With all eyes firmly on GlaxoSmithKline’s Avandia (rosiglitazone) all week in the wake of a New England Journal of Medicine data meta-analysis showing a massive increase in the risk of cardiovascular events associated with the diabetes drug, it was the turn yesterday of Merck & Co after a conservative watchdog group issued new reports of serious adverse events linked to its cervical cancer vaccine Gardasil.

Judicial Watch, a US public interest group set up to investigate government corruption, released documents obtained from the Food and Drug Administration under the Freedom of Information Act spotlighting 1,637 reports of adverse reactions to Gardasil since its approval in June last year.

More seriously, three deaths were also associated with the vaccine, according to the FDA documents, after the girls experienced heart problems and/or blood clotting – in one case as little as three hours after being immunized - and there were 371 serious reactions ranging from paralysis and seizures, to spontaneous abortions and foetal abnormalities amongst pregnant women who’d been given the human papillomavirus vaccine.

A “catalogue of horrors”

Reading like a “catalogue of horrors,” Judicial watch President Tom Fitton added: “Any state of local government now beset by Merck’s lobbying campaigns to mandate this HPV vaccine for young girls ought to take a look at these adverse health reports.” However, an article in the Wall Street Journal cites FDA and company spokesman as saying the adverse events were “probably unrelated” to the vaccine. Indeed, it adds that two of the fatalities were in girls also on oral contraceptives, which have been linked to thrombosis and embolism.

This was echoed by a spokesperson from Sanofi Pasteur MSD, the UK licensee for Gardasil, who told PharmaTimes World News that such spontaneous adverse event reports show a temporal rather than causal relationship and added that the data need to be systematically evaluated before the company and the regulators can make an accurate judgement. He also noted that the dataset filed with regulators contained data on 25,000 women, therefore its safety profile has been well documented, with heart problems and/or blood clotting not listed as potential side effects. Finally, the spokesperson did note that Gardasil is contraindicated in pregnancy and that it it likely these women were in the very early stages and therefore were unaware of the pregnancy.

However, a recent NEJM report has also raised doubts about Gardasil’s long-term effectiveness and the value of across-the-board vaccination for young women. In an editorial in the NEJM, Drs George Sawaya and Karen Smith-McCune of the University of California, San Francisco, said that while Gardasil appears to be safe and effective, "a cautious approach may be warranted" because of questions that still remain about the drug's long-term effectiveness and potential for adverse effects that could emerge over time. "Until we have the data, I view the situation as an ongoing experimental trial. The ultimate safety of the vaccine is unknown and it's going to be decades before we know anything,'' wrote the doctors.

The US giant’s share price only stuttered on the New York Stock Exchange yesterday, but investors will no doubt be sitting up and paying attention to this latest issue to beset Merck. The firm only relatively recently left a nadir following the global withdrawal of its one-time best selling agent Vioxx (rofecoxib) for arthritis, which was found to double the risk of heart attack when given for more than 18 months, reporting first quarter growth of 12% driven by its asthma agent Singulair (montelukast), as well as newer agents Januvia (sitagliptin) for diabetes and Gardasil. The latter reeled in $367 million in the first three months.