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$1 Billion promo campaign to launch undertested, unproven drug.
THE LANCET
Volume 362, Number 9393
Tom McKillop is chief executive of AstraZeneca. He is widely respected
across the drug industry. The UK's
Academy of Medical Sciences elected him to its Fellowship in 2002, the
same year that he received a knighthood. Yet this glittering arc of
success is now
cast into shadow. For AstraZeneca's tactics in marketing its
cholesterol-lowering drug, rosuvastatin,raise disturbing questions
about how drugs enter clinical practice and what measures exist to
protect
patients from inadequately investigated medicines.
The statin market is vast. Pfizer's atorvastatin—the world's
best-selling drug—had sales in 2002 of US$ 8 billion. AstraZeneca
predicts that it can take a
20% share of this global market. It needs to. The company reported a
17% drop in pre-tax profits in the second quarter of this year. After
a damaging delay
over safety concerns, rosuvastatin finally won US FDA approval in
August and was launched last month, winning a 2% market share after
only three weeks.
McKillop has pledged to do whatever it takes to persuade doctors to
prescrib rosuvastatin, including launching an estimated $1 billion
first-year promotional
campaign. "We've got to drive the momentum",
he said at a recent investors meeting. "You get one shot at launching
a major new product. This is our shot."
The sales strategy for rosuvastatin is based around the Galaxy
programme. Galaxy is the contrived umbrella name for at least 16
clinical trials of wideranging
quality designed to investigate the efficacy of rosuvastatin in
various clinical settings. The trials within Galaxy have names to
match the company's cosmic intentions—Mercury, Stellar, Orbital,
Asteroid, Meteor, Jupiter, etc. With no clinical endpoint trial yet
completed, the company has chosen to market rosuvastatin by applying
adventurous statistics to an overinterpreted syllogism. The argument
is
familiar and seems compelling. First premise:
atherogenic lipid profiles cause atherosclerosis. Second premise:
atherosclerosis causes cardiovascular disease.
Conclusion: reversing atherogenic lipid profiles will reduce the risk
of heart disease. But AstraZeneca has
proceeded to push Galaxy into the realms of
astrological rather than astronomical logic.
Take one example. Stellar was a six-week, open label dose comparison
in 2268 patients with primary hypercholesterolaemia. Results were
recently reported in Current Medical Research and Opinions (2003; 19:
P1–P10). Rosuvastatin was compared with atorvastatin, simvastatin, and
pravastatin. AstraZeneca's drug was, dose for dose, more effective at
achieving national
guideline targets for lipid concentrations than its competitors. Based
on these tentative surrogate findings, one Stellar investigator, Peter
Jones, commented that, "If I have the option of achieving
goals at a lower comparable dose, I would choose that". This kind of
gloss does little to foster sensible, let alone critical, appraisal of
weak data. Similar twists in the statistical wind were reported
in a promotional supplement to the American Journal of Cardiology in
March this year by James Blasetto and colleagues. Blasetto, who works
for AstraZeneca in Wilmington, Delaware, combined soft end-point
data from five small 12-week trials to conclude with astonishing
certainty that rosuvastatin "can be of considerable value". It is
difficult to understand how
such blatant marketing dressed up as research can appear under the
name of a respected peer-reviewed
medical journal.
Why does the quality of debate about statins matter?
First, because safety cannot be assured. Bayer withdrew cerivastatin
in August, 2001, after the occurrence of unexpected cases of fatal
rhabdomyolysis.
The 80 mg dose of rosuvastatin was withdrawn
by AstraZeneca because of safety concerns. Some critics are even
anxious about the 40 mg dose. The finding of proteinuria and
microscopic haematuria
associated with rosuvastatin use are additional worries.
Second, talking up the efficacy of statins subverts efforts to conduct
large-scale outcome trials where they matter most—eg, in heart
failure. And third, given the beneficial results of mortality
end-point trials for other statins, what possible clinical
justification can there be for licensing an unproven statin?
Since there are no reliable data about efficacy and safety—and
AstraZeneca is facing unusually acute commercial pressure to force
rosuvastatin into the
market—doctors should pause before prescribing this drug. Physicians
must tell their patients the truth about rosuvastatin—that, compared
with its competitors, rosuvastatin has an inferior evidence
base supporting its safe use. AstraZeneca has pushed its marketing
machine too hard and too fast. It is time for McKillop to desist from
this unprincipled campaign.
