Though a Food & Drug Administration advisory panel stopped short of pulling popular prescription painkillers from the market this week, the drugs' makers still face big headaches from lost sales and potential lawsuits based on research showing increased risk of heart attacks and strokes for some patients that use the drugs.
An FDA advisory panel on Friday said that the benefits of Celebrex, Pfizer’s top-selling painkiller, and a similar Pfizer drug called Bextra, outweigh the risks for patients who don’t respond well to alternative treatments. The panel spent three days reviewing the class of drugs known as COX 2 inhibitors.
“I think there's clearly a significant increased risk,” said panel member Michael Domanski, head of clinical trials at the National Heart, Lung and Blood Institute. “(But) I don't think it ought to be pulled out of the hands of physicians that prescribe it.”
The panel also narrowly voted — 17 to 15 — to allow sales of Merck’s Vioxx, which the company voluntarily withdrew in September. Merck stopped selling Vioxx, its top-selling drug in the class, after a study showed the drug doubled the risk of heart attack and stroke when taken for at least 18 months.
The move cost the company an estimated $700 million in lost sales in the fourth quarter, a big factor in Merck’s 22 percent drop in fourth quarter earnings. Merck said earlier this week that it might consider putting Vioxx back on the market if the FDA decides its cardiovascular risks are similar to those of related prescription pain relievers. The government's final blessing for Vioxx still has to come from the FDA, but a spokesman said the agency generally follows the advice of the advisory panel.
COX-2 inhibitors selectively block a protein called COX-2 that has been linked to inflammation. When first prescribed in 1999, they quickly became a popular alternative to older painkillers known as non-steroidal anti-inflammatory drugs, or NSAIDS, because they are gentler on the stomach. But some COX-2 pain relievers have been found to have another, potentially fatal, side effect.
“COX-2 in the heart is a heart-protecting enzyme,” Public Citizen’s Dr. Sidney Wolfe told the advisory panel. “If you knock this enzyme out — which is what these drugs do — you’re knocking out the heart’s ability to protect itself.”
Wolfe told the panel he believes all drugs in the class should be banned.
COX-2 pain relievers also drew fire this week from European regulators, who slapped restrictions on their use in the European Union because of the risk of heart damage. The European Medicines Agency said Thursday that doctors should provide the lowest dose and shortest course possible. The regulators also warned that Merck's Arcoxia drug should not be used by some patients with high blood pressure.
Since the withdrawal of Vioxx last year, concerns about harmful side effects of COX-2 inhibitors have hurt sales of the entire class of drugs. U.S. sales of Pfizer’s Celebrex are expected to fall 44 percent this year to $1.3 billion, according to Catherine Arnold at Credit Suisse First Boston. Sales of Pfizer’s other Cox 2 painkiller, Bextra, are expected to fall 56 percent this year to $500 million, she said in a recent research note.
Lost sales are only the beginning of the potential financial impact of the discoveries about harmful side effects of Cox-2 inhibitors. Already, more than 100 Vioxx cases have been filed in state and federal courts. Pfizer faces fewer suits from patients who used Celebrex and Bextra, but that could change if new research finds greater frequency of side effects than originally reported for its COX 2 drugs.
Merck won a legal victory this week by getting many of the federal Vioxx suits consolidated in one venue — heading off the added cost of fighting these cases on many fronts. But some of the suits filed in state courts likely will still proceed individually.
And more plaintiffs could be waiting in the wings. An estimated 20 million patients used Vioxx; tens of thousands of those patients may have suffered cardiovascular problems. If Merck loses some of the early cases to come to trial, other patients could be encouraged to file their own suits. The first two cases are expected to go to trial in May, with another round of cases are scheduled for July.
Merck has said it will vigorously defend against claims that it knew of the harmful effects and continued to sell Vioxx anyway. And the company's case could be helped by evidence that the harmful side effects are common to all COX-2 inhibitors, not just Vioxx. The company has already set aside $675 million to cover the cost of fighting these suits.
But some analysts believe that could be only a down payment on the eventual cost. CSFB’s Arnold believes Merck's liability could top $12 billion, based on the number of patients who took Vioxx and the size of awards paid to patients who suffered harmful side effects from a popular anti-obesity drug fen-phen, sold under the name Redux by Wyeth-Ayerst Laboratories, a unit of American Home Products.
The loss of its leading painkilling drug isn’t Merck only headache. Sales of its biggest seller, the cholesterol drug Zocor, hit $4.6 billion last year but have been falling. Merck’s patent on the drug expires next year.
Last month, an appeals court ruled that Merck’s patent on its second biggest drug, Fosamax, will expire earlier than the company than expected. Unless it can get the ruling reversed, generic drug makers can begin selling the anti-osteoporosis drug beginning in 2008. Fosamax generates about $3.2 billion a year in sales for Merck.
The outlook is mixed for the rest of the $235 billion U.S. prescription drug industry. Sales grew 8.3 percent last year, but that was the slowest rate in nearly a decade, according to a report by IMS Health.
