In November 2007, drug maker Merck & Co. announced it would pay $4.85 billion to resolve claims that its anti-inflammatory medication Vioxx caused heart attacks and strokes (including sudden cardiac death). The Vioxx settlement remains the largest pharmaceutical settlement in history.
Beasley Allen’s Andy Birchfield and his team of lawyers – Benjamin Locklar, P. Leigh O’Dell, and W. Roger Smith III – played an integral role in the development of the Settlement Program and in Merck agreeing to settle these cases.
What is Vioxx
Vioxx is a brand name of a prescription painkiller made by Merck. It contains the active ingredient rofecoxib, which is in a class of drugs called COX-2 selective nonsteroidal anti-inflammatory drugs (NSAID). Vioxx was used to treat osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, acute pain conditions, migraine and menstrual cramps.
Drugs Similar to Vioxx
Other COX-2 selective NSAIDs on the market include:
- Celebrex (celecoxib)
- Bextra (valdecoxib)
Vioxx is also related to nonselective NSAIDs such as
- Advil, Motrin (ibuprofen)
- Aleve, Anaprox, Naprelan, Naprosyn (naproxen)
FDA Approval of Vioxx
Vioxx was originally approved by the Food and Drug Administration (FDA) in May 1999 based on studies of approximately 5,000 patients. Those studies did not indicate an increased risk for cardiovascular events in patients treated with Vioxx.
Vioxx was approved under the FDA’s 6-month priority review, as opposed to the standard 10-month review process most medications are put through. The agency granted Merck a priority review for Vioxx because the painkiller had the potential to provide a significant therapeutic advantage over existing approved NSAIDs because it had fewer gastrointestinal side effects, including bleeding. Drugs under priority review must still meet rigorous standards for safety, efficacy, and quality as all drugs submitted for FDA approval.
Vioxx works by blocking an enzyme linked to pain and swelling. Some studies suggest that this mechanism contributes to blood clotting and hypertension.
Vioxx Side Effects
In June 2000, Merck conducted a study called VIGOR (Vioxx Gastrointestinal Outcomes Research) to study its effects on the gastrointestinal tract. NSAIDs can cause ulcers and other GI problems by interfering with the stomach’s ability to protect itself from gastric acids.
Merck needed a blockbuster drug. They needed a big revenue source.
— Andy Birchfield
The VIGOR study showed that patients taking Vioxx had fewer stomach ulcers and bleeding than patients taking naproxen, another NSAID. But it also revealed that patients taking Vioxx had a five times greater risk of heart problems compared to patients treated with naproxen.
At the time, Merck officials tried to explain the outcome by suggesting naproxen helped protect the heart rather than Vioxx damaging it.
The results of the VIGOR study were discussed at the FDA’s Arthritis Advisory Committee meeting in February 2001. As a result, in April 2002, new safety information about the VIGOR study was added to the Vioxx safety label. Merck also began a longer-term study of the drug to obtain more data on heart attack and stroke risk with chronic use of Vioxx.
Meanwhile, in 2001, Merck launched the APPROVe trial (Adenomatous Polyp Prevention on Vioxx), a three-year study to determine whether the 25mg dosage was effective at preventing the recurrence of colon polyps. The study was stopped early after researchers discovered that patients taking Vioxx continually for 18 months had a two-fold greater risk for serious cardiovascular events compared to patients taking a placebo.
Merck announced Sept. 30, 2004, that it would withdraw Vioxx from the market worldwide based on findings from the APPROVe trial, which showed that after 18 months, patients who took 25 milligrams of Vioxx had an increased risk for cardiac events, including heart attacks and strokes, compared to people taking a placebo.
About 20 million Americans took Vioxx in the five-and-a-half years it was sold. During that time, Vioxx generated roughly $2.5 billion in sales.
Bothered by the serious cardiovascular risks posed by Merck’s VIGOR study, Dr. David Graham, an epidemiologist and Associate Director of the FDA’s Office of Drug Safety, led a study involving 1.4 million people between the ages of 18 and 84 who were treated between January 1999 and December 2001 with one of the new COX-2 drugs or an older NSAID.
In 2005, Dr. Graham published his findings from that study in The Lancet. Based on his review, Dr. Graham estimated that Vioxx raised a person’s risk of coronary heart disease by 34 percent compared to a similar COX-2 drug, Celebrex.
