By Toni Clarke
Feb 11 An advisory panel to the U.S. Food and
Drug Administration said on Tuesday that available evidence does
not prove that the painkiller naproxen, sold under the brand
names Aleve and Naprosyn, carries a lower cardiac risk than
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 and Celebrex.
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 continue.
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
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 also available.
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.
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