Merck Recall of Arthritis Medication Vioxx Prompts New Questions on FDA Effectiveness
Merck's voluntary recall of its arthritis drug Vioxx on Thursday "lends new urgency" to congressional inquiries into how effectively FDA responds to drug safety concerns, the Wall Street Journal reports (Wilde Mathews, Wall Street Journal, 10/4).
The company announced the largest voluntary drug recall in history after a study confirmed that Vioxx raises the risk of heart attack and stroke. About two million people worldwide currently use Vioxx, and more than 100 million Vioxx prescriptions have been written since it was introduced in 1999. In 2003, Vioxx had global sales of $2.5 billion (California Healthline, 10/1).
The Senate Finance Committee and the House Energy and Commerce Committee requested a Government Accountability Office study on FDA's safety response after both panels investigated the agency's refusal to allow one of its employees to present his conclusion that antidepressants could be linked to suicidality among children. Following the recall, Senate Finance Committee Chair Chuck Grassley (R-Iowa) said in a statement that he was concerned FDA might have been "foot dragging" in acting on safety concerns related to Vioxx.
Among the studies showing potential risks related to the drug, one was led by an FDA researcher, according to the Journal (Wall Street Journal, 10/4).
Other FDA critics say the recall is "only the latest example" of the agency's "lack of aggressiveness, ... inadequate resources and insufficient legal clout to oversee medicines after they have reached pharmacy shelves," the Newark Star-Ledger reports.
"FDA dropped the ball on Vioxx," Wayne Ray, a Vanderbilt Medical School professor who published a study two years ago linking Vioxx to increased risk of heart disease, said. He added, "FDA has had a pattern of not being able to act quickly when products are already on the market."
However, Steven Nissen, a cardiologist at the Cleveland Clinic who warned of Vioxx-related heart risks in a study published in 2002, said, "FDA did the best it could," adding, "We have a system of adverse event surveillance that is weak. ... There is a limited amount the FDA can do under the current law." Nissen said, "Everything is protected information, and that is why people are calling for more public data on clinical trials. We don't know whether the FDA was unduly influenced by pharmaceutical lobbyists or given all the information it needed."
Sheldon Krimsky, professor of science policy at Tufts University, said, adding that the recall raises serious questions about what "FDA knew and when they knew it" (Cohen/Silverman, Newark Star-Ledger, 10/3).
FDA spokesperson Crystal Rice said agency officials "believe that our actions regarding Vioxx were appropriate and consistent with our public health mission." She added, "No drug is fully safe. Our job is to appropriately balance our decisions, based on the risk-benefit profile for a drug and the societal need and desire for new drugs" (Henderson, AP/Arkansas Democrat-Gazette, 10/3).
Steven Galson, acting director of FDA's Center for Drug Evaluation and Research, said, "We are stuck in the middle of a very contentious and fractious debate that has on one side people saying 'we want more cures, shorter development times' ... and we have people on the other side saying we're too lax."
Galson said FDA is working to improve how it detects and responds to risks from medical products. The agency is focusing on improving data-mining of adverse events by using electronic filing to process reports, examining health care provider data, improving the design of clinical trials and promoting research on pharmacogenetics to help identify people who might react adversely to drugs (Wall Street Journal, 10/4). In addition, FDA might require companies to perform definitive clinical studies that specifically address safety issues even after a drug has reached the market, according to the Washington Post.
Galson said, "We will want more data on [the safety of] long-term use for both drugs in the pipeline and those already approved" (Brown, Washington Post, 10/3). FDA is also considering whether longer studies should be required for Cox-2 inhibitors, the class of drugs to which Vioxx belongs (Pollack, New York Times, 10/4).
Merck on Friday said it will create a reserve to cover potential legal costs related to lawsuits filed by Vioxx users who say the drug caused heart problems, the Philadelphia Inquirer reports. Merck officials said they do not know how many Vioxx users have taken the drug regularly for 18 months -- the amount of time that elapsed before heart-related risks appeared in the clinical trial that prompted the recall (Goldstein, Philadelphia Inquirer, 10/2).
So far, patients who said they have been harmed by Vioxx have filed about 200 lawsuits. Several of those cases have been consolidated into two trials in Los Angeles and New Jersey (California Healthline, 10/1). On Friday, two New York residents who had heart attacks while taking Vioxx filed lawsuits against Merck in New York State Supreme Court, alleging Merck was aware of the drug's heart risks as early as 2000 and failed to notify consumers (Lam, Long Island Newsday, 10/2).
In 2001 -- two years after the drug's market release -- a report in the Journal of the American Medical Association found signs that the drug might increase the risk of cardiovascular disease. Merck added the study's finding to Vioxx's label in April 2002 at FDA's request (California Healthline, 10/1).
