By Thomas M. Burton
A Food and Drug Administration advisory panel recommended that
the agency approve the cholesterol-lowering drug Praluent, the
first of a wave of such cardiovascular drugs expected to raise
billions of dollars in revenue and perhaps alter the treatment of
cardiovascular disease.
But many panelists said the use of the drug should be limited to
certain high-risk groups, such as people with very high cholesterol
for genetic reasons because of a condition called familial
hypercholesterolemia.
The committee voted 13-3 in favor of Praluent, from France's
Sanofi SA and Regeneron Pharmaceuticals Inc., of Tarrytown, N.Y.
But enough panelists expressed caution about the evidence in the
companies' studies, and so it may take longer than the industry
would like to get these medicines widely used.
Panel member Brendan M. Everett, director of the cardiology
inpatient service at Brigham and Women's Hospital in Boston, said
he would limit the drug's immediate use to certain patients with
genetic high cholesterol. "I would not allow broader use," Dr.
Everett said.
The new injectable medicine is administered every two weeks, and
is generically called alirocumab. It could help some patients who
can't tolerate or aren't effectively treated with statin drugs such
as Lipitor. Another such drug, Repatha from Amgen Inc., will go
before the panel on Wednesday.
The panel's recommendation late Tuesday boosted shares of
Sanofi, which was up 3% in after-hours trading at $50.92. Shares of
Regeneron had been halted in regular trading Tuesday pending
news.
This new class of medicines is often called PCSK9-inhibitors,
because they block a protein called PCSK9, which interferes with
the liver's ability to clear so-called bad cholesterol from the
bloodstream. That cholesterol, called LDL, is linked to cardiac
disease, albeit imperfectly.
Several members of the panel said that while statin drugs have
been shown to lower cholesterol and reduce cardiac disease, it's
not clear if these new PCSK9 drugs will do the same. "I don't
believe we have enough data today," said William R. Hiatt, a
cardiologist at the University of Colorado School of Medicine.
Statin drugs have been used by millions of people for more than two
decades.
The committee's chairman, Robert J. Smith of Brown University,
also expressed the wider concern among several panel members that
the effect of LDL "may be different for different patient
groups."
The two companies say they already have a study under way to see
if cardiac outcomes improve with the drug, and results are expected
in 2017.
The link between LDL and cardiac events like heart attack and
stroke isn't exact, although it has been shown to be significant in
a number of cardiovascular studies previously.
One impediment to use of the drug, if it should win FDA
approval, is its likely cost. Some Wall Street analysts say such
drugs could cost about $1,000 monthly.
The FDA doesn't always follow the recommendations of its
advisory committees, but generally does so.
In clinical studies evaluated by the FDA and advisory committee,
Praluent showed "no marked disparities in deaths, serious adverse
events or adverse events leading to discontinuation" of the drug,
wrote James P. Smith, deputy director of the FDA's division of
metabolism and endocrinology products in the agency's drug
center.
He wrote that there was some memory impairment in a greater
incidence of patients with Praluent than in comparison-group
patients, but that "was not characterized as serious" in the eight
patients reporting this reaction. Also, there were more liver
problems with Praluent, with 2.5% of patients suffering them,
compared with 1.8% on placebo.
Regarding the effectiveness of the drug, most of the studies
showed patients with the drug had their cholesterol lowered by
approximately 40% to 60%.
Reviewers for the FDA, in a report for the panel, said the drug
"demonstrates early and sustained" lowering of LDL cholesterol,
"regardless of background lipid-modifying therapies and is
generally well-tolerated."
Various members of the expert panel, while saying they were
overall comfortable with the data on the drug, expressed the
concern that studies so far hadn't gone on for long enough. Kenneth
D. Burman, a professor of medicine at Georgetown University and a
panel member, said "it seems probable that the drug will be safe
over time," but that, "We need longer-term studies."
Write to Thomas M. Burton at tom.burton@wsj.com
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