By Ron Winslow
The first of a powerful new class of cholesterol-lowering
medicines won approval from U.S. regulators Friday--a highly
anticipated medical advance that nevertheless promises to escalate
the growing clamor over drug costs.
The drug, called Praluent and developed by Regeneron
Pharmaceuticals Inc. and Sanofi SA, provides a new and in some
cases desperately needed option for several million high-risk heart
patients who can't get their cholesterol to desirable levels with
the blockbuster group of medicines known as statins.
But the companies are pricing the drug at $14,600 a year, an
especially high amount for a medicine aimed at a common condition
like heart disease. By contrast, statins, which are available in
generic versions and remain the mainstay drug option for
cholesterol reduction, can be purchased for just a few dollars a
month.
The approval by the U.S. Food and Drug Administration comes amid
a crescendo of concern over high drug prices. The $1,000-a-pill
price for Gilead Sciences Inc.'s hepatitis C drug Sovaldi triggered
outrage from pharmacy-benefit managers and government officials
worried about the impact on health programs such as Medicaid. Just
this week, more than 100 oncologists joined a growing chorus of
doctors lambasting the drug industry for cancer drug prices that
can reach $150,000 a year for individual patients.
Some experts say the new cholesterol agents could dwarf those
worries. "This could become the most expensive medication that we
use," said Troyen Brennan, executive vice president and chief
medical officer at CVS Health Corp., the pharmacy-benefits manager
and drugstore chain.
Unlike drugs for cancer or multiple sclerosis, which can have
six-figure annual price tags but are taken by relatively few
people, these new drugs could go to several million people. Adding
the price, plus the expectation that patients could stay on them
for 20 to 30 years, Dr. Brennan said, creates a multiplier effect
that could lead to a potential $50 billion to $100 billion-a-year
national tab.
Other projections are more tempered. Credit Suisse, for
instance, in a recent report that assumed a $10,000 price for the
drugs, predicted total peak annual sales of Praluent and two
expected rivals to eventually reach about $10 billion.
Regeneron and Sanofi defended Praluent's price. An antibody that
patients inject themselves, it will cost substantially less than
similarly administered drugs such as Humira and Enbrel for
rheumatoid arthritis and other autoimmune diseases, which are
prescribed for thousands of patients and which they said list for
more than $38,000 a year.
The toll in the U.S. for cardiovascular disease amounts to more
than $300 billion a year, according to estimates, while treating an
individual heart attack can range from $60,000 to $120,000, said
Leonard Schleifer, Regeneron's chief executive officer.
Expectations--not yet proven--are that the marked cholesterol
reductions seen with Praluent will translate into fewer deaths and
costly events.
The company believes "we've come up with a price that provides
value to the health-care system," Dr. Schleifer said.
After discounts drug makers routinely offer insurers and
government payers, the actual price will be lower than the list
price. And Praluent likely will soon have competition: A similar
drug, Repatha, from Amgen Inc., was approved in Europe early this
week, and the FDA's action date for a decision in the U.S. is Aug.
27. Pfizer Inc. has a candidate that could reach the market by
2017.
"It's not going to be the big shock to the system that other
people are predicting," said Elias Zerhouni, Sanofi's research
chief.
According to the FDA-approved label, Praluent is indicated for
patients with a hereditary condition called familial
hypercholesterolemia or with established coronary artery disease
and who need additional cholesterol lowering beyond aggressive
statin treatment to reduce their heart risk.
Regeneron says it believes between 8 million and 10 million
patients in the U.S. meet those criteria.
The new drugs represent the most significant advance against
cholesterol since the introduction of statins 28 years ago.
Statins, such as the blockbuster Lipitor, have transformed the
field of cardiology and contributed to sharp declines in the past
two decades in heart attacks and deaths from cardiovascular
disease.
Statins are taken by some 40 million Americans, and in addition
to a healthy diet and exercise remain the mainstay strategy to
lower LDL cholesterol, the chief culprit in the accumulation of
deposits in the coronary arteries that lead to heart attacks.
But a significant portion of patients are unable to control
their cholesterol with statins, either because they have
genetically high levels of LDL, or because they suffer side effects
such as muscle pain that make them statin intolerant, limiting or
precluding their ability to take the medicines.
Praluent works by blocking a protein called PCSK9, which
interferes with the body's ability to clear artery-damaging
cholesterol from the blood.
A series of genetic discoveries a decade ago laid the foundation
for Praluent and its rivals. After French researchers linked
mutations in the PCSK9 gene to high LDL levels and early heart
disease in French families, researchers Helen Hobbs and Jonathan
Cohen at University of Texas Southwestern Medical Center, Dallas,
wondered if other mutations might have the opposite effect.
They quickly found three candidates in the DNA of participants
in the medical center's 3,500-patient Dallas Heart Study who had
low LDL. Further research in a larger study revealed the mutations
were associated not only with lower LDL levels but with sharply
reduced risk of heart attacks and other serious problems.
"It told us we definitely had something important," Dr. Hobbs
said.
Then the researchers found a patient who had inherited two
copies of protective PCSK9 genes, essentially knocking out
production of the protein. The 32-year-old aerobics instructor's
LDL was an almost unheard of level of 14 mg/dl. She had two healthy
children and no obvious health problems.
The combination of low heart risk and apparent safety of very
low LDL was part of the package that persuaded companies to develop
antibodies to target PCSK9.
In clinical trials, Praluent has been shown to reduce LDL
cholesterol by 50% to 70% beyond that achieved with statins alone.
But whether that safely results in a commensurate reduction in
heart attacks and other consequences of heart disease won't be
known until results of a major long-term study are
reported--expected by 2017. Many observers expect adoption of the
drug to be modest at least until those data are known.
Doctors say between 5% and 20% of patients complain of muscle
pain from statins that leaves them statin-intolerant. Studies also
show the problem can often be overcome by changing statins or other
strategies. Insurers and pharmacy-benefits managers are already
planning to make sure heart patients exhaust their efforts to
control cholesterol with exercise, diet and statin drugs before
authorizing use of the new drugs.
"What makes this important is that this is such a huge market
that even a small fraction of the market is a large number," said
J. Sanford Schwartz, a professor of economics and of medicine at
University of Pennsylvania's Wharton School.
Write to Ron Winslow at ron.winslow@wsj.com
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