.
Drug discovery, he says, is the attempt to make a series of increasingly complex connections to get to the finish line. If the connection works from, say, cell to tissue, you can move on. More often than not, it won't, so you have to return to an earlier step. Even at the end, when you've shown a compound to be effective and safe in thousands of humans, you might get one whose liver fails because of toxicity caused by the drug. So you start again.
The vast majority of attempts will never get to the approval stage. The trick is knowing how long to stick with it or when to pack it in. Research on omeprazole, the generic name for Prilosec, "started in the late 1960s," Nilsson says. "It was launched 20 years later. Twenty years. You never know how close you might be."
Boston Globe November 17, 2002