Painkiller in the dock

from Nature

Still reeling from the loss of its blockbuster pill Vioxx, Merck is now in court to face its first lawsuit over the drug. Meredith Wadman reports.

The attention of the global pharmaceutical industry is fixated this month on a courtroom in Texas. In the little town of Angleton, Merck is defending an allegation that its blockbuster painkiller Vioxx killed Robert Ernst, a 59-year-old personal trainer from nearby Keene.

The case is the first of some 4,000 Vioxx lawsuits filed against Merck to come to trial. The company, based in New Jersey, withdrew the painkiller from the market last September, after one of its clinical trials showed that prolonged use of the drug doubled the risk of heart attacks and strokes.

Ernst died of an arrhythmia in May 2001 after using Vioxx for eight months. Arrhythmias, or irregular heartbeats, range from relatively benign conditions that can be treated by medication to sudden, fatal disturbances of the kind that killed Ernst.

For Merck, “a lot depends on this first case”, says Tony Butler, an analyst at Lehman Brothers in New York, who watches the company closely. If the plaintiffs win and secure a big monetary award, it could encourage a huge number of additional lawsuits. A victory for Merck could significantly reduce its financial liability over Vioxx, which analysts have estimated at anywhere between $4 billion and $20 billion. It is fear of this liability — even more than the lost annual revenue of some $2.5 billion — that caused Merck's shares to plunge so sharply when it recalled the drug (see Graph).

Under attack

Lawyers acting for Ernst's widow Carol allege that Merck, which had marketed Vioxx since 1999, knew early on about its dangerous cardiovascular effects and stifled that information in its quest for profit.

Their argument was bolstered early in the trial, on 19 July, when lead attorney Mark Lanier presented as evidence a letter that Merck sent to thousands of doctors during 2001. This said that, in the largest clinical trial of Vioxx, only 0.5% of about 4,000 subjects taking the drug had experienced “cardiovascular events” including heart attacks and strokes. In fact, that rate, as Merck reported it to federal regulators, was 14.6%. Ernst's doctor received the letter in April, 2001, the month before Ernst died.

“You-all didn't tell the doctor the truth about the safety of Vioxx, did you?” Lanier asked Nancy Santanello, Merck's top epidemiologist, who is the company's key witness. “Perhaps it's not very precise,” she conceded after prolonged questioning.

But Jonathan Skidmore, a defence attorney with the Washington firm of Fulbright & Jaworski, accused Lanier of clouding the central issue: whether Ernst's death from an arrhythmia was caused by Vioxx. “This is a case about causation and science,” said Skidmore. “A sudden death is a tragedy in any family, but the evidence here will show that Vioxx did not cause Mr Ernst's death. There is no credible scientific evidence associating Vioxx with an increased risk of arrhythmia.”

Merck's lawyers will also focus on timing. Ernst took Vioxx for eight months, but in the study that led to the drug's recall, the increased risk of heart attacks and strokes did not appear until patients had been taking the drug for 18 months.

Merck has contended from the outset that it followed Food and Drug Administration (FDA) safety regulations religiously as it developed Vioxx. “Merck acted responsibly,” says Kenneth Frazier, the company's general counsel.

The trial, which began on 14 July, has been packed out by dozens of reporters, investors and lawyers involved in other pending Vioxx lawsuits. It is pitting the folksy but formidable Lanier against some of America's most seasoned corporate lawyers, from two powerhouse Washington law firms.

Their respective styles have contrasted vividly during the trial, which is expected to run until late August. Lanier calls the jurors by their first names and projects slides with pithy slogans, such as “Merck-y ethics”, as he seeks to build a case that the company knowingly deceived some 20 million patients who took Vioxx. David Kiernan, the surgeon and lawyer who gave Merck's opening arguments on 14 July, read from notes and quoted long excerpts from FDA letters.

Biological actions

But whichever rhetorical method they use, the winner of this case will need to convince the jurors of one central fact: that Vioxx either did or did not contribute to Robert Ernst's death. That may come down to a detailed pathophysiological discussion of how arrhythmias can be provoked by heart attacks, and whether, despite Merck's public statements to the contrary, Vioxx can sometimes cause arrhythmias.

For Merck, which employs more than 62,000 people, including 8,000 researchers, across 150 countries, the stakes could hardly be higher. Wyeth, another drug firm based in New Jersey, has so far paid $21 billion in charges related to lawsuits filed by people who took its diet drug fenfluramine. The drug was pulled from the market in 1997 after being linked to heart-valve damage.

But a prominent Dallas lawyer, Kip Petroff, failed to win substantial settlements for fenfluramine plaintiffs until he took Wyeth to trial a few times in small courtrooms much like the one in Angleton. After that, recalls Joseph Goulden, a Washington writer who will deal with such cases in a forthcoming book, “settlements rained down like hail on a tin roof in an east Texas thunderstorm”.