The panel was convened after a retrospective
analysis from multiple clinical trials published last year in The
Lancet suggested naproxen was less dangerous to the heart than other
nonsteroidal anti-inflammatory drugs, or NSAIDs, such as ibuprofen
Panelists recommended the FDA leave the current product labeling as
is, at least pending the outcome of a large ongoing study, known as
Precision, that compares naproxen with ibuprofen and Celebrex. The
FDA is not bound to follow the advice of its advisory panels, but
typically does so.
The FDA's final decision could have wide implications for the way in
which these drugs are prescribed and used in the future, and it will
have implications for whether the Precision trial is able to
The panel voted 16-9 that while the retrospective combining of
results from different studies, known as meta-analysis, hints at a
relative benefit for naproxen over other NSAIDs, the data is not
reliable and does not warrant changing the prescribing information
to reflect a differentiated risk.
"Meta-analyses are good for raising questions but not settling
them," said panelist Dr. Sanjay Kaul, a cardiologist and professor
at UCLA School of Medicine.
In 2005 the FDA determined that all NSAIDs should carry a warning
about cardiovascular risk but said there was no evidence that the
drugs carried different levels of risk. While the panel agreed that
more information has come to light since then, they are looking to
Precision to answer the question once and for all.
Naprosyn is a prescription product sold by Roche Holding AG, while
Aleve is sold over the counter by Bayer AG. Ibuprofen is marketed as
Advil by Pfizer Inc and Motrin by Johnson & Johnson. Celebrex is a
prescription product made by Pfizer.
Over-the-counter generic versions of both naproxen and ibuprofen are
One of the key questions in front of the panel was whether to modify
the Precision trial, which has been going on for seven years at the
request of the FDA. The trial is being funded by Pfizer and run by
the Cleveland Clinic.
[to top of second column]
Dr. Steven Nissen, chairman of the clinic's Department of
Cardiovascular Medicine and lead investigator on the Precision
study, told the panel the trial has enrolled nearly 27,000 patients,
more than 95 percent of the total needed, and that he expects it to
be complete around the end of 2015.
Precision is an academically directed trial whose scientific
governance resides with an unpaid independent executive committee,
Nissen said, and represents the best opportunity to date to answer
long-standing questions about the safety of NSAIDs that the FDA has
been wrestling with since the withdrawal of Merck & Co.'s Vioxx a
decade ago after it was linked to an increased risk of heart attack.
Dr. Garret FitzGerald, director of the Institute for Translational
Medicine and Therapeutics at the University of Pennsylvania who
helped craft the meta-analysis published in The Lancet, told the
panel that waiting for the Precision results would shed little light
on the relative risk of the drugs.
In the end, the panel recommended waiting for Precision and said
there should be no modification to the way the trial is being
(Reporting by Toni Clarke in Washington;
editing by Leslie Adler)
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