GAITHERSBURG, Md. -- Not much in life is black or white, especially when it comes to the risk versus benefit scenarios for disease treatments. But a Food and Drug Administration advisory panel committee that met last month to discuss cox-2 inhibitor safety concerns used little gray in meting out its recommendations.
As a class of drugs, all cox-2 inhibitors carry a risk of heart disease, the committee members decided unanimously. Consequently, all cox-2 inhibitors should carry a black-box warning, most members voted, albeit specific to each drug. And none of the cox-2 inhibitors should be directly advertised to the consumer, the majority of members argued.
The FDA had promised a fast decision on the future of cox-2s following the recommendations.
Only one of the 32 panelists felt that Pfizer's Celebrex should be pulled from the market, making the market-leading arthritic pain reliever the clear choice for doctors prescribing a cox-2 inhibitor, especially because neither Pfizer's Bextra nor Merck's Vioxx fared as well in the voting--the panel was split on the sale of both of those drugs.
"If there is a cox-2 risk, it is lowest with Celebrex versus Vioxx or Bextra, asserted panelist Dr. Steven Abramson, professor and chairman of the division of rheumatology at the New York University School of Medicine.
Another panelist added that while use of Celebrex may represent an increased risk compared with placebo, that risk may be mitigated by the contraindications associated with alternative therapies, such as nonsteroidal anti-inflammatory drugs. "As we consider pulling cox-2s, are we shifting the business to less-safe alternatives?" asked one panel member. Another noted, "We've seen no data over the past two days that would warrant the huge migration of patients from [cox-2s] to NSAIDs."
The introduction of either of Merck's Arcoxia or Novartis' Prexige, the two cox-2s currently in the development pipeline, potentially will be delayed in favor of tests specifically designed to detect any heart disease contraindications.
In the short term, there still will be an erosion of the cox-2 market in favor of other prescription alternatives, such as a prescription proton-pump inhibitor/NSAID combination or even over-the-counter pain relievers. Already, Louisiana's health department has placed restrictions, effective March 15, on the dispensing of cox-2 inhibitors for its Medicaid population, requiring doctors to explain why a patient needs the medicine before pharmacists can fill the prescription. And several panelists, including chairman Alastair Wood, assistant vice chancellor at the Vanderbilt University Medical Center, recommended that patients first try a naproxen product to treat their arthritis pain, such as Bayer's Aleve.
Eventually, however, the established link between cardiovascular disease risks and the prolonged use of cox-2 inhibitors will fade into the background of public conversation. And when that happens, sales of cox-2 inhibitor prescriptions will rise again as doctors weigh the risks of cox-2 inhibitors against alternative treatment options with their patients.
Doctors can expect to have those conversations on appropriate arthritis treatments often in a patient population rife with heart disease. Out of 35.9 million seniors, 21.1 million have arthritis, and 27.9 million have heart disease--according to the National Center for Chronic Disease Prevention and Health Promotion and the American Heart Association, respectively--suggesting there is overlap between the two patient populations.
The cox-2 inhibitor market as a whole may never recapture the $5.3 billion in sales the category had reached by the end of 2004, but the class certainly will be composed of blockbuster drugs.
The market for hormone replacement therapies faced a similar dilemma in 2002, when a clinical trial found a slightly elevated risk of breast cancer in women on an HRT regimen. Sales of all estrogen/progestin combination drugs fell 46 percent in the full year following the news of the increased cancer risk, according to IMS Health figures. But sales were down only 8 perent in 2004, thanks in large part to the introduction of a low-dose Prempro by Wyeth.
Before the meeting, analysts speculated that long-term annual sales of Celebrex would not fall below $1.5 billion, a 44 percent drop from current sales, and that was before advisory panel members voiced their strong support for the cox-2 inhibitor.
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