Dr. Graham estimated that during the five years Vioxx was on the market in the United States, it caused between 88,000 and 140,000 additional cases of serious heart disease, and of those cases, about 44 percent – or between 39,000 to 61,000 – resulted in death.
In November 2004, in a segment about Vioxx for 60 Minutes, Ed Bradley reported that based on a review of Merck documents and interviews with outside scientists, Merck had concerns about cardiovascular risks with Vioxx long before it withdrew the drug from the market.
“To say that the APPROVe study was the first indication that [Merck] had of a(n) [increased cardiovascular] risk is absolutely untrue,” Beasley Allen’s Andy Birchfield told Bradley. “You know, they had warning sign after warning sign, study after study, that suggested a significant, a substantial increase in risk.”
But why would Merck continue to sell the drug knowing it could seriously harm or even kill people, Bradley asked Birchfield. “Merck needed a blockbuster drug. They … had drugs that were coming off patent and they needed a … big revenue source,” Birchfield explained.
In March 2000, the day Merck’s research president learned about the results of the VIGOR study – less than a year after Vioxx hit the market – he expressed concerns in an email saying the heart problems “are clearly there … It is a shame.”
Attorneys representing patients suing Merck said that there were internal memos and emails from as early as 1996 indicating researchers knew there was an increased risk of heart problems with Vioxx.
In August 2001, cardiologists Debabrata Mukherjee, Steven Nissen and Eric Topol published a meta-analysis in the Journal of the American Medical Association that delved into VIGOR data from all FDA sources and were able to discount the hypothesis of Merck’s previous assertation that naproxen protected the heart.
Dr. Topol, chief of cardiovascular medicine at the Cleveland Clinic, also examined a clinical trial conducted by Merck in 1998 called Study 090. The data, which was never published, showed that among 978 patients, serious cardiovascular events were found about six times more often in patients treated with Vioxx than those taking a placebo or another painkiller.
Dr. Topol told 60 Minutes that study was too small to be statistically significant, but combined with the VIGOR study, it showed that by 2000, there was solid evidence that Vioxx was dangerous. Dr. Topol said he tried to warn Merck but neither the CEO nor the director of research returned his calls.
Instead, Merck continued its $500 million marketing campaign and instructed its sales representatives to dodge questions about the cardiovascular risks with Vioxx when pitching the drug to doctors.
Merck also held to its stance that the heart attack and stroke risks with Vioxx were only a risk in patients who took the drug continuously for 18 months. But in May 2006, outside analysis of the Vioxx APPROVe study found that the cardiovascular risks from Vioxx began shortly after patients started taking the drug. Many plaintiffs who had filed suit against Merck reported taking the drug for less than 18 months.
In the years that followed, numerous epidemiological studies began turning up more evidence that Vioxx was dangerous.
Shortly after Merck pulled Vioxx off the market, the company was hit with tens of thousands of lawsuits.
- August 2005 – The first Vioxx lawsuit was tried. It involved the case of Robert Ernst, a marathon runner who died in 2001, after suffering a heart attack while taking Vioxx for eight months. Despite Merck assembling a team of 100 lawyers, a Texas jury found in favor of Ernst and awarded $253 million to his widow. The award included $24.5 million for Mrs. Ernst’s mental anguish and economic losses, and an additional $229 million in punitive damages for Merck’s recklessness in selling Vioxx despite knowing it had been associated with heart risks. A judge later reduced the verdict to $26 million.
- August 17, 2006 – A federal jury in New Orleans ordered Merck to pay $51 million to Gerald Barnett, who sued the company after suffering a heart attack in 2001 while taking Vioxx. The award included $$50 million in compensatory damages and $1 million in punitive damages. A federal judge found the reward “grossly excessive,” and in June 2007, Barnett agreed to a reduced $1.6 million verdict.
In 2007, after 11 months of negotiations culminating in around-the-clock bargaining to reach final details, Merck agreed to pay $4.85 billion to end thousands of Vioxx lawsuits from about 48,000 plaintiffs.
In 2011, Merck agreed to pay $950 million to the U.S. Department of Justice to settle criminal charges and civil claims related alleged illegal marketing of Vioxx, as well as an additional $628 million for alleged off-label marketing and for making false statements about the drug’s heart risks.
In January 2016, Merck agreed to pay $850 million to settle a federal class action lawsuit brought by its investors over allegations that the company failed to adequately inform them about the heart risks associated with Vioxx.
- The Lancet
- CNN Money