By Thomas M. Burton
SILVER SPRING, Md.--An epidemiologist with the Food and Drug
Administration on Monday laid out why the anti-inflammatory pain
drug naproxen may carry lower cardiovascular risks than comparable
drugs.
The epidemiologist, Dr. Andrew D. Mosholder, made the remarks at
a pivotal FDA advisory committee meeting here to determine whether
the agency will let drug makers differentiate the pain drugs'
labels based on their safety risks. Aleve is Bayer AG's brand name
for naproxen.
The FDA, based on Dr. Mosholder's work, has asked the panel
whether Aleve and generic naproxen should get a new label
highlighting lower heart risk than other drugs in the class like
Celebrex and ibuprofen, which go by brand names including Advil and
Motrin.
Dr. Mosholder, a reviewer in the FDA Division of Epidemiology,
said such heart risks are relatively lower with over-the-counter
versions of the drugs, compared to prescription versions, but that
the risks still are "observable" in some studies of OTC drugs.
He called the medical literature on the topic "a mile wide and
an inch deep," raising questions about whether the FDA can properly
differentiate among the medicines.
Dr. Mosholder also remarked that even naproxen in some studies
has been linked to small increases in cardiac events. "The results
across these studies are not uniform in all cases," he said.
Also at issue in the hearings is whether an FDA-ordered study
called Precision--which measures naproxen, ibuprofen and Celebrex
in seriously ill heart patients--will continue.
FDA-written analyses had suggested this study may no longer be
ethical in its current form if in fact naproxen truly is safer than
the other drugs.
After the 2005 hearings, the FDA asked Pfizer to sponsor
Precision, and about 22,000 patients had been enrolled as of
December 2013. The study is expected to be finished by next year.
It isn't considered ethical in medicine to randomly assign patients
to a treatment known less safe than others.
Dr. Steven E. Nissen, the principal investigator of Precision
and chairman of cardiovascular medicine at the Cleveland Clinic,
said the total number of cardiac events in his study "will dwarf
everything that has come before."
Referring to the data presented to the panel by the FDA, he told
the panel, "Most of what you looked at this morning were small
numbers of events." Thus, he said, if Precision is allowed by the
FDA to go to completion, it will likely lead to that a more
definitive answer about the relative safety of the drugs. The study
is expected to be completed by the end of 2015.
One study the FDA has focused on in a so-called meta-analysis,
or study of studies, from Oxford University in England.
"We're talking about relatively small hazards" with all the
drugs, said Oxford's Dr. Colin Baigent. "What we can't do is say
there's no risk with naproxen."
Pfizer, maker of Celebrex and Advil; and Johnson & Johnson,
Motrin's maker, said they are safe when used as directed and that
current labeling already reflects any cardiac risk the medicines
carry. Irene Laurora, a vice president in Bayer's consumer affairs
division, said naproxen "does not increase the risk" of heart
attack and stroke.
Write to Thomas M. Burton at tom.burton@wsj.com
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