The recent withdrawal of
Merck's blockbuster COX-2 inhibitor, the anti-arthritis painreliever Vioxx
(rofecoxib), was a major blow to a number of interested parties: Merck, of
course, took the biggest hit. But the millions of arthritis sufferers who
depended on reliable and safe relief from pain since Vioxx's approval in
1999 are also confused and upset; and the federal drug regulators at the FDA
are in the midst of a losing streak of unprecedented proportions.
The FDA folks have come under increasing attack over the past few months. The
demand for allowing re-importation of cheaper drugs from Canada
has attained fever pitch, which the FDA has thus far resisted. Next came the
controversy over the safety of anti-depressants prescribed for children, with
some accusing the FDA of suppressing their own expert's comments. Then the
recent loss of half of America's flu vaccine due to sterility breakdowns at the
American-owned Chiron facility in Liverpool was alleged to have been due, in
part, to a failure of adequate FDA oversight -- now our CDC has been forced to
go scrounging the world for spare vaccine to protect our vulnerable elderly and
infirm.
Now, the Vioxx withdrawal, precipitated by Merck's own multi-year study,
designed not to assess cardiovascular risk, but to determine if the drug
prevents the onset of colon polyps in susceptible patients. This showed
evidence of an almost doubled risk of heart events or strokes after 18 months
of therapy. Merck made the tough decision to voluntarily withdraw the drug worldwide,
at least partially in fear of a torrent of liability lawsuits predicated on the
alleged adverse heart effects. Another reason, as stated by Merck, was the
continued availability of alternative COX-2 drugs. It seems likely that if Vioxx
were the only member of its class, some course of action short of complete
withdrawal would have been deemed appropriate -- such as a
"black-box" warning to physicians to avoid using it in patients with
possibly elevated heart risk.
Predictably, so-called "consumer" groups with 20/20 hindsight have
taken out their trusty retrospectroscopes -- the only medical instrument
guaranteed 100% accurate -- and condemned the FDA for not banning Vioxx
three years ago, when a preliminary study indicated a possible increase in cardiovascular
risk among patients taking the drug.
But these critics neglected to take into account the fact that Vioxx, as
with the other COX-2 drugs (Pfizer's Celebrex and Bextra), was
prescribed specifically to alleviate arthritis pain while posing less danger to
the stomach and GI tract. The older anti-arthritis drugs, known as NSAIDs, are
notorious for irritating the gut, sometimes causing bleeding severe enough to
require hospitalization. Among all classes of drugs, these were among the most
common causes of serious adverse drug reactions. Some estimates attribute over
10,000 deaths annually to NSAID complications. How many such complications have
been prevented by the use of Vioxx instead of one of the older NSAIDs?
No one can be sure, but the number is substantial. I practiced Rheumatology for
twenty years, and had to care for many patients suffering the ill effects of
NSAIDs -- there was no COX-2 option at that time.
Another valuable lesson gleaned from the Vioxx episode is the benefit to
consumers of "me-too" drugs, whose production and marketing has been
condemned in recent attacks on the pharmaceutical industry. No matter how
similar drugs may be in chemical structure, some patients will respond to one
and not another, while some will exhibit intolerance to one and not another.
Indeed, Merck itself hopes to launch another COX-2 inhibitor within the next
few months.
Some editorials went so far as to call for restrictions on the other COX-2
drugs, based on data from the Merck-Vioxx study alone. Yet, there is no solid
evidence incriminating the others in cardiovascular risk, only suspicion. While
those patients now on Celebrex and Bextra are concerned about the
potential risks to them as well, more studies should be done evaluating these
risks before restrictions are added.
No other anti-arthritis drug, including aspirin and the older NSAIDs, have been
studied over the length of time that Vioxx has been. Even aspirin would
not be approved for human use if it had to pass FDA evaluation today, due to its
propensity for inducing GI bleeding, allergic reactions, and blood thinning.
Indeed, while critics accuse the FDA of being lax, the opposite is true:
getting an innovative, life-saving pharmaceutical to market in the US
is an incredibly daunting, time-consuming and expensive endeavor.
The withdrawal of Vioxx may also mean that our progress toward reducing
the toll of colorectal cancer will be slowed. The results of the new
Merck-Vioxx study will soon be made public, but preliminary word indicates that
significant benefit in reducing the occurrence of pre-malignant colon polyps
was demonstrated.
What now will be the fate of this important drug? Hopefully, with appropriate
cautions, it can be resurrected as a chemopreventive agent against colorectal
cancer. Someday, it may again find a niche in selected arthritis sufferers with
low cardiovascular risk.
Gilbert Ross M.D. is Executive and Medical Director, The American Council on
Science and Health.
TCS Daily
Vioxx, We Hardly Knew Ye
By Gilbert Ross - October 20, 2004 12:00 AM
Categories:
Gilbert Ross