| In
2000,
according to IMS HEALTH's World
Review, cholesterol and triglyceride reducers
(C10A) were the world's second biggest therapy class,
with sales of $15.9 billion - up 21% from 1999.
The statins
make up the vast majority of the C10A class. The main
products are:
 |
Lipitor (atorvastatin), from Pfizer |
|
Zocor
(simvastatin), from Merck & Co |
|
Pravachol/Mevalotin
(pravastatin), from Bristol-Myers Squibb/Sankyo
|
|
Lipobay/Baycol
(cerivastatin), from Bayer |
|
Lescol
(fluvastatin), from Novartis |
|
Statin
sales 1997-2000
(12 months to December)
|
Source: MIDAS
(*Note - does not include sales of Mevalotin)
NB: 1997 figures do not include Czech Hospital, US
Home Health, or US Mail Order sales
Crestor
due in 2002
Lipitor has been the number one statin since the second
half of 1999, and has just overtaken Losec to become
the world's top selling pharmaceutical. If the trial
results detailed below lead to new indications for
any individual statins, it can only help them in the
ferocious battle for market share, which is about
to intensify.
At the American College of Cardiology conference held
in Orlando in March 2001, AstraZeneca
presented Phase III data for Crestor (rosuvastatin)
- the "superstatin" licensed from Shionogi. The results
showed that Crestor reduced LDL cholesterol by 40-58%,
and that it was more effective than Lipitor, Zocor
and Pravachol.
The established statin marketers did not take the
news lying down: a Pfizer senior medical director
commented, "I think it's a little too early for them
to say they're superior."
Trial results: Osteoporosis
In June 2000, The Lancet published the results of
a study from the US, which examined the relationship
between statin use and the risk of fracture in women
over 60. The research followed on from findings in
animals that statins can increase bone mineral density
(BMD) in the upper part of the thigh bone.
928 women who had suffered a fracture were compared
to 2,747 women who had not. It was found that the
women that had used statins at least 13 times in the
previous two years had a 52% decreased risk of
fractures.
Similar findings came from a UK study - 41 women taking
statins had 8% higher hip and spine BMD than
similar women not taking statins. The drugs may work
by stimulating the release of growth factors that
enhance the production of osteoblasts, the cells that
build bone. While the research was welcomed, those
involved cautioned that further work was needed. Indeed,
the largest trial in this area, the Women's Health
Initiative Observational Study, did not show a protective
effect.
Dementia
In November 2000, The Lancet included an article on
the effects of statins on the development of dementia.
Information was taken from 368 UK general practices.
All patients studied were over 50 and had received
lipid-lowering agents. It was found that those
who had been prescribed statins had a much lower risk
of dementia - estimated at 70%, but at least 37%.
Statins may work by keeping the blood vessels unclogged
with cholesterol, thus maintaining an adequate supply
of blood to the brain. Again, further research was
deemed necessary.
Heart disease
At the 73rd American Heart Association meeting, held
in November 2000, results were presented from the
MIRACL (Myocardial Ischemia Reduction
with Aggressive Cholesterol Lowering)
trial. This examined the effects of Lipobay/Baycol
(cerivastatin) on patients with unstable angina or
non-Q-wave myocardial infarction. Although cerivastatin
had a positive effect, the results were not statistically
significant and the MIRACL trial raised a number of
unanswered questions.
Bayer has now commenced PRINCESS (Prevention
of Re-INfarction by early treatment
of CErivaStatin Study) to address
these issues. This will examine whether cerivastatin
given immediately post-MI will prevent a second
cardiac event. 3,000 patients will be given cerivastatin
or a placebo within 48 hours of their MI and monitored
for two years. Cerivastatin may help in heart disease
by:
|
rapidly lowering levels of low-density lipoprotein
(LDL), leading to plaque stabilization |
|
reducing
inflammatory markers |
|
improving
endothelial function |
|
Also at the AHA meeting, findings were released from
a trial of 3,000 patients suffering from acute
coronary syndrome. Lipitor (atorvastatin)
led to a 16% decrease in the risk of death, heart
attack or severe ischemia in these patients. The
researchers said Lipitor should be used more often
immediately after an attack, when the risks of further
problems were highest.
This advice could also be taken from a Swedish study,
published in the Journal of the American Medical Association
in January 2001, which showed that starting heart
attack patients on statins immediately reduces
the risk of death by 25% over the next year. And
at the ACC meeting in March 2001, results were presented
which demonstrated that pravastatin reduced levels
of C-reactive protein, an important predictor
of heart disease risk.
Transplantation
The December 2000 edition of Nature Medicine included
a report on the in vitro effects of three statins
(Lipitor, Mevacor, and Pravachol)
on the immune system. Swiss researchers found that
the drugs suppressed the activation of helper T-cells,
and may thus have immunosuppressant effects
- useful in the treatment of transplant patients to
ward off organ rejection. Clinical studies will now
be needed to confirm the effects in humans.
Strokes
In January 2001, the AHA journal Circulation included
the results of the Prospective Pravastatin Pooling
Project, begun in 1992 and involving 19,768 participants.
This found that pravastatin reduced the incidence
of stroke by 20% in patients with heart disease
or high cholesterol levels. Pravastatin was most effective
in those with angina or who had already suffered a
heart attack.
Sankyo developed pravastatin and markets it as Mevalotin;
it is licensed to Bristol-Myers Squibb, which funded
the PPPP and uses the tradename Pravachol.
Diabetes
A sub-trial of the PPPP is WOSCOPS (West Of
Scotland COronary Prevention
Study). Involving 5,974 men, this was designed
to monitor the impact of pravastatin on the prevention
of a first heart attack in people with high cholesterol:
a positive effect was reported in 1995. A new analysis,
however (also published in Circulation), revealed
that pravastatin reduced the risk of developing
diabetes by 30%.
Further studies will be needed to confirm these findings
and to discover if it is a class effect of the statins
or unique to pravastatin. One such trial is already
underway: the Lipids in Diabetes Study will
recruit 5,000 patients and run for six years. It will
examine the effect of cerivastatin alone or
in combination with Fournier's Lipanthyl (fenofibrate)
on cardiovascular disease and death in Type II (adult-onset)
diabetics. |
