But for Scolnick and Merck, the event was bittersweet. Just one week earlier, Merck had withdrawn Vioxx, a blockbuster COX-2 inhibitor for arthritis that received FDA approval in May 1999, in the wake of new data that the drug promotes heart attacks. "It's a sad time," Scolnick told reporters, "mostly for patients, many of whom had their lives transformed by Vioxx."

Tragically, many families believe their lives were fatally transformed by Vioxx — and could hold Merck liable for up to $18 billion, according to Merrill Lynch. The Vioxx withdrawal came after five years, $9 billion in cumulative sales, 20 million prescriptions, and possibly 27,000 heart attacks and deaths. Merck's decision came after the APPROVe trial of some 2,600 colon cancer patients revealed almost twice the incidence of serious heart attack — 3.5 percent of patients on Vioxx, compared to 1.9 percent in controls.

In a scathing November New England Journal of Medicine commentary, Eric Topol, Cleveland Clinic cardiologist and one of the first physicians to question the safety of Vioxx in 2001, called for a full congressional investigation into the Vioxx "catastrophe." Topol wrote: "The senior executives at Merck and the leadership at the FDA share responsibility for not having taken appropriate action and not recognizing that they are accountable for the public health ... Had the company not valued sales over safety, a suitable trial could have been initiated rapidly at a fraction of the cost of Merck's direct-to-consumer advertising campaign ($100 million)." Topol later told "60 Minutes" that he had tried to alert Merck chairman and CEO Raymond Gilmartin and research chief Peter Kim, but his calls were never returned.

Worse still, a November front-page story in The Wall Street Journal detailed company e-mail dating back to 1996 that appear to undermine Gilmartin's assertion that the Vioxx problems came "totally out of the blue." In 2000, for example, following analysis of the VIGOR clinical trial data (comparing Vioxx to naproxen), Scolnick wrote in an e-mail to colleagues that cardiovascular risks "are clearly there." Meanwhile, a Merck training document entitled "Dodge Ball Vioxx" presented answers to awkward questions from doctors about the drug's safety.

Merck's steadfast position that it had appropriately considered the safety issues was not helped by a Swiss meta-analysis published in The Lancet last month. A survey of 18 randomized clinical trials involving some 25,000 patients indicated that a significantly increased cardiovascular risk in Vioxx patients was evident as early as 2000, suggesting that Vioxx "should have been withdrawn several years earlier." The Lancet's editor-in-chief, Richard Horton, admonished the "astonishing failures in Merck's internal systems of post-marketing surveillance, as well as ... lethal weaknesses in the [FDA]'s regulatory oversight." He also accused Merck and the FDA of acting out of "ruthless, short-sighted, and irresponsible self-interest."


Blockbuster Disaster 
Among the assorted casualties of the Vioxx debacle are Merck's valuation and reputation as a good corporate citizen, highlighted by its assistance programs for low-income patients and a commitment to treating AIDS in Africa. But this is not about any one company. Indeed, Vioxx is but the latest in a string of would-be blockbuster drugs pulled because of unacceptable side effects. One recommendation is the urgent deployment of pharmacovigilance software. As senior editor Mark Uehling reported last month in his timely feature, "Safety Last?" (Nov. 2004 Bio·IT World, page 30), new solutions could help flag potential safety problems much earlier in the approval process.

Above all, however, it is about patients — patients who are increasingly deluged by slick television commercials touting the latest wonder pill amidst warnings about the dangers of importing unsafe drugs to circumvent exorbitant drug prices. Pharma and the FDA simply must do better to reassure and demonstrate to the public that drug safety comes before sales. 



ILLUSTRATION BY MARK GABRENYA