COMMERCIAL: If you have arthritis pain, there's reason to celebrate. It's Celebrex.
SUSAN DENTZER: This upbeat commercial sings the praises of one of the best-selling prescription drugs on the market.
COMMERCIAL: Celebrate. Come on and celebrate.
SUSAN DENTZER: And no one is celebrating as much as the drug's manufacturer, Pharmacia Corporation. Last year Celebrex became the first prescription drug to rack up $1 billion in sales in its first year on the market. Global sales to date have topped $3 billion. Now Celebrex is locked in a tight race with another new arthritis drug, Vioxx, made by pharmaceutical giant MERCK.
COMMERCIAL: All I really want is to be able to climb the stairs and give Michael a bath.
COMMERCIAL: Vioxx is here.
SUSAN DENTZER: Since their debut in 1999, these two drugs have come to account for 40 percent of all U.S. prescriptions for so-called anti-inflammatory drugs and nearly 60 percent of dollar sales in that category.
HEMANI SHAH, Securities Analyst: This has a potential of becoming something on the order of maybe a total of $10 billion, maybe four or five years down the road. So it is a very, very important market for the pharmaceutical industry.
SUSAN DENTZER: It's also an important case study in today's health care economics. Higher prescription drug spending now accounts for about half the annual increase in the nation's health costs. That's in part because drugs like Celebrex and Vioxx can cost up to ten times as much as the older medications they're designed to replace. At the same time, there's considerable debate over how much more effective these drugs are than older medications. And some critics charge that pharmaceutical companies are overselling the benefits of these drugs, in part through advertising aimed directly at consumers. The story of how Celebrex and Vioxx came to dominate the arthritis drug market began about a decade ago. Researchers were looking for ways to relieve the joint pain and inflammation that afflicts arthritis sufferers around the world-- 43 million of them in the U.S. Alone. Traditionally, arthritis patients have treated their pain with medications known as non-steroidal anti-inflammatory drugs, or NSAIDS. Among them are the familiar aspirin and ibuprofen.
DR. ROGER PERLMUTTER, MERCK Pharmaceuticals: Non-steroidal anti- inflammatory drugs all work by inhibiting enzymes called cycloxgenases, and we refer to those for simplicity as Cox enzymes.
SUSAN DENTZER: Dr. Roger Perlmutter oversees basic research at MERCK. He says researchers originally believed there was only one Cox enzyme, but then discovered in the early 1990s that there were two. The first, Cox-1, was actually a kind of good Cox that played a role in protecting the lining of the stomach and intestine. The second, Cox-2, was a bad Cox that produced substances called prostaglandins that triggered inflammation and pain. But conventional NSAIDs like ibuprofen actually switched off both the good and bad Cox enzymes. That produced dangerous and even deadly side effects in about 4 percent of patients on NSAIDs, including bleeding in the stomach or intestine.
DR. ROGER PERLMUTTER: The result is an increase in ulceration and severe gastrointestinal complications. Each year something in excess of 8,500 deaths and more than 50,000 hospitalizations result from the chronic use of non- steroidal anti-inflammatory drugs.
SUSAN DENTZER: That prompted researchers to develop a new class of drugs to minimize dangerous side effects. These medications were designed to switch off Cox-2 but not Cox-1, and as a result, were called Cox-2 inhibitors. First to enter the multi- million-dollar race was GD Searle, a company since absorbed by Pharmacia. Its drug, Celebrex, went on the market in January 1999, followed several months later by Vioxx. Millions of patients like Bob Dahlquist started taking the drugs. A 66-year-old contractor, he was diagnosed three years ago with rheumatoid arthritis.
BOB DAHLQUIST: I went to bed, woke up the next morning, I couldn't get out of bed. I had pains in my hip. It seemed like every joint had a needle or a razor blade or sandpaper or something in it.