The Lancet
The statin wars: why AstraZeneca must retreat
THE LANCET
Volume 362, Number 9393
THE LANCET
Volume 362, Number 9393
Tom McKillop is chief executive of AstraZeneca. He is widely respected
across the drug industry. The UK's
Academy of Medical Sciences elected him to its Fellowship in 2002, the
same year that he received a knighthood. Yet this glittering arc of
success is now
cast into shadow. For AstraZeneca's tactics in marketing its
cholesterol-lowering drug, rosuvastatin,raise disturbing questions
about how drugs enter clinical practice and what measures exist to
protect
patients from inadequately investigated medicines.
The statin market is vast. Pfizer's atorvastatin—the world's
best-selling drug—had sales in 2002 of US$ 8 billion. AstraZeneca
predicts that it can take a
20% share of this global market. It needs to. The company reported a
17% drop in pre-tax profits in the second quarter of this year. After
a damaging delay
over safety concerns, rosuvastatin finally won US FDA approval in
August and was launched last month, winning a 2% market share after
only three weeks.
McKillop has pledged to do whatever it takes to persuade doctors to
prescrib rosuvastatin, including launching an estimated $1 billion
first-year promotional
campaign. "We've got to drive the momentum",
he said at a recent investors meeting. "You get one shot at launching
a major new product. This is our shot."
The sales strategy for rosuvastatin is based around the Galaxy
programme. Galaxy is the contrived umbrella name for at least 16
clinical trials of wideranging
quality designed to investigate the efficacy of rosuvastatin in
various clinical settings. The trials within Galaxy have names to
match the company's cosmic intentions—Mercury, Stellar, Orbital,
Asteroid, Meteor, Jupiter, etc. With no clinical endpoint trial yet
completed, the company has chosen to market rosuvastatin by applying
adventurous statistics to an overinterpreted syllogism. The argument
is
familiar and seems compelling. First premise:
atherogenic lipid profiles cause atherosclerosis. Second premise:
atherosclerosis causes cardiovascular disease.
Conclusion: reversing atherogenic lipid profiles will reduce the risk
of heart disease. But AstraZeneca has
proceeded to push Galaxy into the realms of
astrological rather than astronomical logic.
Take one example. Stellar was a six-week, open label dose comparison
in 2268 patients with primary hypercholesterolaemia. Results were
recently reported in Current Medical Research and Opinions (2003; 19:
P1–P10). Rosuvastatin was compared with atorvastatin, simvastatin, and
pravastatin. AstraZeneca's drug was, dose for dose, more effective at
achieving national
guideline targets for lipid concentrations than its competitors. Based
on these tentative surrogate findings, one Stellar investigator, Peter
Jones, commented that, "If I have the option of achieving
goals at a lower comparable dose, I would choose that". This kind of
gloss does little to foster sensible, let alone critical, appraisal of
weak data. Similar twists in the statistical wind were reported
in a promotional supplement to the American Journal of Cardiology in
March this year by James Blasetto and colleagues. Blasetto, who works
for AstraZeneca in Wilmington, Delaware, combined soft end-point
data from five small 12-week trials to conclude with astonishing
certainty that rosuvastatin "can be of considerable value". It is
difficult to understand how
such blatant marketing dressed up as research can appear under the
name of a respected peer-reviewed
medical journal.
Why does the quality of debate about statins matter?
First, because safety cannot be assured. Bayer withdrew cerivastatin
in August, 2001, after the occurrence of unexpected cases of fatal
rhabdomyolysis.
The 80 mg dose of rosuvastatin was withdrawn
by AstraZeneca because of safety concerns. Some critics are even
anxious about the 40 mg dose. The finding of proteinuria and
microscopic haematuria
associated with rosuvastatin use are additional worries.
Second, talking up the efficacy of statins subverts efforts to conduct
large-scale outcome trials where they matter most—eg, in heart
failure. And third, given the beneficial results of mortality
end-point trials for other statins, what possible clinical
justification can there be for licensing an unproven statin?
Since there are no reliable data about efficacy and safety—and
AstraZeneca is facing unusually acute commercial pressure to force
rosuvastatin into the
market—doctors should pause before prescribing this drug. Physicians
must tell their patients the truth about rosuvastatin—that, compared
with its competitors, rosuvastatin has an inferior evidence
base supporting its safe use. AstraZeneca has pushed its marketing
machine too hard and too fast. It is time for McKillop to desist from
this unprincipled campaign.
The Lancet
The statin wars: why AstraZeneca must retreat
THE LANCET
Volume 362, Number 9393