Anyone
watching the anticholesterol market will start seeing
double soon as big pharmas bet increasingly on
combination pills to gain market share in the
world’s top-selling drug category. Building on the
remarkable success of Merck/Schering-Plough’s
Vytorin (Zetia with Zocor), the new pills will pair
top-selling statins with complementary compounds,
including some with new mechanisms.
The
question of “Who will control the biggest share of
the cholesterol-lowering market?” is one of the most
important facing the pharmaceutical industry. With
worldwide sales of more than $12 billion in 2005,
Pfizer’s Lipitor (atorvastatin) has long been the
“fairest” blockbuster of all. According to IMS
Health, the entire world market for “cholesterol and
triglyceride reducers” currently comprises a
whopping $32.4 billion. Now, that segment is set for a
facelift. Generics are already taking a big chunk of
traditional pharma’s profits. One answer is
combinations.
“If
you can combine effective therapeutics, you can
enhance efficacy and compliance,” says the Cleveland
Clinic’s Steven Nissen. The cholesterol-control
field is particularly ripe for this. “Combination
pills are the fastest-growing segment of the market
for lipidemia [i.e., anticholesterol],” says Abbott
vice president Eugene Sun.
It’s
not enough to throw two good drugs together. Vytorin
did a tidy $1 billion plus worldwide in 2005. On the
other hand, Pfizer’s Caduet (Norvasc [amlodipine
besyline] with Lipitor [atorvastatin calcium]) netted
less than $200 million that year. “I think the issue
with Caduet is that it treats two different diseases
— hypertension and lipid abnormalities,” says Sun.
“But doctors tend to look at different problems one
at a time.” In contrast, Vytorin mixes the
traditional statin, or HMG-CoA reductase inhibitor,
simvastatin with cholesterol absorption blocker
ezetimibe. Both mechanisms target lipidemia (See
“Finding the Magic in Fixed Combinations,”
Strategic Briefings, www.PharmaDD.com.)
The
key to success will be to really impact outcomes.
“Two drugs without outcomes just don’t give us
enough data,” says Nissen. But it is also clear that
while statins are very effective, there is plenty of
room to improve outcomes with new treatments.
Shall
We Dance?
AstraZeneca
(AZ) hopes to boost prospects for its Crestor, which
has so far disappointed. A recent study showed Crestor
is unique among statins because it actually reverses
the buildup of atherosclerotic plaque. (See JAMA,
April 5, 2006). Abbott and AZ are now jointly
developing a new pairing of Crestor with Abbott’s
fibrates Tricor and ABT-335. “They are
complementary,” says Peter Jones, of Baylor College
of Medicine. Statins are best at lowering LDL, while
fibrates are much better at raising HDL and lowering
triglycerides. That’s just the mix that should lower
heart disease risk. The Crestor/Tricor combination
could go up for approval by 2009.
Crestor
was initially hampered by safety concerns about
myopathy at higher doses. AZ is hoping that worry has
been quieted. “We’ve looked very carefully at
Crestor’s safety,” says Sun. “It does not have a
safety issue any different from other statins.”
Nonetheless, analysts have voiced concern that the
Crestor/Tricor combination could face the same
problem. Taken as separate pills, the combination
already carries a caution concerning muscular
toxicity.
Meanwhile,
Pfizer has sunk more than $800 million into testing a
combination of Lipitor with its own torcetrapib, which
could be the first cholesteryl ester transfer protein
(CETP) inhibitor to market. Hints of actual synergy,
or additive effects, are coming from that trial. In
another approach, Merck is developing a combination
product containing HDL-raising drug niacin with a
compound that will cut the bothersome facial flushing
niacin can cause. A form of that pill combined with
Zocor is also in testing; it is called MK-0524B.
AtheroGenics’
AGI-1067 is a totally new type of drug targeting the
inflammation underlying coronary artery disease. The
little company already has a partnership with AZ and
could be the spoiler in this competition. “Our
compound inhibits the inflammation irrespective of the
risk factor — hypertension, diabetes or anything
else,” says Russ Medford, CEO of AtheroGenics.
“The next advance in heart disease treatment will be
novel drugs paired with statins,” Medford
says. “We think ours is one of the more important of
the new drugs.”
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