[Ip-health] AstraZeneca Pushes to Protect Crestor From Generic Competition

Thiru Balasubramaniam thiru at keionline.org
Mon Jul 11 02:12:18 PDT 2016



AstraZeneca Pushes to Protect Crestor From Generic Competition


JUNE 27, 2016

No more than a few hundred American children have a rare disease
characterized by ultrahigh levels of bad cholesterol.

Yet to the giant drug maker AstraZeneca, this small group could be worth
billions of dollars.

The company is making a bold attempt to fend off impending generic
competition to its best-selling drug, the anti-cholesterol pill Crestor, by
getting it approved to treat the rare disease. In an unusual legal
argument, the company says Crestor is entitled to seven years of additional
market exclusivity under the Orphan Drug Act, a three-decade-old law that
encourages pharmaceutical companies to develop treatments for rare diseases.

Critics say AstraZeneca is trying to abuse the law, since the overwhelming
use of Crestor is for treating adults with high cholesterol, not children
with the rare disease.

“This represents a deviation from the intent of the Orphan Drug Act,” said
Dr. Martin A. Makary, a professor of health policy at Johns Hopkins Medical
School. “It is now being used to dominate the market with retrofitted

Crestor, a cholesterol-lowering statin, was prescribed 20.3 million times
in the United States last year, the second-most of any brand-name drug
after Synthroid, a thyroid medicine, according to the prescription tracker
IMS Health. The drug, also known as rosuvastatin calcium, is scheduled to
lose patent protection on July 8, potentially exposing it to an onslaught
of generic competition.

The introduction of generics would weigh heavily on AstraZeneca’s bottom
line. Crestor is the company’s best-selling drug, accounting for $5 billion
of its $23.6 billion in product sales last year. About $2.8 billion in
sales were in the United States, where the retail price is about $260 a
month, according to GoodRx.com.

The chain of events leading up to the current controversy began in late
May, when AstraZeneca won approval of Crestor to treat children with the
rare disease, homozygousfamilial hypercholesterolemia, or HoFH. That
approval gave Crestor market exclusivity for seven years, though it applies
only to that disease.

One implication is that detailed prescribing information about using the
drug for the rare disease cannot be included on the label of generic
versions for seven years. However, the Food and Drug Administration can in
theory allow generics on the market for other uses, such as treating high
cholesterol in adults.

Yet AstraZeneca immediately petitioned the F.D.A., arguing that if the
correct dose for children with HoFH could not be on the generic label, then
it would be illegal and dangerous to approve any generic versions for any
use at all. That is because doctors might still prescribe the generic for
children with HoFH and choose the wrong dose, posing “substantial safety
and efficacy risks.”

Michele Meixell, a spokeswoman for AstraZeneca, said the company pursued
the new use of Crestor as “part of our standard practice to address unmet
needs.” She said the Orphan Drug Act “provides exclusivity as an incentive
for pharmaceutical companies to develop products to help address the needs
of an underserved patient population.”

It is far from certain that AstraZeneca’s argument will succeed, and it is
not known when the F.D.A. will decide. One response might be for the agency
to approve generic versions of Crestor on schedule, on July 8.

Spectrum Pharmaceuticals lost a lawsuit this month after trying in a
similar way to protect its cancer drug Fusilev from generic competition.

Otsuka Pharmaceutical recently tried a similar tactic to shield its
big-selling antipsychotic, Abilify, from generic competition by getting it
approved for a rare disease. The F.D.A. approved generics in April and its
decision was upheld in court.

Perhaps the most famous case was when Bristol-Myers Squibb tried for three
extra years of protection from generics for Glucophage, its big-selling
drug for adult-onsetdiabetes, by getting it approved to treat the
relatively few children with that disease. Outraged members of Congress,
calling the move an abuse of the system, amended the law in 2002 to
eliminate what came to be called the Glucophage loophole.

But Otsuka, in its recent court case, argued that lawmakers at that time
did not explicitly mention orphan exclusivity as a loophole to be closed.
The United States District judge hearing the case in Maryland, George J.
Hazel, dismissed that argument.

“It would defy logic,” he wrote, “to believe that in enacting this measure
to prevent a three-year exclusivity from becoming a ‘fundamental abuse of
the system’ that harmed consumers, Congress nonetheless intended to permit
the seven-year exclusivity Otsuka seeks here.”

In its petition to the F.D.A., AstraZeneca argues that the F.D.A. was
legally incorrect in the Otsuka case.

Kurt R. Karst, a director of the Washington law firm Hyman, Phelps &
McNamara and principal author of the FDA Law Blog said, “Given the Otsuka
precedent, it’s going to be an uphill battle” for AstraZeneca. He predicted
that the company would sue the F.D.A. if its request were denied.

While AstraZeneca has been studying use of Crestor for pediatric conditions
for some years, it began a clinical trial for children 6 to 17 years old
with HoFH only in 2014. About 300 to 1,000 people in the United States have
the disease, which involves two deleterious mutations, one from each
parent, said Katherine Wilemon, president of the FH Foundation, an advocacy
group. She said some people with the disease suffer heart attacks when they
are only 5 years old.

Michelle Watts of Hagerstown, Md., said that she and her husband, Jason,
both have high cholesterol, but, “We had no idea that we could both carry a
gene and there’s the possibility of us giving it to our children.”

Their 7-year-old daughter, Avery, has HoFH and already has some narrowing
of the arteries. She takes a generic statin and Zetia, another
anti-cholesterol pill. Every two weeks, the family drives three hours each
way for a treatment similar to dialysis, in which Avery’s blood is run
through a machine that cleanses it of cholesterol.

Mr. and Ms. Watts, who both use Crestor to treat their own high
cholesterol, declined to comment on AstraZeneca’s move, saying they did not
know enough about it.

AstraZeneca’s trial involved only 14 children and tested a single dose of
Crestor, according to the company’s petition. After six weeks of treatment,
those who took Crestor had a bigger decline in LDL, or bad cholesterol,
than those receiving a placebo. This result was expected, in that statins
like Crestor are already a cornerstone of treatment for such children.

Dr. Sidney M. Wolfe, founder and senior adviser of the Public Citizen
health research group, said that if AstraZeneca was interested in that rare
disease, “They could have done it a long time ago, not right before
midnight when it is about to turn into a pumpkin.”

One generic version of Crestor, sold by Allergan, reached the market in May
under a patent litigation settlement with AstraZeneca. But drug prices do
not typically plummet until there multiple generics are on the market.

The issue of using orphan diseases to give drugs extended protection from
generic competition is playing out on a bigger stage as well. A broad
pharmaceutical policy bill passed by the House of Representatives last
year, called the 21st Century Cures Act, would give six extra months of
protection from generic competition if an already marketed drug gets
approved for an orphan disease.

Max G. Bronstein, a senior director at the EveryLife Foundation for Rare
Diseases, an advocacy group, said the measure was backed by dozens of
patient groups because “repurposing” existing drugs is a quicker and less
costly way to get medicines approved for rare diseases than is developing
totally new drugs.

But Public Citizen predicted that the provision could add up to $12 billion
to the nation’s drug bill over 10 years because “cheaper generic versions
of drugs will be inaccessible to patients with much more common, nonorphan
diseases for an additional six months.”

The measure has not been passed by the Senate. Advocates hope it will be
added as an amendment to the Senate counterpart of the broader legislation.

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