Merck Mess Shows FDA's FlawsJan 4, 2005 | www.thestreet.com
When activists were battling to accelerate the approval of AIDS drugs in the late 1980s, they surely never dreamed that a souped-up pain pill like Vioxx would ride on their coattails.
The crusaders made history. They stormed the headquarters of the Food and Drug Administration in the fall of 1988, making a powerful statement for dying AIDS patients. Just eight days later, the agency adopted regulations aimed at trimming a thicket of red tape. It quickly began blessing new AIDS treatments in the years that followed.
"Without this [process] , we would not have the cocktail" famous for treating AIDS and saving countless lives, says Michael Weinstein, president of the AIDS Healthcare Foundation.
But despite the early success, fast-track approval has started looking like a double-edged sword for the pharmaceutical industry as well as for consumers. While some treatments clearly merit special handling, critics say, the push to bring new products to market has compromised the integrity of the agency's drug-approval apparatus.
"The drug industry drove a Mack truck through the exception created for life-threatening illnesses," Weinstein continues. "Basically, everything became 'fast-track.' "
Questions about the FDA's approval process, and the agency's oversight of drug safety in general, loom especially large in the wake of Merck's (MRK:NYSE) mishandling of Vioxx.
The New Jersey pharmaceuticals titan stunned the world in late September by suddenly yanking Vioxx, one of its bestselling drugs, after a study showed that it increased the chances of heart attacks. Rival Pfizer (PFE:NYSE) has since warned that its own so-called Cox-2 inhibitor, Celebrex, could pose cardiac risks as well, though the New York-based company continues to sell its drug. Both companies had touted their painkillers as safe in the past.
In this second of five articles, TheStreet.com examines how the government's lax regulatory stance laid the groundwork for a drug disaster that ultimately proved hazardous to consumers and to Merck itself.
Weinstein calls Vioxx a "me-too drug for arthritis pain" that should never have merited a priority FDA review. He claims that Merck "hijacked" the fast-track approval process, which allows drugs to hit the market after just six months of study by the government, and unnecessarily placed the public at risk as a result.
For its part, Merck insists that it carried out multiple studies that exposed no cardiac risks before it submitted Vioxx to the FDA for review. It also says that it sought quick approval for the drug because it offered pain relief without the serious, and sometimes fatal, stomach problems caused by other treatments.
The FDA offered Vioxx its blessing, comparable to the Good Housekeeping Seal of Approval in the eyes of the public, in mid-1999. But the agency did so despite its own concerns and lack of information about cardiac risks that, some experts already feared, could far outweigh any stomach protection offered by the drug.
One lawmaker marveled at the situation during a special November hearing of the U.S. Senate called by Iowa Republican Charles Grassley.
"If I knew that FDA had approved this drug for my use, but there was a couple of paragraphs back at FDA that said, 'It may cause heart attacks possibly, but we don't have enough data, and no more data is needed.' I don't think I would have taken it," said Sen. John Breaux, a Democrat from Louisiana. "It would scare the hell out of me."
Bruce Psaty, an epidemiologist and drug-safety specialist, sees clear problems with the FDA's fast-track process.
Prior to widespread use of that process, he told the Senate, only 2% of newly developed drugs entered the U.S. before first appearing in other markets, typically in Europe. By the late 1990s, he said, some 68% of drugs were launched in the U.S. instead. As a result, he indicated, the U.S. is exposing millions of its citizens to new drugs that could pose safety risks.
"In other words, we don't have a test market?" Sen. Jim Bunning, a Kentucky Republican, asked during the special Senate hearing.
"We are the test market," Psaty replied.
Prior to FDA approval, Psaty explained, Vioxx had been tested at common doses of 12.5 and 25 milligrams on just 371 patients for at least one year. The only large study to explore the drug's cardiac risks had yet to be completed.
Some experts, including an FDA veteran, also worry about the agency's follow-up treatment of the drugs it has blessed already. David Graham, an associate director inside the FDA's Office of Drug Safety, claims that agency reviewers regard the drugs they approve "as one might regard their own child" and, as a result, tend to protect them at the expense of the public.
Graham shook up the Senate audience and drug investors by singling out five medications, besides Vioxx, that could pose serious risks to consumers. He elaborated on the possible dangers of Serevent, an asthma drug manufactured by GlaxoSmithKline (GSK:NYSE) , in particular.
Even before the drug's FDA approval, Graham said, a broad study had shown "with 90% certainty" that Serevent increased the risk of asthma deaths. But, he added, that wasn't quite enough evidence to keep the drug from hitting the U.S. market.
"Under [the FDA's] paradigm, a drug is safe until you can show that with 95% or greater certainty it is not safe," Graham explained. "I don't think that 95% certainty protects Americans. What it does is it protects the drug."
With Vioxx, Graham said, the U.S. now faces "what may be the single greatest drug safety catastrophe in the history of this country."
Moreover, he said, the whole problem should and probably could have been avoided. Instead, he said, the FDA fell down on the job, and up to 139,000 Vioxx users suffered major, sometimes fatal, complications. To drive his point home, he said that two to four airplanes would have to crash every week to hurt as many people as Vioxx did over the past five years.
Graham clearly believes that many of those Vioxx users could have been spared. He faults Merck and his own agency for failing to alert the public after a major study in 2000 exposed cardiac risks linked to the painkiller.
Instead, he says, Merck negotiated with the FDA for nearly two years before finally disclosing the risks as a precaution rather than a regular or especially powerful "black box" warning.
To be fair, the FDA did crack down at least once on Merck's promotion of Vioxx. The agency sent a warning letter to the company about a 2001 press release headlined "Merck Confirms Favorable Cardiovascular Safety Profile of Vioxx." Merck based its announcement on the 2000 study that exposed the painkiller's cardiac risks.
"It's a strong letter," Breaux noted. "They went crazy."
Overall, however, the Senate mostly heard about a warm relationship viewed as too cozy by some between the FDA and the drug industry it is charged with regulating. Graham hinted at broad problems throughout the agency.
"FDA has this amazing conflict-of-interest policy," he explained. "You can come in, get money from Merck, get money from Pfizer, and what FDA will say is, 'Well, since you're getting money from everybody, you don't have a conflict.' They have ways of waiving these conflicts of interest that are meaningful all the time."
Looking ahead, however, Weinstein believes the Vioxx debacle may finally trigger major industry changes. He points to sweeping reforms elsewhere as the basis for his hope.
For example, he says, the government managed to overhaul the tobacco industry. In addition, he says, New York Attorney General Eliot Spitzer has brought much-needed improvements to the investment world.
He now believes the drug sector could be on its way to becoming something other than what he views as an "outlaw industry."
"Here's an industry that makes drugs that save people's lives, and it manages to have a reputation for being selfish, greedy and irresponsible. But the day of reckoning," he proclaimed, "is here."