SUSAN DENTZER: After several months of treatment with ibuprofen, Dahlquist developed early-stage ulcers in his small intestine. Fearing he could bleed to death, his physician switched Dahlquist to Vioxx and later, to Celebrex.
BOB DAHLQUIST: I started the Celebrex in June, and now three or four months later, I feel, as I say, 99.9 percent restored.
SUSAN DENTZER: Meanwhile, many doctors also began prescribing the drugs for patients like Linda McDermid, a marathon runner in her mid-40's. She has suffered from occasional short-term acute pain caused by her sports injuries.
LINDA McDERMID: I was experiencing some pain in my lower leg, between the calf and the Achilles. Eventually I did go to see my physician and he gave me some samples of Vioxx to try, and that worked; worked quite well.
SUSAN DENTZER: The pharmaceutical companies lost no time trumpeting such apparent success stories.
SPOKESMAN: We believe that the data has already shown that Celebrex is unprecedented in its efficacy in treating the signs and symptoms of rheumatoid arthritis and osteoarthritis.
SUSAN DENTZER: But in fact, say a number of experts, the data didn't demonstrate that at all. Thomas Moore is a health policy analyst at George Washington University. He reviewed the results of clinical trials of the drugs sponsored by the two companies. Among other things, the trials examined how well Celebrex and Vioxx performed in relieving chronic pain caused by the most common form of arthritis, osteoarthritis.
THOMAS MOORE, George Washington University: They provided roughly-- never more-- but roughly the same amount of pain relief for arthritis sufferers that you would get again from aspirin, ibuprofen or naproxen.
SUSAN DENTZER: In fact, Moore notes, some patients hardly experienced any relief.
THOMAS MOORE: About two-thirds or more reported they either felt the same as before they took the medicine, or worse. About one-third reported that they were better.
SUSAN DENTZER: At the same time, patients who did get relief sometimes experienced mild side effects like stomach upset. But there was an even bigger disappointment about the Cox-2 drugs. Although the drugs had been designed to produce fewer dangerous side effects, like gastrointestinal bleeding, clinical trials actually produced inconclusive results on that score. As a result, officials here at the federal Food and Drug Administration refused to allow the companies what they'd been seeking all along: The ability to claim on their so-called drug labels-- the information given to doctors-- that the drugs really were safer than conventional NSAIDs. Despite that setback, the Cox-2 drugs had some important forces working for them. One was an arthritis market desperate for relief. Another was the prowess of the drug companies at introducing their products to doctors and patients.
THOMAS MOORE: They literally leave no stone unturned. They contact with repeated occasions literally every doctor in the country who might prescribe it.
SUSAN DENTZER: According to the drug-tracking firm IMS Health, Pharmacia and MERCK also gave away 25 million free samples of Celebrex and Vioxx in the first nine months of 2000. That was more free medicine that was handed out than in any other class of medication on the market. Cindy Parks Thomas studies prescription drug trends at Brandeis University.
CINDY PARKS THOMAS, Brandeis University: Giving out samples is a very powerful marketing tool. When you start, it's nice for a physician to be able to say, "Try these and we'll continue." So the patient has little risk, little financial risk starting a new medication.
COMMERCIAL: You may be able to plan your day around your life instead of your pain.
SUSAN DENTZER: The companies have also spent tens of millions of dollars on direct-to-consumer advertising, as in this commercial for Vioxx, the most heavily advertised drug during 2000. Pharmaceutical company officials say all this marketing is being done in patients' best interests.
COMMERCIAL SPOKESPERSON: Vioxx.
SUSAN DENTZER: Dr. Steve Geis is vice president of clinical research at Pharmacia.
DR. STEVE GEIS, Pharmacia Pharmaceuticals: We are very committed to ensuring that physicians and the patients know about Celebrex, how effective it is, how safe it is, so that they can make the best choice about what is best for the patient, and for the patient to approach their physician to determine if this could be the compound for them.
