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GSK Responds to This Article: Glaxo 'downplayed' warning on heart-attack risk from Aids drug
  Monday, 12 May 2008
The multinational drugs company GlaxoSmithKline (GSK) downplayed an early warning about the rising number of people who have suffered heart attacks after using one of its drugs, abacavir. An anti-Aids medication, abacavir is taken by tens of thousands of people worldwide.
GSK was officially told of the possible risk in May 2005, three years before it issued a statement to its investors saying that the findings of an even stronger potential link between heart attacks and abacavir are "unexpected" and "unconfirmed". The company also said that it could find no association between abacavir use and heart attacks following a trawl through its internal data. However, it failed to mention that its own summary of product characteristics issued when the drug was launched in the late 1990s had described "mild myocardial degeneration" in mice and rats given the drug for two years.
In an interview with GSK, their response-- (from Jules: this is not explained properly, it's misinformation. In all the preclinical data there was no indication of a direct mechanism whereby abacavir could lead to an increased risk for myocardial infarction or ischemic heart disease. One the "mild myocardial degeneration" was caused by carbovir. Those studies were performed in mice and rats with carbovir. That is why abacavir, the pro-drug of carbavir, was invented. To avoid any cardiac issues associated with carbovir. Once abacavir was developed the same tox studies in animal tox studies typically done for developing a compound or drug and they did not see any cardiac signals at all in animal studies or in human studies with abacavir. The active metabolite of abacavir, carbovir, has been associated with cardiac fibrosis, but following a 600mg single dose of abacavir in humans the mean AUC ratio of carbovir:abacavir was 5.3% and myocardial degeneration or fibrosis would more likely lead to progressive congestive heart failure rather than myocardial ischema and infarction.)
Some scientists moni-toring the safety of Aids drugs are privately furious with GSK for downplaying the significance of one of the biggest safety trials of abacavir - one of several anti-virals taken by Aids patients in combined HIV therapy - when the findings were published last month.
"GSK was extraordinarily well prepared in terms of a statement that downplayed the significance of the findings," said a scientist close to the safety study. "As a consequence, people are confused. They think there is something wrong with the study because GSK said it cannot find evidence to support findings of a link with myocardial infarction [heart attack]."
Alastair Benbow, European medical director for GSK, said the company takes information about drug safety seriously but did not want to highlight what may be "spurious observations" about abacavir.
The first public sign that abacavir may be linked with increased heart attack risk emerged this April when The Lancet published the worldwide "DAD" study into adverse reactions to anti-HIV drugs after clinical observations of 33,347 Aids patients across Europe, Australia and the US.
The study found that the risk of having a heart attack in patients taking abacavir was almost double that of HIV patients who did not take the drug.
Independent scientists who analysed the DAD findings said in The Lancet that the data was not strong enough to establish a causal connection because that would have required a different type of study; but they said the observed increase in the risk of heart attacks was "too strong to ignore".
The same scientists also pointed out that the studies on which GSK relied for casting doubt on the DAD study were themselves not powerful enough to discount a link between the drug and heart attack risk.
To coincide with The Lancet publication, GSK issued a statement to its investors playing down the association between abacavir and heart attacks.
The statement did not say GSK had been made aware three years earlier of a report involving 34 cases of heart attacks in patients taking abacavir. The report or "signal" was sent to the company in May 2005 by the Uppsala Monitoring Centre in Uppsala, Sweden.
In response to my interview today (Jules Levin) GSK says that they did in fact submit their own internal data on abacavir, everything they had at the time. And the European regulatory agencies at that time said no action was warranted.
Didier Lapierre, GSK's vice-president of clinical development, said to investors at the time of the April DAD study that the increased relative risk of heart attacks remained low in absolute terms and that patients should not discontinue treatment without medical advice.
"The DAD findings are unexpected, since we have not seen similar findings in our studies, and we are unaware of any potential biological mechanism that would explain them. In our own analysis of trials involving more than 9,600 patients, no increased risk of heart attack associated with abacavir was found," Dr Lapierre said.
The US Federal Drug Administration and the European Medicines Agency have said that at present there is no reason to change the prescribing information for abacavir. But both are reviewing the safety data on the drug in relation to heart attacks.
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