arthritis drug) ( U.S. News & World Report (Dec 14, 1998):62 (1pages).COPYRIGHT 1998 U.S. News and World Report Inc. It was a
vote with resonance from Wall Street to the homes of America's 23 million arthritis sufferers. Last week, in a stuffy hotel ballroom in Silver Spring, Md., the Food and Drug Administration's
arthritis advisory committee's nine members unanimously recommended approval of Celebrex, G. D. Searle & Co.'s new arthritis drug. Those in the standing-room-only crowd of more than 300
industry scientists and market analysts stood up to watch the show of hands, and many reached for their cell phones the minute the vote was tallied to capitalize on the news. This is a nearly $2
billion-a-year market they're talking about.
But one arthritis-care expert remains skeptical. As a rheumatologist and spokesman for the Arthritis Foundation, Doyt Conn is as eager as anyone to
see arthritis sufferers spring from their rocking chairs. But he says "time will tell" whether celecoxib, a new class of drug, to which Celebrex belongs, that targets arthritis
inflammation and pain with fewer side effects, is worth the hoopla.
Conn's concern is that the drug, while it has been tested in more than 14,000 people (about 10 times more than typically
submitted to the Food and Drug Administration, though no single patient has taken it for longer than about a year), may present unexpected side effects when used by millions for many years.
"There's no reason to expect them to be any better than what we've already got. But there's good reason to hope they're safer," Conn said.
Bad enzyme Doctors have long known that
nonsteroidal anti-inflammatory drugs, or NSAIDs, can relieve arthritis pain by blocking production of cyclooxygenase, or COX for short, an enzyme that helps make prostaglandins, the substance
largely responsible for the pain and inflammation of arthritis. Philip Needleman, then chair of the pharmacology department at Washington University in St. Louis, was instrumental in figuring out
in the 1980s that two enzymes help make prostaglandins, dubbed COX-1 and COX-2, and that COX-2 was the driver of the disease's symptoms. Needleman moved to Monsanto Corp., parent company of
Searle, and, with an army of chemists, began working on a theory of "good enzyme, bad enzyme," to develop a drug that targets only COX-2. It doesn't affect COX-1, which protects the
digestive system from its own erosive acids. Therein lies the benefit of COX-2 inhibitors: They ease pain just like common NSAIDs, including aspirin and ibuprofen, but without interfering with
COX-1, thus reducing the risks of serious side effects like bleeding ulcers. About 107,000 people are hospitalized each year for upper gastrointestinal complications resulting from NSAID use;
16,500 of them die.
The theory that COX-2 inhibitors don't interfere with COX-1's stomach-protecting ability has proved largely true. But competitors of Searle, including Robert Palmer, group
director of rheumatology clinical research and development for SmithKline Beecham, are eager to articulate the complications. Palmer points to a growing body of research that suggests that COX-1
and COX-2 may have overlapping functions and that neither is purely "good" or "bad." The FDA advisory committee urged that the drug's label warn of potential harm to the
stomach and intestines, even though the risk is likely to be smaller than that of available arthritis drugs.
Celebrex awaits final FDA approval, likely by year-end. (Merck & Co. is close
behind with Vioxx, a similar drug.) Celebrex will treat both osteoarthritis, which affects some 21 million people and results from wear and tear on the joints, and rheumatoid arthritis, an
autoimmune disorder that affects about 2 million people.
Needleman, now co-president of Searle and chief scientist at Monsanto, is a rare scientist who has seen an idea through, from tissue in
a petri dish to the imminent prospect of a new drug on the pharmacy shelf. "In science, a hypothesis is something you usually throw away," he said. "This one didn't melt."
Stomach-friendly pain reliever Typical nonsteroidal anti-inflammatory drugs (NSAIDs) reduce pain but they also may upset the stomach. A new NSAID called a COX-2 inhibitor works on the pain
without bothering the stomach.
NSAIDs upset the stomach because they suppress enzymes that produce chemicals called prostaglandins, which protect the stomach from its own acids.
COX-2
inhibitors move directly to the source of pain to suppress the enzymes that produce other prostaglandins that cause pain and swelling