SUSAN DENTZER: But many doctors disagree that the marketing is in patients' best interests. Dr. Sharon Levin is a top physician with giant Kaiser Permanente, whose health plans cover eight million people in 11 states and Washington, D.C.
DR. SHARON LEVIN, Kaiser Permanente: What frustrates physicians and what drives them crazy is when the information is misleading, when the images that are presented for the Cox-2 inhibitors imply that these are just better pain relievers, and that in your life you never got the kind of pain relief before that you're going to get with Celebrex or with Vioxx.
SUSAN DENTZER: And in at least one instance, the FDA agreed. It recently told Pharmacia to alter this commercial for Celebrex. In a letter to the company, the agency wrote that the commercial was misleading because the images seemed to overstate Celebrex's effectiveness.
COMMERCIAL: Powerful 24-hour relief.
SUSAN DENTZER: Exposure to this type of direct-to-consumer advertising is increasingly widespread. A new poll by the NewsHour, the Henry J. Kaiser Family Foundation, and the Harvard School of Public Health shows that almost nine out of 10 Americans have seen or heard a prescription drug advertisement on television or radio in the past year. And nearly four out of ten Americans talked with their doctors about an advertised medicine. Dr. Levin says Kaiser Permanente officials knew what the Cox-2 drugs and marketing pressures could mean for the health plans' bottom line. Kaiser Permanente is not affiliated with the Henry J. Kaiser Family Foundation.
DR. SHARON LEVIN: Like every other health care organization, we're faced with mid-double-digit increases in our drug costs on an annual basis. But what it requires of us is to be incredibly judicious and responsible in our use of these medications.
SUSAN DENTZER: So, well before the launch of Celebrex and Vioxx, Kaiser Permanente took steps to try to control their use.
DR. DAVID CAMPEN: Let's take a look at the arthritis here.
SUSAN DENTZER: Kaiser physician David Campen teamed up with researchers at Stanford University to develop a new tool. It was a rating system to help arthritis patients assess their risk for complications and then work with their doctors to choose the most cost-effective drug. Patients at low risk would be advised to take drugs like ibuprofen for their pain -- either over-the-counter medication that could cost as little as 50 cents a day, or a prescription NSAID that could cost about a dollar a day. Patients at high-risk would be steered to Celebrex or Vioxx, at a cost of about $3 to $6 per day. In educational sessions like this one, Dr. Campen and his colleagues discussed how they'd treat various patients.
DOCTOR: Immediately, if you were at high risk, what options would you have for NSAID prescriptions? So what do you do? Which one do you choose?
DOCTOR: I would initially start out on Celebrex or Vioxx.
SUSAN DENTZER: Through techniques such as these, says Levin, Kaiser Permanente has been able to control its outlays for Cox-2 drugs.
DR. SHARON LEVIN: We're probably using less than a third of the Cox-2 class compared to the numbers I've seen for the overall market.
SUSAN DENTZER: Yet, there are signs that market could now expand even further, creating new pressures for health plans and others who pay health care bills. Medical journals recently published the results of new studies sponsored by MERCK and Pharmacia. The companies say these studies prove the drugs are safer for patients than conventional NSAIDS. They've asked the FDA for a label change that would allow them to make the claim. If the FDA finally lets the companies market the Cox-2's as safer, the payoff could be substantial. Hemant Shah, a securities analyst who follows pharmaceutical companies, says the resulting sales growth could be huge.
HEMANT SHAH, Securities Analyst: Several billion dollars worth of commercial opportunity, enormous upside potential, because then it would be very difficult for physicians to resist prescribing Cox-2 even though they may feel that it may not be necessary for most of their patients, or be very difficult for a managed care organization to restrict because now the FDA has come out, in fact, and said that these are better drugs.
SUSAN DENTZER: And that may be the central lesson of the Celebrex and Vioxx case study. A new genie is out of the bottle-- the marketing of blockbuster prescription drugs-- and the economics of health care will never be the same.