* Both drugs safely reduced artery-clogging plaque-study
* AstraZeneca was looking for clear edge for its Crestor
By Bill Berkrot and Lewis Krauskopf
ORLANDO, Fla., Nov 15 Pfizer Inc's
Lipitor and AstraZeneca's Crestor cholesterol drugs,
taken at their highest dose, safely reduced artery-clogging
plaque in heart patients, according to data from a clinical
trial presented on Tuesday.
Crestor outperformed Lipitor by some measures in the
two-year study, but it is unclear whether the results will help
AstraZeneca's sales force convince doctors and payers to use
its drug as it competes with much cheaper generic versions of
"The differences between the two drugs were modest," said
Dr. Stephen Nicholls, the primary investigator of the Saturn
study who presented the data at the American Heart Association
scientific meeting in Orlando.
Crestor has become AstraZeneca's biggest product, with
annual sales on pace to exceed of $6 billion this year, but its
growth and pricing are sure to be pressured by generic Lipitor,
AstraZeneca, which previously said its drug failed to show
a statistically significant advantage in the study's primary
plaque regression goal, was looking for a clear edge to
differentiate Crestor from its chief rival before Pfizer loses
U.S. exclusivity for Lipitor at the end of the month.
The results of the Saturn study may instead position
Crestor as more of a niche product for high-risk patients
unable to lower their cholesterol enough with other drugs.
"Clearly, generics have an important place, but there is an
important place also for Crestor as well," AstraZeneca Chief
Medical Officer Howard Hutchinson said.
While AstraZeneca's calculated bet to stand out when
compared with Lipitor may not pay off, the data was good news
for patients as both drugs reversed progression of heart
disease, and at the highest doses, from which doctors often shy
away over toxicity fears, proved to be safe taken for two
"What this study shows is that you can actually reverse the
buildup of plaque in a majority of patients with coronary
disease if you treat them very intensively with either of these
two powerful drugs," said Dr. Steven Nissen, chief of
cardiology at the Cleveland Clinic and the study's chairman.
Researchers found the safety seen with prolonged use of the
drugs at the highest dose to be particularly reassuring.
The rate of heart attacks, strokes and other major adverse
heart events were low for the patient population and nearly
identical for the two drugs -- 7.1 percent for Lipitor and 7.5
percent for Crestor.
"In these patients in whom you're seeing a lot of
regression they're not having events," Nicholls said.
"We were very struck by the fact that we could give over
1,000 patients the top doses of the most powerful statins and
basically we didn't hurt anybody," Nissen added.
The 24-month study completed by 1,039 heart patients taking
either 80 milligrams of Lipitor or 40 mgs of Crestor used
intravascular ultrasound (IVUS) to measure changes in atheroma
volume, or plaque buildup, inside a diseased artery.
The primary end point of the study was percentage change in
atheroma volume, which Crestor reduced by 1.22 percent and
Lipitor by 0.99 percent.
Researchers considered reductions from both drugs to be
clinically significant. But the difference between the two
medicines was not statistically significant and thus considered
a failure by Crestor to prove superiority.
In a secondary goal measuring total atheroma volume Crestor
did show a statistically significant advantage, reducing it by
6.4 cubic millimeters compared with a reduction of 4.4 cubic
millimeters for Lipitor.
By one measure between 65 percent and 71 percent of
patients in the study had plaque shrinkage.
"There were a lot of individuals who had regression of
disease and the degree of regression was quite profound,"
In terms of cholesterol levels, Crestor lowered bad LDL to
an average of 62.6 and raised good HDL to 50.4, while Lipitor
lowered LDL to 70.2 and raised HDL to 48.6. Current guidelines
call for LDL of 100 or lower and HDL of 40 or higher.
Crestor bested Lipitor on one safety measure with a
statistically significant advantage in liver enzyme elevation
of 0.7 percent versus 2 percent for Lipitor.
No serious muscle problems were observed with either drug,
"This notion that high dose statin therapy being
administered for 24 months was basically toxic to peoples'
muscles was not the case," Nicholls said.
AstraZeneca shares, which fell about 4 percent when the
initial result was announced in September, were up 0.3 percent
in London on Tuesday.