FDA panel turns down Merck pill

Merck & Co. Inc. failed yesterday to win experts' backing for selling its Vioxx successor drug Arcoxia, reflecting a hardened attitude toward drug safety and pharmaceutical marketing.

The nearly unanimous thumbs-down vote by the U.S. Food and Drug Administration's arthritis advisory committee is not binding. But its recommendation against a drug already approved by several other countries - and shown to be just as effective and risky as a few others - is expected to carry weight with FDA officials, whose formal decision is expected in about two weeks.

If accepted, the recommendation represents the end of nearly a decade of development work and undisclosed millions of dollars expended by Merck. It would dash the hopes of people craving better pain relief, while vindicating critics who long have questioned the safety of Vioxx-like medications.

"You're talking about a potential public-health disaster" if Arcoxia is approved, David Graham, an FDA epidemiologist who also had sounded early warnings about Vioxx, told the panel. He added that, if people start taking Arcoxia in great numbers, "you'll get a repeat of what we had with rofecoxib [Vioxx]."

Merck was seeking approval to sell Arcoxia in the United States for sufferers of osteoarthritis. It told the panel that many Americans still need an effective pain reliever, and it argued that the drug was just as risky as, and perhaps slightly safer on the stomach than, a current widely used drug, diclofenac, sold as Voltaren.

Merck also told the panel that it would strictly warn users about Arcoxia's cardiovascular risks, limit its marketing, and not advertise it on TV or in magazines.

"We are disappointed," Peter Kim, president of Merck Research Laboratories, based in West Point, said in a statement. "We continue to believe that Arcoxia has the potential to become a valuable treatment option for many Americans suffering from osteoarthritis. We are committed to continuing to work with the FDA to discuss the application."

Arcoxia is in a class of drugs called cox-2 inhibitors, once among the most popular and profitable drugs of all time, developed mainly to avoid ulcers or gastrointestinal problems caused by older products.

But all the drugs were labeled potentially lethal after Vioxx, which generated nearly $2 billion for Merck in 2003, was recalled in September 2004 due to studies confirming that it carried cardiovascular risks. The recall socked Merck's morale and market value, and ushered in a new era of safety scrutiny of many medications.

Only one cox-2 inhibitor, Celebrex, made by Pfizer Inc., is still on the market. Another cox-2 drug, Bextra, made by Pfizer, was withdrawn in 2005 at the FDA's request. Novartis AG is working on another cox-2 drug, Prexige, which has not yet faced FDA review.

Merck created Arcoxia in 1997 - long before the Vioxx recall - to be a successor to Vioxx. Merck gained marketing approval in 63 other countries, and reported Arcoxia revenue of $265 million in 2006. But its U.S. application has gone through fits and starts, culminating in yesterday's review.

After a sometimes tense daylong meeting in Gaithersburg, Md., the advisory panel voted 20-1 against recommending approval. It said Arcoxia's risk of causing heart attacks and strokes appeared to outweigh its marginal advantage of relieving pain with fewer minor stomach problems - and likely at a much high price than existing drugs.

Panel members did agree that Arcoxia might benefit some patients. But they noted that Merck gave them no estimates of the number of patients or scope of this so-called unmet need.

Several panel members and speakers also questioned Merck's choice of diclofenac as a comparison drug in safety studies, because diclofenac itself has proved to carry high risks and is not widely used in the United States.

"It is time to shut the door to further additions to this class of drugs," said Sidney Wolfe, medical director of the consumer group Public Citizen. "The idea that there may be some patients, somewhere, who might benefit from this drug is just not sufficient."

Graham, who has clashed with his own bosses at the FDA in the past, said Arcoxia may have the same effectiveness as naproxen - sold as Aleve - but could carry a 2.7-fold increase in cardiovascular risk.

Several panel members also expressed doubt that Arcoxia, if approved with restricted distribution, could be limited to a select group of patients. They noted the industry's record of aggressive marketing and the tendency of patients and physicians to reach for drugs to treat any health problem.

"No matter what we say, you will see it pushed to riskier people, to people who are obese, to people with risk factors," said Christy Sandborg, chief of pediatric rheumatology at Stanford University School of Medicine. "I'm concerned that the safety profile will decay over time. And over time, people who you don't want exposed to this drug will be exposed to it."

Speaking after the vote, Scott Korn, Merck's executive director for global regulatory affairs, based in Upper Gwynedd, said the panel appeared to be concerned more about improper use or over-prescribing than about Arcoxia's inherent safety or effectiveness.

"There was anxiety about how it would be used," Korn said.

Asked whether such concerns were, in fact, a reaction to the industry's own sales and marketing practices, Korn said: "I cannot comment on marketing."

Many Wall Street analysts had expressed doubt that the FDA would approve Arcoxia, and have not factored new Arcoxia revenue into their projections for Merck. The panel vote came just minutes after stock markets closed yesterday. Merck shares closed up 71 cents, or about 1.5 percent, at $46.36.

Merck is based in Whitehouse Station, N.J., and has large operations in suburban Philadelphia.