Glaxo Downplayed Early Warning About AIDS Drug
7 CommentsBy Ed Silverman // May 12th, 2008 // 7:31 am
At issue is the risk of heart attacks that may be associated with its Ziagen med. Regulators recently began reviewing safety data after publication of a large observational study of more than 33,300 HIV patients, who are being followed to evaluate short- and long-term adverse effects of AIDS drugs.
However, Glaxo 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 Independent reports without citing sources.
The drugmaker also said that it could find no association between Ziagen and heart attacks following a review of internal data. However, Glaxo 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, the paper writes.
Some scientists monitoring the safety of AIDS drugs are angry with Glaxo for downplaying the significance of one of the biggest Ziagen safety trials when the findings were published, according to the Independent.
“GSK was extraordinarily well prepared in terms of a statement that downplayed the significance of the findings,” an unnamed scientist who was described as being close to the safety study tells the paper. “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.”
Alastair Benbow, Glaxo’s European medical director, tells the Independent that the drugmaker takes info about drug safety seriously, but didn’t want to highlight what may be “spurious observations” about Ziagen.
The first public sign that Ziagen may be linked with increased heart attack risk emerged this spring, when The Lancet published the worldwide “DAD” observational study, which found that the risk of having a heart attack in patients taking abacavir was almost double that of HIV patients who didn’t take the drug.
Independent scientists who analysed the DAD findings wrote in The Lancet that the data wasn’t strong enough to establish a causal connection because it would have required a different type of study, but added the observed increase in the risk of heart attacks was “too strong to ignore.” They also pointed out that the studies on which Glaxo relied for casting doubt on the DAD study were themselves not powerful enough to discount a link between Ziagen and heart attack risk.
To coincide with The Lancet publication, Glaxo issued a statement to its investors playing down the association between abacavir and heart attacks. The statement didn’t say Glaxo had been made aware three years earlier of a report involving 34 cases of heart attacks in patients taking Ziagenr. The report was sent to the company in May 2005 by the Uppsala Monitoring Centre in Sweden, the paper writes.
Didier Lapierre, Glaxo’s vp of clinical development, told investors last month 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,” she said, the paper writes.
The FDA and the European Medicines Agency so far say there is no reason to change the prescribing info. The risk didn’t appear to increase over time, but remained stable and appeared to be reversible after the meds were stopped, according to the FDA. Ziagen, by the way, is a nucleoside reverse transcriptase inhibitor, or NRTI. The analysis looked at relative risk among cumulative use, current use and past use.
Doc
“spurious observations” - here is one of my own.
“Didier Lapierre, Glaxo’s vp of clinical development, told investors last month that the increased relative risk of heart attacks remained low in absolute terms and that patients should not discontinue treatment without medical advice.”
- What a farce! Every pharma company I know of pushes their meds primarily based on Kaplan Mier Realtive Risk Reduction (RRR) curves. When challenged in the field by providers about low ‘absolute risk reduction’ (which is frequently less than overwhelming), the field sales forces are trained to discount the absolute risk reduction and emphasize the RRR of their product. Now when we see a pharma company on the hot seat for a distrubing trend in RRR, they discount that to focus on a low absolute risk reduction. If the general public could grasp what is being done in the name of ‘promotion’ and what ethical standard is selectively applied to rx drugs, what would they think?
truthma30
GSK is a market leader..
in downplaying dangerous side effects..
Paxil, Avandia and now Abacavir…
Well done GSK..
Bobby C
Does this really surprise anyone? To make money, pharmaceutical companies need to sell drugs.
To sell drugs, you have to downplay the side-effects.
This is a systemic problem, not unlike the steroid baseball scandal during the past decade.
It is corrupting medicine, it is corrupting science.
They have scared so many people into taking drugs — it’s placebo effect run amok. But, now the side-effects are so deadly and potent, it ain’t funny anymore.
When did medicine start causing heart attacks?
When did we casually accept the notion to fight fire with fire?
Just remember, it ain’t about your health. It’s about selling drugs.
HorusCat
Doc,
I talk about relative and absolute risk with my docs all the time, so I don’t have any idea what you are talking about. Many physicians don’t understand the difference–and especially as it applies to different disease states.
What is the baseline rate of MI in AIDS patients? How far along are they when the MI happens? What is their prognosis with and without the drug? What other outcome data does this drug have? Seems to me that these are far more important questions, and questions that I would ask were I to have AIDS.
HorusCat
Bobby C wrote:
“When did we casually accept the notion to fight fire with fire?”
Usually, one accepts that notion when one’s own ass is burning. Do you have AIDS? Those facing their imminent demise often are willing to take extreme measures to put that event off for a little while. Give the patients the facts and let them decide. I expect it will be like oncology and chemo–some go for it, some take a pass.
Bob Freeman
HorusCat, I think you’re right about relative and absolute risk. I teach pharmacoepidemiology (to pharmacy students and public health grad students) and have been surprised at the amound of remedial work I have to do for the entire class and for individuals. I’ve looked at the epi curriculum that med students get and it’s not emphasized to the extent one would think. Getting students to put in plain English what an odds ratio means is an “interesting” exercise.
HorusCat
Bob Freeman,
Not surprising. So I guess we shouldn’t be surprised when the American public is even more ignorant and reacts in hysterics to claims of this or that med “doubling” the risk of suicide, MI, toe fungus or whatever.
If people really understood risk, they wouldn’t drive anywhere, but they’d take their Celebrex to help them walk to the local store.