In addition, a Missouri resident has filed a lawsuit against the drug maker, alleging Vioxx was responsible for the death of her daughter, who took Vioxx for more than two years before dying of a heart attack in 2002 at age 34. The lawsuit was filed as a class-action case with only one named plaintiff. In addition to compensatory and punitive damages, the lawsuit seeks funds for medical monitoring of Vioxx users (AP/South Florida Sun-Sentinel, 10/3).
Legal analysts anticipate "a flood of cases" will be filed, and they expect the recall "could add momentum to those already filed," the Bergen Record reports. According to Anthony Sabino, associate professor of law at St. John's University's Tobin College of Business, "It's going to take years to sort out Vioxx," and within days, Merck likely will establish a reserve fund that could reach billions of dollars to prepare for potential damages (Krauskopf, Bergen Record, 10/3).
Some attorneys estimate Merck's litigation costs could be similar to the more than $1 billion in legal costs incurred by Bayer AG over its cholesterol-lowering drug Baycol. Merck spokesperson Tony Plohoros declined to say how large a reserve the company would create, adding, "It is not possible at this time to reasonably estimate the company's potential liability." The first Vioxx-related lawsuits could go to trial as early as the end of this year (Philadelphia Inquirer, 10/2).
Pfizer officials on Friday announced that routine monitoring of three long-term studies of Celebrex, a Cox-2 painkiller and Vioxx rival, have found the drug shows no signs of cardiac safety risk (Hensley, Wall Street Journal, 10/4). The three trials involve more than 6,000 patients, and Pfizer officials said "none of the safety problems Merck found with Vioxx" has been detected in patients taking Celebrex, the Star-Ledger reports (Schwab/Todd, Newark Star-Ledger, 10/2).
Joe Feczko, Pfizer's president for drug development, said company officials are "even more confident" of the drug's safety because studies have consistently shown no added cardiovascular risks. He added, "We have not been asked to stop or change any aspect of the studies related to cardiovascular risk" (Wall Street Journal, 10/4).
However, labels on Celebrex, as well as another Cox-2 drug, Bextra, list cardiovascular side effects as "possible, though uncommon," Long Island Newsday reports (Rabin, Long Island Newsday, 10/2).
The following opinion pieces address the Vioxx withdrawal:
- Eric Topol, New York Times: The impact of Vioxx's withdrawal is "far-reaching," as it highlights the "absence of [FDA] oversight of the pharmaceutical industry" and the possible dangers of all Cox-2 inhibitors, Topol, chair of the Cleveland Clinic's department of cardiovascular medicine, writes in a Times opinion piece. Topol cites, among other trials, a 2001 study he worked on that found Vioxx had a heart attack risk that was five times greater than the over-the counter drug naproxen, and he states that Merck "finally had to acknowledge the truth [about Vioxx], but only by accident." However, Topol notes that the Merck study, which found that 3.5% of patients taking Vioxx experienced heart problems, might have "greatly underestimated" the risk of the drug and other Cox-2 inhibitors. Topol states that the study "avoided" patients with heart disease, "who frequently have arthritis as well and are thus prime users of anti-inflammatory medicines." Topol writes that FDA could have "forced Merck to do the appropriate research studies, but instead it was a bystander." Topol concludes that the nation needs a "stronger regulatory agency" that would limit manufacturers' direct-to-consumer advertising and "compel pharmaceutical companies to do the proper studies" (Topol, New York Times, 10/2).
- Terry Keenan, New York Post: The "one-day meltdown" of Merck's stock -- "once considered the safest of the blue chips" -- shows Wall Street is "flashing a warning that there are broader implications [of the recall] that could extend well into the future," Keenan, senior business correspondent and anchor on Fox News Channel's "Cashin' In," writes in a Post opinion piece. Keenan writes that on "Vioxx Thursday," investors "wiped away within minutes" $27 billion in market value. "Never before has an announcement cost more investors more money more quickly," Keenan writes, adding that the "Merck mess" is "not good news, and Wall Street is warning as much." Keenan says the company now faces an "avalanche of lawsuits as far as the eye can see," adding that "the tort bar has just found its next big, rich target, and the stock market is starting to discount the fallout." Keenan also notes that the withdrawal of Vioxx could "cast a pall over the entire drug sector" by causing FDA to "do the right thing and start to become more cautious in the way it approves drugs" (Keenan, New York Post, 10/3).
APM's "Marketplace" on Friday included an interview with Rich Thomaselli, health marketing reporter for Advertising Age, about how Vioxx's recall has "rekindled concerns" about direct-to-consumer prescription drug advertisements (Brown, "Marketplace," APM, 10/1). The complete segment is available online in RealPlayer.
In addition, CNN's "Saturday Morning" included an interview with Dr. David Pisetsky, chief of rheumatology at Duke University Medical Center, about the recall (Nguyen, "Saturday Morning News," CNN, 10/2). The complete transcript is available online.