On the day it won a court case in Texas over Vioxx, Merck & Co has been hit by the publication of a meta-analysis which claims that a cardiovascular risk associated with the drug was known well before the painkiller was withdrawn.

Research published in the Archives of Internal Medicine looked at 30 studies on 20,152 patients looking at Vioxx (rofecoxib) before it was withdrawn in September 2004 on the basis of the APPROVe study. According to the authors of the pooled data, as of December 2000, 21 of these trials had been completed and the risk of a cardiovascular thromboembolic (CVT) adverse event or death was greater among subjects assigned to the Vioxx group.

Subsequently collected data through June 2001 showed that rofecoxib was associated with a 35% increased risk of a CVT adverse event or death and by April 2002 that had risen to 39%. By September 2004, it was up to 43%, compared with placebo.

The researchers say the data used in the study “were not publicly available for analysis by independent investigators” at the time Vioxx was being marketed “and have only now become available through litigation”. They argue that “physicians and the public deserve to be in a position to make informed choices about risks and benefits, and the disclosure and dissemination of information about potential risk immediately after its recognition is absolutely essential”.

The authors add that the study suggests that “such analyses should be ongoing for all drugs for which trials are being conducted, with attention to the rapid addition of new data about potential harm to any cumulative pooled analyses”.

Merck has responded quickly, saying that the study “used unreliable methods and reached incorrect conclusions”. The company insists that the first time it observed a difference in a placebo-controlled study was when it learned the results of the APPROVe study and “we voluntarily withdrew Vioxx from the market within a week of those results”.

The New Jersey-based drugs major goes on to list what it perceives are the flaws in the AIM analysis. For example, Merck says “we do not believe deaths from all causes – including, in the case of Vioxx, electrocutions, infections and trauma – are the most reliable way to examine a question about cardiovascular safety”. The analysis also included events that occurred after a patient had stopped taking any study drug.

The company concluded that it acted responsibly, from researching Vioxx prior to approval in studies with some 10,000 patients to monitoring the medicine while it was on the market and withdrawing it. “Our decisions were based on the data from well-controlled clinical trials,” Merck concluded.

No Medicaid refunds for Texas
Better news for Merck came with the news that a judge has dismissed all claims in a Vioxx lawsuit filed by the State of Texas. The latter was seeking damages and penalties for alleged violations of the Texas Medicaid Fraud Prevention Act, including a refund for money spent on Vioxx.

Merck said the evidence showed that the company “acted responsibly and truthfully in its communications about Vioxx with the State of Texas, doctors in the state and the US Food and Drug Administration”. The company noted that the case is the first of 12 filed by state attorneys general over the drug, with a trial in Louisiana scheduled to begin on April 12 next year.

In November 2007, Merck reached a $4.85 billion settlement to resolve state and federal myocardial infarction and ischemic stroke personal injury claims. More than 99% of all eligible personal injury claimants enrolled in the programme, which is “proceeding as scheduled,” the firm added.

Merck wins Fosamax case
On a busy day for Merck, another judge, this time in Manhattan, dismissed claims that the company’s osteoporosis drug Fosamax (alendronate) caused a plaintiff’s osteonecrosis of the jaw.

US District Court Judge John Keenan, who declared a mistrial in the first Fosamax case to reach the courts in September, said that Bessie Flemings, who is in her mid-70s, “has offered no other evidence to establish” that the drug caused her to develop ONJ, “and therefore her failure-to-warn claim is insufficient as a matter of law”.